AUTHOR OF THIS BLOG

DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER

Angiotensin-I-Converting Enzyme (ACE) Inhibitors from Marine Resources: Prospects in the Pharmaceutical Industry

 Uncategorized  Comments Off on Angiotensin-I-Converting Enzyme (ACE) Inhibitors from Marine Resources: Prospects in the Pharmaceutical Industry
Feb 202015
 

 

 

 

Mar. Drugs 2010, 8(4), 1080-1093; doi:10.3390/md8041080

Review
Angiotensin-I-Converting Enzyme (ACE) Inhibitors from Marine Resources: Prospects in the Pharmaceutical Industry
Isuru Wijesekara 1 and Se-Kwon Kim 1,2,*
1
Marine Biochemistry Laboratory, Department of Chemistry, Pukyong National University, Busan 608-737, Korea; E-Mail: isurumatara@yahoo.com (I.W.)
2
Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Korea
*Author to whom correspondence should be addressed; E-Mail: sknkim@pknu.ac.kr; Tel.: +82-51-629-7094; Fax: +82-51-629-7099.
Received: 19 February 2010; in revised form: 8 March 2010 / Accepted: 29 March 2010 /
Published: 31 March 2010

Abstract

: Hypertension or high blood pressure is one of the major independent risk factors for cardiovascular diseases. Angiotensin-I-converting enzyme (EC 3.4.15.1; ACE) plays an important physiological role in regulation of blood pressure by converting angiotensin I to angiotensin II, a potent vasoconstrictor. Therefore, the inhibition of ACE activity is a major target in the prevention of hypertension. Recently, the search for natural ACE inhibitors as alternatives to synthetic drugs is of great interest to prevent several side effects and a number of novel compounds such as bioactive peptides, chitooligosaccharide derivatives (COS) and phlorotannins have been derived from marine organisms as potential ACE inhibitors. These inhibitory derivatives can be developed as nutraceuticals and pharmaceuticals with potential to prevent hypertension. Hence, the aim of this review is to discuss the marine-derived ACE inhibitors and their future prospects as novel therapeutic drug candidates for treat hypertension.

– See more at: http://www.mdpi.com/1660-3397/8/4/1080/htm#sthash.B8fUm0Hw.dpuf

 

 

सुकून उतना ही देना प्रभू, जितने से
जिंदगी चल जाये।
औकात बस इतनी देना,
कि औरों का भला हो जाये।

 COCK WILL TEACH YOU

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO …..FOR BLOG HOME CLICK HERE
Join me on Linkedin

View Anthony Melvin Crasto Ph.D's profile on LinkedIn

Join me on Facebook FACEBOOK
Join me on twitterFollow amcrasto on Twitter
Join me on google plus Googleplus

 

 amcrasto@gmail.com

 

 

 

 

 

Share

Vinita Gupta, Group President and CEO at Lupin Pharmaceuticals

 Uncategorized  Comments Off on Vinita Gupta, Group President and CEO at Lupin Pharmaceuticals
Feb 192015
 

Vinita Gupta, 43, Group President and CEO, Lupin Pharmaceuticals and Director, Lupin

Feb 2015….India-based drugmaker Lupin has signed an agreement with Polish biopharmaceutical firm Celon Pharma to develop a fluticasone / salmeterol dry powder inhaler (DPI).

Under the deal, Lupin will take the responsibility for commercialisation of the product, which is a generic version of GlaxoSmithKline’s (GSK) Advair Diskus.

Lupin CEO Vinita Gupta said: “We are very pleased to partner with Celon given their experience in the development and manufacturing of fluticasone/salmeterol DPI in Europe…………..http://www.pharmaceutical-technology.com/news/newslupin-celon-pharma-partner-generic-version-gsks-advair-diskus-4514718?WT.mc_id=DN_News

 

Ms. Vinita Gupta is the CEO of Lupin Pharmaceuticals Inc, USA, (LPI) and Group President, Director on the board of Lupin Limited and a Director on the Board of Lupin’s Japanese subsidiary Kyowa Pharmaceuticals.  Ms. Gupta is responsible for the North American and European business of the company.

Ms. Gupta joined Lupin in 1992 and developed Lupin’s entry strategy into US and Europe.  Under her leadership Lupin has emerged as a leader in the US generic market as well as the only company from India to have a successful brand business in the US.  As part of her responsibility she built the entire management team for the US and European business and supervised the development of the company’s pipeline.

Ms. Gupta holds a Bachelor’s degree in Pharmacy from the University of Mumbai and MBA from J L Kellogg Graduate School of Management, Northwestern University.

“A good year” is how Vinita Gupta, Group President and CEO at Lupin Pharmaceuticals, describes her company’s performance at a time when unsettling news was the key takeaway for pharma companies. Lupin grew by an impressive 35.9 per cent globally and 24 per cent in India. New product launches helped it grow its generics business by 52 per cent, making it the sixth-largest generics pharmaceutical company globally by market capitalisation and the third-largest Indian pharmaceutical company by revenues. “I can’t think of any challenges that affected Lupin’s performance during the last fiscal year,” says Gupta, 44. The company’s strategy now is to focus strongly on building its branded business globally.

 

 

Vinita Gupta, 43, Group President and CEO, Lupin Pharmaceuticals and Director, Lupin, is based in the United States, but has been in India a lot in the past one year.

Vinita Gupta, 43, Group President and CEO, Lupin Pharmaceuticals and Director, Lupin,
Vinita Gupta

With an expanding role in Lupin’s universe, Vinita has been spending more time outside the US, at times taking her six-year-old son, Krish with her. “He is getting exposure at a much younger age,” she says. Gupta herself was exposed to business at the age of 11 by her father Desh Bandhu Gupta, Lupin’s founder and Chairman.

“We almost had a family board at home, discussing work,” she says. Currently work goes well indeed, with Gupta taking new initiatives in India and also making the business more global. “I am focusing on drivers for growth in our business for the next five years,” she says.

Gupta is married to US-based businessman Brij Sharma.

She was 13 when she travelled to Switzerland with her father, to watch him position the family-run Lupin Limited, to negotiate and to strategise. It was enough to get her hooked. Enough for her to move away from a childhood fascination for art and enter the world of pharmaceuticals. Group president and CEO, Lupin Pharmaceuticals, and director on the board of Lupin Limited, Vinita Gupta has never regretted that decision. The 41-year-old is responsible for creating a substantial international presence for the company that was born in Mumbai in 1968 and named after a leguminous flower.

The Lupin group produces affordable generic and branded formulations in the world with a significant presence in cardiovasculars, diabetes, asthma, pediatrics and anti-infectives. But Desh Bandhu Gupta, her father, wanted the company to make an impact in the western market.

It was a challenge that seemed perfect for Gupta who graduated in pharmacy from the University of Mumbai and then spent a year working at the company in Mumbai. She then moved to the US for an MBA from the J.L. Kellogg Graduate School of Management at Northwestern University, following it with a brief stint in a US pharma company. But she didn’t want to be a mere “cog in the wheel”, returning to India to take up that initial challenge-to create a business strategy that would allow Lupin to enter American and European markets.

Today, Lupin is the ninth largest generics company in the US. It is also one of India’s top five pharmaceutical players and one of the fastest growing top 10 generic players in Japan and South Africa. The US arm of the business, Gupta’s baby, contributes to over 30 per cent of Lupin’s revenues, a company that clocked in close to Rs.4,000 crore in 2008-2009. Nine out of the 23 generic products Lupin has in the US market are at the number one position giving consistent competition to larger US pharma companies.

With brother Nilesh

 

 

 

 

 

With brother NileshThe beginning however was difficult. After all, India wasn’t very well known in the US market. “We realised that we had the aspirations but not the infrastructure in the form of facilities to meet US and European requirements and standards,” she remembers. So she spent three years building the infrastructure, creating a process that would be acceptable to these regulated markets. The break came with Suprax, a pediatric antiinfective drug that was valued at nearly $60 million in the US market. Gupta had already filed for a generic of the brand. “Suddenly, we had the opportunity to brand the generic, so we licensed the brand name from the innovator as he had left the market,” she remembers. It was a three-person team with 40 outsourced sales people.

Today, the product’s sales are at $74 million. It has been satisfying, she says. “The innovator was in the market with a sales force of 300 people. We are 60.” The aim, she says, has always been to balance branded products as well as generic. The success, her father and chairman of the company, Desh Bandhu Gupta, says, stems not just from her determination. “It’s also her intimate understanding of the entire pharma spectrum with the motivation to see it through,” he says.
This determination became obvious when she managed to persuade the dean at Kellogg to give her admission, even though she was 19 and perhaps the youngest in her class. It was a challenging time as she learned to balance her work and household chores. “At that time in India, everything was handwritten. I had to do every single thing using the computer,” says Gupta who often bribed her friends with homemade Indian food to type out her projects. It taught her to be independent.

But it was perhaps, two months ago, when Gupta a bigger challenge. A deal that made tough seem an understatement. For Antara, an anti-cholesterol drug. “It was very much like Suprax, that was serendipity,” says Gupta. It was a large product with high potential. But the company was in bankruptcy. “I was sure we could do things differently with the product,” she says.

Gupta says Lupin was the first to file for the generic brand. But they couldn’t own the generic and the brand. She had six weeks to sell the generic, win the bid in the US bankruptcy court and buy the brand. She did it. At $38 million, one-third its market value. It’s a deal that Nilesh, her brother and group president and executive director, believes displayed his sister’s meticulous calibre. “There were three sets of negotiations going on at the same time. And while there were others involved, this deal was Vinita all the way,” he says.

Kamal Sharma, managing director, Lupin Limited, has watched Gupta transform from a teenager learning the ropes of a business to the successful go-getter that she is today. “She values, teaches and encourages her people to deliver consistent results year after year,” he says. It’s an attitude that is apparent from the get-go.

(L-R) With Richa, Kavita, Anuja and Nilesh

 

 

 

 

(L-R) With Richa, Kavita, Anuja and NileshAt the Trident, Mumbai, for the photo shoot, Gupta is comfortable surrounded by people, even though she is a little hesitant in front of the camera. It’s here that she actually seems to shed the image of an ultimate powerhouse, a businesswoman driven to succeed. It is here that she becomes the Mumbaikar who prefers a masala chai over brewed coffee and a plain tee over a designer label. In some ways, she is still the girl who grew up in a housing society near the airport in Vile Parle, Mumbai. It’s the kind of place where people still keep their doors open and where one can walk into a neighbour’s house without having to knock. Things weren’t handed to her on a golden platter, she admits. In fact, she says, their father taught them that, “as a family we would have to work harder to earn and deserve our right more than what other professionals do.”

As a child, she remembers sharing a room with her four siblings, Kavita, Anuja, Nilesh and Richa. She didn’t like that very much. “But now, when I think of it, I feel it was an amazing life,” she says. Her father adds that he always took his children to different countries, either on work or otherwise. It was his way of showing them the world and different experiences.
But a different side emerges as Gupta talks of the pharma industry. “I dreamed of taking what Dad had built and adding value to it in the western markets,” she says. “This is what I had always prepared myself for. I am living the dream.” And it isn’t as if there aren’t any downs. Six months ago, she remembers, the company received a warning letter from the Food and Drug Administration. She spent that time working to resolve their concerns. “And then three months later, we made one of our most attractive acquisitions. The industry is so quick changing, so dynamic. It always keeps you thinking,” she says.

For Nilesh though, Gupta is his sounding board, the eldest sister with whom he shares a relationship that complements their work profiles. And while Nilesh says with a laugh, Gupta doesn’t pull the bigsister act with him at work, home is a different story. Gupta admits with a mock sigh, “You can’t posture with your siblings. You can posture with anyone else, but not your siblings.”

With husband Brij and son Krish

 

 

 

 

 

 

With husband Brij and son KrishThe obvious downside, however, is family. Her work keeps her busy, sees her up and in office by 8 am, back just in time to spend about an hour with her four-year-old son Krish. “He was a very easy child till some time ago, but lately he has become very demanding,” she says with a smile. Just as Gupta was leaving her home in Baltimore, Maryland for her current trip to India, Krish demanded they go leaf-picking in their backyard. “More than anything, I loved watching the expression on his face while we were picking leaves. His smile brightens up my day,” she says.

As much as her job is a passion she tries to spend time with Krish and husband Brij Sharma, a businessman whom she met in the US. “My husband is a very good listener. I keep talking whenever I am with him and he listens even today,” she says with a laugh. A workout is a must, however, as Gupta heads to the gym every day, spinning the cycle even when she was eight months pregnant.

“My husband jokes that’s the reason why Krish thinks and behaves ahead of his age,” laughs Gupta. But biking near the waterfront with her son and spending time on her husband’s boat is an activity that wins hands down. As does time spent with her two sisters Anuja and Richa, who live in Chicago. While Anuja is a pediatric cardiologist, Anuja is into public health. They do plan vacations together, but she often discovers that her brother Nilesh refuses to talk to her over the weekend. “Probably because I always end up talking about work,” she says with a laugh. “It has become so much a part of our lives,” she says.

Biggest Challenge

To bring in the changes required that will continue to set the company apart from the competition, and to attain a good work-life balance

In June2012 , Vinita Gupta, CEO of Lupin Pharmaceuticals Inc, the Indian drug maker’s US unit, received the “Entrepreneur of the Year” award from Ernst & Young in the health services and technology category for Maryland state of the US. Over the past year, the US business of Lupin crossed the $500 million mark.

ms-vinita-gupta-ceo-lupin-pharma-winner-of-the-e-y-entrepreneur-of-the-year-2012-award Ms Vinita Gupta, CEO, Lupin Pharma – Winner of the E&Y Entrepreneur of the Year 2012 Award Singapore: Ernst & Young LLP have awarded the Entrepreneur of the Year 2012 Award in the Health Services and Technology category to Ms Vinita Gupta, CEO, Lupin Pharmaceuticals. As a Maryland award winner, Ms Gupta is now eligible for consideration for the National Entrepreneur of the Year 2012 Award. The award recognizes outstanding entrepreneurs, who demonstrate excellence and extraordinary success in such areas as innovation, financial performance and personal commitment to their businesses and communities. Ms Gupta was selected by an independent panel of judges, and the award was presented at a special gala on June 28, 2012, at the Baltimore Marriott Waterfront, Maryland. Commenting on the award, Ms Vinita Gupta, CEO, Lupin Pharmaceuticals said, “I am honored to receive this recognition on behalf of our company. We have been very fortunate to have multiple opportunities to grow and differentiate our organization while bringing quality, affordable generics and valuable brands to the US market. The passion, dedication and entrepreneurial spirit of our team has set us apart from competition.”

DB Gupta (centre) Chairman, Vinita Gupta (right) CEO and Nilesh Gupta

Share

Large-Scale Continuous Flow Transformation of Oximes into Fused-Bicyclic Isoxazolidines: An Example of Process Intensification

 Uncategorized  Comments Off on Large-Scale Continuous Flow Transformation of Oximes into Fused-Bicyclic Isoxazolidines: An Example of Process Intensification
Feb 122015
 

Abstract Image

Here, we report a continuous flow protocol for the [3 + 2] cycloaddition of nitrones, in situ generated from oximes, into bicyclic isoxazolidines. This thermal process required very high temperatures to be efficient that were not easily reached in conventional reactors. A couple of examples are presented and in both the flow process showed a greater performance than the batch mode. The process intensification study allowed the generation of 120 g/h of a key pharmaceutical intermediate.

Large-Scale Continuous Flow Transformation of Oximes into Fused-Bicyclic Isoxazolidines: An Example of Process Intensification

see

http://pubs.acs.org/doi/abs/10.1021/op500350y

† Centro de Investigación Lilly S.A., Avda. de la Industria 30, Alcobendas-Madrid 28108, Spain
‡ Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285,United States
Org. Process Res. Dev., Article ASAP
DOI: 10.1021/op500350y
Publication Date (Web): January 28, 2015
Copyright © 2015 American Chemical Society

Share

A Green and Sustainable Approach: Celebrating the 30th Anniversary of the Asymmetric l-Menthol Process

 MANUFACTURING, SYNTHESIS, Uncategorized  Comments Off on A Green and Sustainable Approach: Celebrating the 30th Anniversary of the Asymmetric l-Menthol Process
Feb 052015
 

A Green and Sustainable Approach: Celebrating the 30th Anniversary of the Asymmetric l-Menthol Process 

Takasago has been devoted to producing l-menthol since 1954, and our long history of manufacturing this important aroma chemical is reviewed here. The current asymmetric catalytic process had its 30th anniversary in 2013. Our l-menthol process is considered carbon-neutral, and, therefore, ‘green’ and sustainable. It uses renewable myrcene obtained from gum rosin as a starting material. In addition, the Rh-BINAP (=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) catalytic system is highly efficient. This pathway not only leads l-menthol, but a variety of 100% biobased aroma chemical products as well. By measuring the 14C levels in a material, one can determine the percentage of carbon that is biobased. This biobased assay, described as the ratio plant-derived C/fossil-derived C, can clarify how renewable a product really is. This will be highlighted for several of Takasago’s key aroma chemicals.

A Green and Sustainable Approach: Celebrating the 30th Anniversary of the Asymmetric l-Menthol Process

  1. Makoto Emura* and
  2. Hiroyuki Matsuda

Article first published online: 18 NOV 2014

DOI: 10.1002/cbdv.201400063

Issue

Chemistry & Biodiversity

Chemistry & Biodiversity

Volume 11, Issue 11, pages 1688–1699, November 2014

http://onlinelibrary.wiley.com/doi/10.1002/cbdv.201400063/abstract

 

 

Production

As with many widely used natural products, the demand for menthol greatly exceeds the supply from natural sources. In the case of menthol it is also interesting to note that comparative analysis of the total life-cycle costs from a sustainability perspective, has shown that production from natural sources actually results in consumption of more fossil fuel, produces more carbon dioxide effluent and has more environmental impact than either of the main synthetic production routes.[7]

Menthol is manufactured as a single enantiomer (94% ee) on the scale of 3,000 tons per year by Takasago International Corporation.[8] The process involves an asymmetric synthesis developed by a team led by Ryōji Noyori, who won the 2001 Nobel Prize for Chemistry in recognition of his work on this process:

Myrcene Diethylamine Citronellal Zinc bromide

Menthol synthesis.png

About this image

The process begins by forming an allylic amine from myrcene, which undergoes asymmetric isomerisation in the presence of a BINAP rhodium complex to give (after hydrolysis) enantiomerically pure R–citronellal. This is cyclised by a carbonyl-ene-reaction initiated by zinc bromide to isopulegol, which is then hydrogenated to give pure (1R,2S,5R)-menthol.

Another commercial process is the Haarmann-Reimer process. [9][10] This process starts from m-cresol which is alkylated with propene to thymol. This compound is hydrogenatedin the next step. Racemic menthol is isolated by fractional distillation. The enantiomers are separated by chiral resolution in reaction with methyl benzoate, selective crystallisation followed by hydrolysis.

synthetic menthol production

Racemic menthol can also be formed by hydrogenation of pulegone. In both cases with further processing (crystallizative entrainment resolution of the menthyl benzoate conglomerate) it is possible to concentrate the L enantiomer, however this tends to be less efficient, although the higher processing costs may be offset by lower raw material costs. A further advantage of this process is that d-menthol becomes inexpensively available for use as a chiral auxiliary, along with the more usual l-antipode.[7]

References

  1. R. Eccles (1994). “Menthol and Related Cooling Compounds”. J. Pharm. Pharmacol. 46 (8): 618–630. PMID 7529306.
  2.  Galeottia, N., Mannellia, L. D. C., Mazzantib, G., Bartolinia, A., Ghelardini, C.; Di Cesare Mannelli; Mazzanti; Bartolini; Ghelardini (2002). “Menthol: a natural analgesic compound”.Neuroscience Letters 322 (3): 145–148. doi:10.1016/S0304-3940(01)02527-7. PMID 11897159.
  3.  G. Haeseler, D. Maue, J. Grosskreutz, J. Bufler, B. Nentwig, S. Piepenbrock, R. Dengler and M. Leuwer. (2002). “Voltage-dependent block of neuronal and skeletal muscle sodium channels by thymol and menthol”. European Journal of Anaesthesiology 19 (8): 571–579. doi:10.1017/S0265021502000923.
  4. Brain KR, Green DM, Dykes PJ, Marks R, Bola TS; Green; Dykes; Marks; Bola (2006). “The role of menthol in skin penetration from topical formulations of ibuprofen 5% in vivo”. Skin Pharmacol Physiol 19 (1): 17–21. doi:10.1159/000089139. PMID 16247245.
  5. PDR for Herbal Medicines (4th ed.). Thomson Healthcare. p. 640. ISBN 978-1-56363-678-3.
  6. Croteau, R. B.; Davis, E.M.; Ringer, K. L; Wildung, M. R. (December 2005). “(−)-Menthol biosynthesis and molecular genetics”. Naturwissenschaften 92 (12): 562–77.Bibcode:2005NW…..92..562C. doi:10.1007/s00114-005-0055-0. PMID 16292524.
  7. Charles Sell (ed.). The Chemistry of Fragrances: From Perfumer to Consumer. ISBN 978-085404-824-3.
  8.  Japan: Takasago to Expand L-Menthol Production in Iwata Plant
  9.  After the company Haarmann & Reimer , now part of Symrise
  10. Schäfer, Bernd (2013). “Menthol”. Chemie in unserer Zeit 47 (3): 174. doi:10.1002/ciuz.201300599.
Share

TRIPS Agreement

 PATENTS, Uncategorized  Comments Off on TRIPS Agreement
Jan 232015
 
World Trade Organization Members.svg

  WTO members (where the TRIPS agreement applies)
  Parties to the Agreement where also the membership of the European Union applies
“TRIPS” redirects here. For the microprocessor, see TRIPS architecture. For the German racing driver, see Wolfgang von Trips. For other uses, see Trip.
TRIPS Agreement
Annex 1C to the Agreement establishing the World Trade Organization
Agreement on Trade-Related Aspects of Intellectual Property Rights
World Trade Organization Members.svg

  WTO members (where the TRIPS agreement applies)
  Parties to the Agreement where also the membership of the European Union applies
Type Annex to the Agreement establishing the World Trade Organization
Effective 1 January 1996
Parties 158 (All WTO members)[1]
Languages English, French and Spanish
 Agreement on Trade-Related Aspects of Intellectual Property Rights at Wikisource

 

 

 

The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) is an international agreement administered by the World Trade Organization (WTO) that sets down minimum standards for many forms of intellectual property (IP) regulation as applied to nationals of other WTO Members.[2] It was negotiated at the end of the Uruguay Round of the General Agreement on Tariffs and Trade (GATT) in 1994.

The TRIPS agreement introduced intellectual property law into the international trading system for the first time and remains the most comprehensive international agreement on intellectual property to date. In 2001, developing countries, concerned that developed countries were insisting on an overly narrow reading of TRIPS, initiated a round of talks that resulted in the Doha Declaration. The Doha declaration is a WTO statement that clarifies the scope of TRIPS, stating for example that TRIPS can and should be interpreted in light of the goal “to promote access to medicines for all.”

Specifically, TRIPS requires WTO members to provide copyright rights, covering content producers including performers, producers of sound recordings and broadcasting organizations; geographical indications, including appellations of origin; industrial designs;integrated circuit layout-designs; patents; new plant varieties; trademarks; trade dress; and undisclosed or confidential information. TRIPS also specifies enforcement procedures, remedies, and dispute resolution procedures. Protection and enforcement of all intellectual property rights shall meet the objectives to contribute to the promotion of technological innovation and to the transfer and dissemination of technology, to the mutual advantage of producers and users of technological knowledge and in a manner conducive to social and economic welfare, and to a balance of rights and obligations.

 

Background and history

TRIPS was negotiated at the end of the Uruguay Round of the General Agreement on Tariffs and Trade (GATT) in 1994. Its inclusion was the culmination of a program of intenselobbying by the United States, supported by the European Union, Japan and other developed nations. Campaigns of unilateral economic encouragement under the Generalized System of Preferences and coercion under Section 301 of the Trade Act played an important role in defeating competing policy positions that were favored by developing countries, most notably Korea and Brazil, but also including Thailand, India and Caribbean Basin states. In turn, the United States strategy of linking trade policy to intellectual property standards can be traced back to the entrepreneurship of senior management at Pfizer in the early 1980s, who mobilized corporations in the United States and made maximizing intellectual property privileges the number one priority of trade policy in the United States (Braithwaite and Drahos, 2000, Chapter 7).

After the Uruguay round, the GATT became the basis for the establishment of the World Trade Organization. Because ratification of TRIPS is a compulsory requirement of World Trade Organization membership, any country seeking to obtain easy access to the numerous international markets opened by the World Trade Organization must enact the strict intellectual property laws mandated by TRIPS. For this reason, TRIPS is the most important multilateral instrument for the globalization of intellectual property laws. States like Russia and China [3] that were very unlikely to join the Berne Convention have found the prospect of WTO membership a powerful enticement.

Furthermore, unlike other agreements on intellectual property, TRIPS has a powerful enforcement mechanism. States can be disciplined through the WTO’s dispute settlementmechanism.

The requirements of TRIPS

TRIPS requires member states to provide strong protection for intellectual property rights. For example, under TRIPS:

  • Copyright terms must extend at least 20 years, unless based on the life of the author. (Art. 12 and 14)[4][not in citation given]
  • Copyright must be granted automatically, and not based upon any “formality,” such as registrations, as specified in the Berne Convention. (Art. 9)
  • Computer programs must be regarded as “literary works” under copyright law and receive the same terms of protection.
  • National exceptions to copyright (such as “fair use” in the United States) are constrained by the Berne three-step test
  • Patents must be granted for “inventions” in all “fields of technology” provided they meet all other patentability requirements (although exceptions for certain public interests are allowed (Art. 27.2 and 27.3)[5] and must be enforceable for at least 20 years (Art 33).
  • Exceptions to exclusive rights must be limited, provided that a normal exploitation of the work (Art. 13) and normal exploitation of the patent (Art 30) is not in conflict.
  • No unreasonable prejudice to the legitimate interests of the right holders of computer programs and patents is allowed.
  • Legitimate interests of third parties have to be taken into account by patent rights (Art 30).
  • In each state, intellectual property laws may not offer any benefits to local citizens which are not available to citizens of other TRIPS signatories under the principle of national treatment (with certain limited exceptions, Art. 3 and 5).[6] TRIPS also has a most favored nation clause.

Many of the TRIPS provisions on copyright were copied from the Berne Convention for the Protection of Literary and Artistic Works and many of its trademark and patent provisions were modeled on the Paris Convention for the Protection of Industrial Property.

Access to essential medicines[

The most visible conflict has been over AIDS drugs in Africa. Despite the role that patents have played in maintaining higher drug costs for public health programs across Africa, this controversy has not led to a revision of TRIPs. Instead, an interpretive statement, the Doha Declaration, was issued in November 2001, which indicated that TRIPs should not prevent states from dealing with public health crises. After Doha, PhRMA, the United States and to a lesser extent other developed nations began working to minimize the effect of the declaration.[7]

A 2003 agreement loosened the domestic market requirement, and allows developing countries to export to other countries where there is a national health problem as long as drugs exported are not part of a commercial or industrial policy.[8] Drugs exported under such a regime may be packaged or colored differently in order to prevent them from prejudicing markets in the developed world.

In 2003, the Bush administration also changed its position, concluding that generic treatments might in fact be a component of an effective strategy to combat HIV. Bush created the PEPFAR program, which received $15 billion from 2003–2007, and was reauthorized in 2008 for $48 billion over the next five years. Despite wavering on the issue ofcompulsory licensing, PEPFAR began to distribute generic drugs in 2004-5.

Software and business method patents

Another controversy has been over the TRIPS Article 27 requirements for patentability “in all fields of technology”, and whether or not this necessitates the granting of softwareand business method patents.

Implementation in developing countries

The obligations under TRIPS apply equally to all member states, however developing countries were allowed extra time to implement the applicable changes to their national laws, in two tiers of transition according to their level of development. The transition period for developing countries expired in 2005. The transition period for least developed countries to implement TRIPS was extended to 2013, and until 1 January 2016 for pharmaceutical patents, with the possibility of further extension.[9]

It has therefore been argued that the TRIPS standard of requiring all countries to create strict intellectual property systems will be detrimental to poorer countries’ development.[10] Many argue[who?] that it is, prima facie, in the strategic interest of most if not all underdeveloped nations to use the flexibility available in TRIPS to legislate the weakest IP laws possible.[11]

This has not happened in most cases. A 2005 report by the WHO found that many developing countries have not incorporated TRIPS flexibilities (compulsory licensing, parallel importation, limits on data protection, use of broad research and other exceptions to patentability, etc.) into their legislation to the extent authorized under Doha.[12]

This is likely caused by the lack of legal and technical expertise needed to draft legislation that implements flexibilities, which has often led to developing countries directly copying developed country IP legislation,[13] or relying on technical assistance from the World Intellectual Property Organization (WIPO), which, according to critics such as Cory Doctorow, encourages them to implement stronger intellectual property monopolies.

Banerjee and Nayak[14] shows that TRIPS has a positive effect on R&D expenditure of Indian pharmaceutical firms.

Post-TRIPS expansion

Unbalanced scales.svg
 The neutrality of this article is disputed. Relevant discussion may be found on the talk page. Please do not remove this message until the dispute is resolved. (May 2011)

In addition to the baseline intellectual property standards created by the TRIPS agreement, many nations have engaged in bilateral agreements to adopt a higher standard of protection. These collection of standards, known as TRIPS+ or TRIPS-Plus, can take many forms.[15] General objectives of these agreements include:

Panel reports

According to WTO 10th Anniversary, Highlights of the first decade, Annual Report 2005 page 142,[16] in the first ten years, 25 complaints have been lodged leading to the panel reports and appellate body reports on TRIPS listed below.

The WTO website has a gateway to all TRIPS disputes (including those that did not lead to panel reports) here [1].

Criticism

Since TRIPS came into force it has received a growing level of criticism from developing countries, academics, and non-governmental organizations. Some of this criticism is against the WTO as a whole, but many advocates of trade liberalization also regard TRIPS as bad policy. TRIPS’s wealth concentration effects (moving money from people in developing countries to copyright and patent owners in developed countries) and its imposition of artificial scarcity on the citizens of countries that would otherwise have had weaker intellectual property laws, are common bases for such criticisms.

Peter Drahos writes that “It was an accepted part of international commercial morality that states would design domestic intellectual property law to suit their own economic circumstances. States made sure that existing international intellectual property agreements gave them plenty of latitude to do so.”[28]

Daniele Archibugi and Andrea Filippetti[29] argue that the importance of TRIPS in the process of generation and diffusion of knowledge and innovation has been overestimated by both their supporters and their detractors. Claude Henry and Joseph E. Stiglitz[30] argue that the current intellectual property global regime may impede both innovation and dissemination, and suggest reforms to foster the global dissemination of innovation and sustainable development.

See also

Related treaties and laws

Related organizations

References

  1. Jump up^ “WTO TRIPS implementation”. International Intellectual Property Alliance. Retrieved22 May 2012.
  2. Jump up^ See TRIPS Art. 1(3).
  3. Jump up^ Farah, Paolo Davide & Cima, Elena (2010) ‘SSRN.com China’s Participation in the World Trade Organization: Trade in Goods, Services, Intellectual Property Rights and Transparency Issues” in Aurelio Lopez-Tarruella Martinez (ed.), El comercio con China. Oportunidades empresariales, incertidumbres jurídicas, Tirant lo Blanch, Valencia (Spain) 2010, pp. 85–121. ISBN 978-84-8456-981-7.
  4. Jump up^ “intellectual property (TRIPS) – agreement text – standards”. WTO. 1994-04-15. Retrieved 2012-04-16.
  5. Jump up^ World Trade Organization, “Part II — Standards concerning the availability, scope and use of Intellectual Property Rights; Sections 5 and 6”, Agreement on Trade-Related Aspects of Intellectual Property Rights
  6. Jump up^ World Trade Organization, “Part I — General Provisions and Basic Principles”,Agreement on Trade-Related Aspects of Intellectual Property Rights
  7. Jump up^ cf. Timmermann, Cristian, and Henk van den Belt. 2013. Intellectual property and global health: from corporate social responsibility to the access to knowledge movement. Liverpool Law Review 34 (1):47-73. also available at http://edepot.wur.nl/252885
  8. Jump up^ World Trade Organization (1 September 2003), Implementation of paragraph 6 of the Doha Declaration on the TRIPS Agreement and public health
  9. Jump up^ World Trade Organisation, IP – http://www.wto.org/english/tratop_e/trips_e/tripfq_e.htm
  10. Jump up^ IP Justice policy paper for the WIPO development agenda, IP Justice
  11. Jump up^ Trade and Health. McGill-Queen’s University Press. 2007. p. 33. |first1= missing|last1= in Authors list (help)
  12. Jump up^ Musungu, Sisule F.; Oh, Cecilia (August 2005), The use of flexibilities in TRIPS by developing countries: can they promote access to medicines?, Commission on Intellectual Property Rights, Innovation and Public Health (CIPIH)
  13. Jump up^ Finger, J. Michael (2000). “The WTO’s special burden on less developed countries”(PDF). Cato Journal 19 (3).
  14. Jump up^ Banerjee and Nayak, Effects of Trade Related Intellectual Property Rights on the R&D Expenditure of Indian Pharmaceutical Industry,2014 ‘Journal of Pharmaceutical Health Services Research.
  15. Jump up^http://www.oxfordscholarship.com/view/10.1093/acprof:oso/9780195390124.001.0001/acprof-9780195390124-chapter-8
  16. Jump up^ World Trade Organization (2005). “Annual Report 2005”.
  17. Jump up^ “2005 News items – Panel reports out on geographical indications disputes”. WTO. 2005-03-15. Retrieved 2012-04-16.
  18. Jump up^ http://www.wto.org/english/tratop_e/dispu_e/1391da.pdf
  19. Jump up^ http://www.wto.org/english/tratop_e/dispu_e/1391db.pdf
  20. Jump up^ http://www.wto.org/english/tratop_e/dispu_e/170abr_e.pdf
  21. Jump up^ http://www.wto.org/english/news_e/news00_e/1234da.pdf
  22. Jump up^ http://www.wto.org/english/news_e/news00_e/1234db.pdf
  23. Jump up^ http://www.worldtradelaw.net/reports/wtopanelsfull/canada-pharmaceuticals(panel)(full).pdf
  24. Jump up^ http://www.wto.org/english/tratop_e/dispu_e/176r_e.pdf
  25. Jump up^ http://www.wto.org/english/tratop_e/dispu_e/176abr_e.pdf
  26. Jump up^ http://www.worldtradelaw.net/reports/wtopanelsfull/india-patents(panel)(ec)(full).pdf
  27. Jump up^ http://www.worldtradelaw.net/reports/wtopanelsfull/indonesia-autos(panel)(full).pdf
  28. Jump up^ Drahos with Braithwaite, Information Feudalism, New Press 2002, p38
  29. Jump up^ Archibugi, D. and Filippetti, A. (2010) ‘The globalization of intellectual property rights: Four learned lessons and four thesis‘, Journal of Global Policy, 1: 137-49.
  30. Jump up^ Henry, C. and Stiglitz, J. (2010) ‘Intellectual Property, Dissemination of Innovation and Sustainable Development‘, Journal of Global Policy, 1: 237-51.

Source

  • Braithwaite and Drahos, Global Business Regulation, Cambridge University Press, 2000
  • Westkamp, ‘TRIPS Principles, Reciprocity and the Creation of Sui-Generis-Type Intellectual Property Rights for New Forms of Technology’ [2003] 6(6) The Journal of World Intellectual Property 827-859, ISSN: 1422-2213
  • Banerjee and Nayak, ‘Effects of trade related intellectual property rights on the research and development expenditure of Indian pharmaceutical industry’ [2014] 5 Journal of Pharmaceutical Health Services Research 89-94.

External links

Share

Overview of the Patent System in Korea

 PATENTS, Uncategorized  Comments Off on Overview of the Patent System in Korea
Jan 212015
 

 South Korea

KIPO logo

http://www.kipo.go.kr/kpo/user.tdf?a=user.english.main.BoardApp&c=1001

 

The Korean Intellectual Property Office (KIPO) is the patent office and intellectual property office of South Korea. In 2000, the name of the office was changed from “Korean Industrial Property Office” to “Korean Intellectual Property Office”.[1] It is located in Daejeon Metropolitan City.[2]

References

  1.  KIPO web site, KIPO’s history. Consulted on January 20, 2008.
  2.  KIPO web site, Contact Us. Consulted on January 20, 2008.

External links

 

 

Overview of the Patent System in Korea

KIPRIS - Korea Intellectual Property Rights Information Service
Korean Intellectual Property Office

http://www.kipris.or.kr/enghome/main.jsp

Patent

Patent Search Websites; IP Related Organizations in Korea …

http://engpat.kipris.or.kr/engpat/searchLogina.do?next=MainSearch

Searching in databases – Korea

Tips & tricks for searching in databases

Easy, step-by-step instructions on how to use official Korean databases. Click on the links below to download the respective search guides.

Number search and document retrieval

English machine translations

Legal status information

Searching trade marks and designs

Searching information on pharmaceutical patents

Share

Saudi Patent Office AND GULF ( GCC Patent office)

 PATENTS, Uncategorized  Comments Off on Saudi Patent Office AND GULF ( GCC Patent office)
Jan 212015
 

http://www.gccpo.org/DefaultEn.aspx

The Patent Office of the Cooperation Council for the Arab States of the Gulf is delighted to announce launching the electronic filing system for patent applications “Protection” in its trial version, starting from the second of August of 2014, through the office’s official website on the internet www.gccpo.org.
The “Protection” system launch comes within the frame of the office’s comprehensi…More

 

The GCC Patent Office (GCCPO) is a regional patent office based in Riyadh, Saudi Arabia, within the Secretariat General of the Gulf Cooperation Council (GCC). It was established in 1992 and began operations in 1998. The GCC Patent Office grants patents valid in all GCC member states. The first GCC patent was granted in 2002. As of 2013, it employed about 30 patent examiners.[1]

References

Mizael Al-Harbi, Hussam Al-Muqhim (18 April 2013). “Gulf countries: introduction to the GCC patent system”. East meets West 2013. Austria.

External links

 

The Gulf Cooperation Council Patent Office (GCC Patent Office) is a unified patent office that serves as a convention patent office for the states of the Gulf namely, Saudi Arabia, Bahrain, Kuwait, Oman, Qatar and United Arab Emirates. The GCC Patent Office became operational in 1998. Saudi Arabia is a member of the Gulf Cooperation Council. A patent issued by the GCC Patent Office is valid and enforceable in all GCC States.

Under GCC Patent Law, it is possible to claim priority from an earlier foreign application. As compared with the Saudi Patent Office the examination process is much faster in the GCC Patent Office. Moreover, the GCC Patent Office has the following advantages:

  1. Filing a GCC Patent application will be more cost-effective than filing six separate national applications.. Therefore, by filing one application at the GCC Patent Office, protection is granted in all GCC States at a reduced cost.
  2. A Patent granted by the GCC Patent Office is valid and enforceable in all GCC States (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and U.A.E)
  3. The term of protection under GCC Patent Law is 20 years counted from the date of filing the patent application with the GCC Patent Office as opposed to 15 years as far as the other national patent laws are concerned.
  4. Duplication of registration is possible. It is possible to file a patent application in one or more of the GCC States and at the same time seek convention protection by filing at the GCC Patent Office.
  5. Compulsory Licensing under GCC Patent Law is now subjected to detailed conditions in conformity with the provision of the Trips Agreement.
  6. Importation of a patented product into GCC States will be considered as full exploitation of the invention.
  7. The GCC is taking the necessary steps to join Paris and PCT treaties in the near future.
  8. The Examination of applications is carried out by an Austrian and Australian Patent Offices.

The requirements for filing a new GCC patent application are as follows:

  1. Documents that must be filed along with the application:
    Specifications, Claims, Drawings (if any) and Abstract of the invention in English and Arabic.
  2. Documents that may be filed belatedly within 90 days from the filing date:
    1. A Power of Attorney from the applicant.
    2. An Extract from the Commercial Register or a certified copy of the Certificate of Incorporation of the applicant if the applicant is a corporate body.
    3. A Deed of Assignment, if the applicant is not the inventor.
    4. A Certified copy of the Priority document, if the applicant is claiming priority on the basis of a foreign application. Item Nos. 1,2 & 3 should be legalized up to any one of the GCC States Consulates.

Image result for saudi arabia

Industrial property is one of the branches of intellectual property. It refers to the protection of rights related to the creations of the mind applied in industrial, commercial, and agricultural fields. It covers:

• Inventions
• Industrial Designs
• Plant Varieties
• Layout Designs of integrated circuits
• Trademarks
• Geographical indications of source

King Abdulaziz City for Science and Technology (KACST) grants protection documents for inventions, layout designs of integrated circuits, plant varieties and industrial designs.

History of Industrial Property in Saudi Arabia.

In 1982, KACST was notified of the Royal Decree approving the accession of Saudi Arabia to the World Intellectual Property Organization (WIPO). Accordingly, patents has been assigned to KACST since intellectual property is essentially about patents and technology transfer and KACST is the scientific body qualified for this mission.

The first Law of Patents was issued by the Royal Decree No. (M / 38) dated 10/6/1409 H (18/1/1989 AD). The Law aimed to provide protection for inventions in Saudi Arabia, and it was modified in 19 / 7 / 1425 H (4/9/2004 AD).

The modified Law of Patents, Layout Designs of Integrated Circuits, Plant Varieties, and Industrial Designs was issued by the Royal Decree No. (M/27) dated 17/7/2004 and was published in the Official Gazette (Om Alqura) in 7/8/2004, and became effective as of 5/9/2004.

Kingdom of Saudi Arabia

المملكة العربية السعودية
Al-Mamlakah al-Arabiyah as-Sa’ūdiyah

King Abdullah of Saudi Arabia (left) and Salman bin Abdulaziz Al Saud, the Crown Prince of Saudi Arabia on the right.

Patent Application Flowchart

 

Desgin Application Flowchart

Saudi Arabia has ratified the Berne Convention for the Protection of Literary and Artistic Works of 1886, revised in Paris on 24th July 1971 and the Paris Convention for the Protection of Industrial Property of 1883, both with effect from 11th March 2004. Three government authorities have authority to protect and enforce intellectual property rights: the Ministry of Commerce and Industry for trademarks, the Ministry of Culture and Information for copyright, and King Abdulaziz City for Science and Technology for patents.

Trademarks:
Trademarks are governed by the Trademarks Regulation, Royal Decree No. M/21 of 28th Jumada Awal 1423 Hejra corresponding to 8th August 2002 Gregorian, and its Implementing Rules of the same year. Applications for registration must be made to the Trademarks Office of the Ministry of Commerce and Industry which applies the ‘Nice Classification’ in accordance with the Agreement Concerning the International Classification of Goods and Services for the Purposes of the Registration of Marks of 1957.

Deera Square, central Riyadh. Known locally as “Chop-chop square”, it is the location of public beheadings.[142]

Applications must contain the following particulars:
01. A copy of the trademark required to be registered.
02. Name, title, address, nationality and trade name of the applicant (if any). If the applicant is a juristic person, the name, address of the head office and nationality must be stated.
03. Where the application is submitted by an attorney, his name, title and address must be stated.
04. Description of the trademark required to be registered.
05. The products or services in respect of which the trademark is required to be registered, and the classification thereof.
06. Signature of the applicant or the attorney thereof.
07. Ten representations of the trademark identical to the trademark sample shown in the application for registration.
08. A copy of the power of attorney together with the original for verifying purposes must be attached where the application was submitted by an attorney of the person concerned.
09. Evidence of payment of application fees as stipulated in the Trademarks Regulation.

It is not permitted to register in Saudi Arabia, by other than its rightful owner, a trademark that is similar to an internationally known mark. Registration of a trademark allows holders protection for ten years from the date of application, renewable for similar periods. Any renewal must be specifically applied for before the end of the last year of expiry of the registration, and the procedure for renewal is the same as the one for the initial registration of the trademark. Service marks are included in the definition of trademarks. A trademark is deemed owned by the person who effects the registration. Once the registration is effected in the trademarks register, the party who has registered the trademark shall be considered the owner thereof to the exclusion of others.

A trademark can be licensed, pledged or transferred by the rightful owner. The trademark may be deleted or cancelled if it is not used for five consecutive years. Penalties for infringement of a valid trademark include imprisonment for a period of not more than one year and a fine of not less than SR50,000 and not more than SR1,000,000. Any civil or criminal disputes arising from the infringement are settled by the Board of Grievances.

The Nejd landscape: desert and the Tuwaiq Escarpment near Riyadh

Patents:
There are at present two overlapping patents systems in Saudi Arabia. The GCC Patents of Inventions Regulation of 2001, which is an amendment of an earlier statute of 1992, was approved in Saudi Arabia by Royal Decree No. M/28 of 2001. This permits the registration of patents with effect throughout the GCC countries. The GCC Patent Office is based in Riyadh.

Under Saudi Arabian law, patents are governed by the Layout Designs of Integrated Circuits, Plant Varieties, and Industrial Models Regulation, Royal Decree No. M/27 of 20th Jumada Awal 1425 Hejra corresponding to 17th July 2005 Gregorian, which gives effect to the Paris Convention for the Protection of Industrial Property under Saudi Arabian domestic law.

A protection document is granted by the General Directorate of Patents at King Abdulaziz City for Science and Technology, which gives full protection within the Kingdom to an invention, a layout design of an integrated circuit, a plant variety, or an industrial design. The protection document grants the owner the right to commercially exploit the subject matter of protection.

Applications for a protection document must be filed at the Directorate in the Arabic language, and must include:
01. Names and addresses of the applicant(s) and inventor(s);
02. Name and address of the local agent and the authorization, if the applicant resides outside the Kingdom;
03. A brief title of the subject matter of the application, an original copy and certified copies of the complete specification and certified copies of other relevant details thereof like examination and research reports;
04. Priority and disclosure information including previous filings; and
05. Evidence of payment of the filing fee at a designated bank, stipulated by the Directorate.
The protection document is the personal right of the owner and he may transfer or assign it or grant a contractual licence to others to commercially exploit the subject matter of protection. Protection is granted to the owner for a duration of 20 years for an invention, 10 years for an industrial design and a layout design of an integrated circuit, and 20 to 25 years for a new plant variety. The above periods are renewable, for an annual fee.

Provinces of Saudi Arabia

Copyright
The Copyright Regulation, Royal Decree No. M/41 of 2nd Rajab 1424 Hejra corresponding to 30th August 2003 Gregorian and its Implementing Rules, Resolution of the Minister of Commerce and Industry No. M/W/1788/1 of 10th Rabi Thani 1425 Hejra corresponding to 30th May 2004 Gregorian, define copyright protection to include architectural designs, speeches, theatrical, musical, photographic and cinematographic works, as well as works for radio and television, maps, video tapes and computer software. Copyright protection is not subject to any registration or renewal. The Regulation gives the author financial and moral rights, to print or publish the work, to make amendments or to delete his work, to withdraw it from circulation, and to assign it as he wishes.

In general the duration of protection afforded to different types of Copyright works is as follows:
01. The period of protection of copyright for the author of a work shall be for the duration of his life and for a period of fifty years following his death.
02. The period of protection for works where the author is a corporate entity, or if the author’s name is unknown, shall be fifty years from the date of the first publication of the work.
03. The protection period for sound works, audio-visual works, films, collective works and computer programs is fifty years from the date of the first show or publication of the work, regardless of republication.
04. The protection period for applied art (handcrafted or manufactured) and photographs shall be twenty-five years from the date of publication.
05. The protection period for broadcasting organizations shall be twenty years from the date of the first transmission of program or broadcast materials.

Office of Saudi Aramco, world’s most valuable company and main source of revenue for the state.

A special Copyright Violations Committee under the authority of the Ministry of Culture and Information presides over copyright infringement issues and it has broad powers to punish the infringer of a valid copyright including a fine of up to SR250,000 in the case of first time offenders, and this can be raised to SR500,000 if there is repeated infringement. The Committee may issue injunctions in certain cases and also order imprisonment of an offender. Any decision of the Violations Committee can be appealed by filing a claim with the Board of Grievances.

 

kacst

Saudi Arabia is the largest and richest of the Gulf States. Its wealth derives mainly from its vast reserves of oil and natural gas, which places the country as the largest exporter of petroleum and give it a leading role in the Organization of the Petroleum Exporting Countries. It possesses about one-fifth of the world’s proven petroleum reserves. The Intellectual Property framework of Saudi Arabia has evolved to protect the different intellectual properly rights and to cope with the rapid globalization and technological change. Both globalization and technological advancement have presented significant economic opportunities and challenges to the IP system. As a result, IP rights have become increasingly important in the country, but many of the challenges facing the IP system have yet to be addressed.

The Patent Office in Saudi Arabia is located at the King Abdulaziz City for Science & Technology, an independent scientific organization of the Saudi Arabian Government established back in the year 1977. The Patent Office’s main activities and objectives are to:
(1) Apply the patent law and its implementing regulations: Law of Patents, Layout Designs of Integrated Circuits, Plant Varieties and Industrial Designs
(2) Grant Saudi patents, Layout Designs of Integrated Circuits, Plant Varieties and Industrial Designs
(3) Establish a Registry for the collection of local and foreign Layout Designs of Integrated Circuits, Plant Varieties and Industrial Designs
(4) Publish the Patents Gazette
(5) Encourage the inventiveness of Saudi nationals.
The Office has taken a number of measures during the past years to hire and train examiners and translators in order to adequately handle patent applications.

Legislation
Law no. 159 on the Protection of Patents, Layout Designs of Integrated Circuits, Plant Varieties and Industrial Models.

Types of Patents
– Patents of Invention
– Divisional Patents

Priority Claim
Saudi Arabia is a member of the Paris Convention. Applicants can benefit from a right of priority of 12 months to file a corresponding Saudi patent application.

Patent Cooperation Treaty
Saudi Arabia has joined the PCT but still the entry of national phase of PCT application is not possible as the relevant regulations and laws have not been issued, we expect the implementation of PCT within next 6-12 months.

The Mosque of the Prophet in Medina containing the tomb of Muhammad.

Definition of an Invention
An invention must be novel, involves an inventive step and capable of industrial application. The invention may be a product, an industrial process or relates to either (Article 43).

Types of Claims
Product and process claims are acceptable. When a patent is granted for a process, any product made directly by such a process is also protected (Article 47(b)).

Exception to Protection
An invention is not patentable if it is: a discovery; a scientific theory or mathematical method; an aesthetic creation such as a literary, dramatic, or artistic work; a scheme or method for performing a mental act, games or business methods; the presentation of information; or a computer program.

Examination
– Novelty: the invention must never have been made public in any way, anywhere in the world, before the filing date or the priority date.
– Inventiveness: an invention involves an inventive step if, when compared with what is already known, it would not be obvious to someone skilled in the relevant field.
– Industrial applicability: an invention must be capable of being made or used in some kind of industry.

Laboratory buildings at KAUST

Novelty
Absolute novelty is required. Any act that makes an invention available to the public before the filing date or priority date has the effect of barring the invention from being patented in Saudi Arabia (Absolute Novelty). Examples of acts that can make an invention available to the public are publications, sales, public oral disclosures and public demonstrations or use, etc. However, the patent application can still be filed if disclosure was very limited and can not be cited by the examiner. Also, a one year grace period is available if the disclosure of the invention was proven to be made without the knowledge or consent of the inventor (Article 44).  Wrong statement article 44 if disclosed within the priority period, but the exception is under article 30 of Implementing Regulations where the grace period is 6 months if the disclosure occurred because of abusive action.

Application Workflow
A formal examination is conducted first. If application fails to meet all the set requirements, the applicant will be notified and will be given a period of 90 days to complete the application. Once completed, the application will proceed to substantive examination. The examiner will assess the application for patentability (novelty and industrial applicability). If the claimed invention is not patentable, the applicant will be requested to present counter-arguments within 90 days from notification date. If the claimed invention is patentable, the applicant will be requested to settle the grant and publication fees. Accordingly, the letters patent will be issued and the decisions to grant the patent will be published in the Patent Official Gazette for opposition purposes.

Opposition
Oppositions may be filed within 90 days from publication date before the Board of Grievances.

Protection Term
The term of protection is 20 years from filing date.

Annuities
A maintenance fee is due annually on patents and is payable the first 3 months of each calendar year following the year the patent application was filed. There is a 3-month grace period for late payment with a surcharge.

Compulsory Licensing
A patent has to be worked. If the patent is not being fully exploited by the patentee within 4 years from the date of filing or 3 years from the date of grant, the patent will be subject to compulsory licensing under the provisions of the law.
Naming of the Inventor on the Letters Patent
Compulsory

Ibn Saud, the first king of Saudi Arabia

Employer and Employee’s Rights
Employer’s Rights
The employer shall be the patentee
(1) if the invention is made in execution of a contract or a commitment for the execution of inventive efforts, unless the work contract stipulates otherwise, or
(2) if the employee would not have developed the subject matter of the protection had he not used facilities, means or data made available through his employment
Employee’s Rights
The employee has the right to receive a remuneration to be agreed upon with the consent of both parties or assessed in light of the various circumstances of the contract of employment and the economic importance of the subject matter of the protection. Any special agreement depriving the employee of this right shall be null and void.
General Provisions
A patent application filed by the employee within two years from the date of termination of employment will be considered as if submitted during employment.
All previous provisions will apply to government employees.

Patent Linkage
Requests for marketing approval of generic drugs must include details on the corresponding patent if available (filing no., filing date, and country of grant). The SFDA will then contact the Saudi Patent Office to confirm whether a patent is involved before giving marketing approval. The GCC Patent Office is not usually contacted.

Filing Requirements
1. Power of attorney, legalized up to the Saudi Consulate
2. 2 copies of the specifications in English with Arabic translation
3. 2 sets of drawings in Arabic and one in English.
4. Deed of assignment from the inventor(s), legalized up to the Saudi Consulate
5. Copy of priority document, if priority is claimed, certified.
Item 3 must be submitted at the time of filing. Document 5 must be submitted within 12 months from priority date.
Documents 1 and 4 may be submitted within 1 month from filing date.

Verses from the Quran. The Quran is the official constitution of the country and a primary source of law. Saudi Arabia is unique in enshrining a religious text as a political document[130]

GCC Protection
Patent protection in Saudi Arabia can also be obtained through the Gulf Cooperation Council unified patent registration system (GCC patent law of 1999).

2011 Figures
Saudi Arabia ranked first among the Arab countries in the number of patents granted for the year 2011 which amounted to 147, based on WIPO sources. It also ranked first in the number of patents filed in the same year which amounted to 78.

FAQ – Saudi Arabia (SA)

 

For more specific legal questions relating to the Saudi Arabian patent system, please contact International_legal_affairs@epo.org.

Questions

General information about IP in Saudi Arabia

From filing to grant

After grant

Sources of information

Supplicating pilgrim at Masjid Al Haram, Mecca

Answers

General information about IP in Saudi Arabia

How to protect an invention in Saudi Arabia

There are two options for protecting an invention on Saudi Arabian territory:

  1. The first option is to file a patent application with the Saudi Arabian Patent Office. If a patent is granted, the invention will be protected only in Saudi Arabia.
  2. The second option is to file a patent application with the Gulf Cooperation Council (GCC) Patent Office. The GCC is a regional organisation comprising six Arab countries: the Kingdom of Saudi Arabia, Qatar, Kuwait, the United Arab Emirates, the Sultanate of Oman, and Bahrain. The GCC Patent Office is a regional office that registers patents in the member states of the GCC. Patents granted by the GCC Patent Office are valid in all GCC member states.

GCC Patent Office website

All the information presented below relates to the first option, protection via the Saudi Arabian Patent Office.

 

What types of industrial property rights exist in Saudi Arabia?

Saudi Arabia has patents, plant varieties, industrial designs, layout designs of integrated circuits and trade marks, but not utility models. Patents and designs can be registered at the Saudi Arabian Patent Office (official name: General Directorate of Patents at King Abdulaziz City of Science and Technology (KACST)). Trade marks can be registered at the Ministry of Commerce and Industry.

 

How long are the terms of protection of Saudi Arabian intellectual property rights?

The terms of protection for the different types of intellectual property are as follows:

  • patents: 20 years from the date of filing
  • plant varieties: 20 years
  • industrial designs: 10 years
  • layout designs of integrated circuits: 10 years

riyadh

When may a patent not be granted?

Article 4 of the Saudi Arabian Patent Law states the following:

“(a) The protection document shall not be granted if its commercial exploitation violates the Shari’ah (Islamic law).

(b) The protection document shall not be granted if its commercial exploitation is harmful to life, to human, animal or plant health, or is substantially harmful to the environment.”

Riyadh
Riyadh

What inventions cannot be patented in Saudi Arabia?

Article 45 of the Saudi Arabian Patent Law states the following:

“In the application of provisions of this Law, the following shall not be regarded as inventions:

(a) Discoveries, scientific theories and mathematical methods.

(b) Schemes, rules and methods of conducting commercial activities, exercising pure mental activities or playing a game.

(c) Plants, animals and processes – which are mostly biological – used for the production of plants or animals, with the exception of micro-organisms, non-biological and microbiology processes.

(d) Methods of surgical or therapeutic treatment of human or animal body and methods of diagnosis applied to human or animal bodies, with the exception of products used in any of these methods.”

The exclusion also applies to computer programs and any other copyright work.

Laws & Regulations

Jeddah
Jeddah

Can computer software be patented in Saudi Arabia?

Computer programs as such are not patentable, but may be protected by copyright. Computer-related inventions may be patentable in Saudi Arabia if the requirements for patentability are met.

Laws & Regulations

 

Is Saudi Arabia a member of the Patent Cooperation Treaty (PCT)?

As of 3 August 2013, Saudi Arabia will be bound by the PCT. From that date onwards, nationals and residents of Saudi Arabia will be entitled to file international applications under the PCT.

 

From filing to grant

As a foreign applicant, do I need to appoint a professional representative in Saudi Arabia?

All non-residents wishing to apply for a patent require an authorised Saudi Arabian representative. Applicants have to file a power of attorney which has been duly notarised and legalised by the consulate of Saudi Arabia.

More information:

Professional representative

 

What language must I use for a patent application in Saudi Arabia?

Documents submitted under the Saudi Arabian Law of Patents must be in Arabic.

Can I claim priority for an application filed in Saudi Arabia?

Yes, the priority term is 12 months from the earliest claimed priority, as stipulated in the Paris Convention. Saudi Arabia has been a member of the Paris Convention since 2004.

 

What do I need to do to get an early filing date in Saudi Arabia?

Does Saudi Arabia allow divisional applications?

Yes. Where an application contains two or more inventions, applicants may submit a divisional application on their own initiative any time before the decision to grant or reject the application.

 

Do I have to file a request for examination (“deferred examination”) in Saudi Arabia?

You do not need to file a request for examination. Applications are examined automatically, on the basis of the filing date. It is possible to withdraw applications.

 

Can I withdraw my application before it is published in Saudi Arabia?

Yes, you can withdraw an application before it is published.

 

Can I request that my application in Saudi Arabia be published earlier than 18 months from the filing (or earliest priority) date?

No, it is not possible to request early publication of an application.

 

Can I submit third-party observations on a Saudi Arabian patent application?

No, it is not possible to submit third-party observations.

King Abdullah Economic City

What is the time limit for responding to official actions in Saudi Arabia?

Responses to official actions should be submitted within 90 days from the date of the action.

 

After grant

When do I have to pay annual fees in Saudi Arabia?

Annual fees are due at the beginning of each year (1 January until 30 March), starting from the year following the filing date.

 

Is there a grace period for paying annual fees in Saudi Arabia?

Applicants or patent holders who fail to pay within a maximum period of three months from the due date are liable to pay double the amount of the fee. If they fail to pay after being warned during the three months following the expiration of the first three months, the patent will cease to be valid and this will be recorded in the Register and published in the Gazette.

 

Can a lapsed patent be restored in Saudi Arabia?

In case of force majeure it is possible to have a lapsed patent restored at the Saudi Arabian Patent Office.

 

Makkah in Saudi Arabia

Can I request an extension of the patent term in Saudi Arabia?

No. In Saudi Arabia the 20-year term for patents cannot be extended. The Saudi Arabian Patent Law does not include any provisions on patent term extensions or supplementary protection certificates (SPCs).

 

How can I challenge a granted patent in Saudi Arabia?

Within 90 days from publication of the decision to grant, any interested party may apply for partial or total revocation of the patent.

Invalidation is possible for a third party at any time after grant and must be raised before a separate governmental body (Appeals Committee).

 

Sources of information

Where can I search Saudi Arabian patent information in English?

The Saudi Arabian Patent Office has an English-language database known as “IP search”. On this platform you can perform searches according to dates, numbers or applicant/inventor names.

IP Search

If you require a more detailed answer, please send us your question using the contact form.

Where can I find English abstracts of Saudi Arabian patent documents?

In general, the Saudi Arabian Patent Office does not produce any English abstracts for its patent documents. Where a non-Saudi Arabian applicant files an application, the abstract may also be in English (and in Arabic), while the rest of the patent has to be in Arabic only. Therefore, English abstracts are also available in certain circumstances.

 

Where can I get an English machine translation of a Saudi Arabian patent?

There are no machine translations of Saudi Arabian patents available yet.

 

Where can I find legal-status information on Saudi Arabian patents in English?

In general, legal-status information for Saudi Arabian patents is not yet available, but a brief “application status” can be found together with the bibliographic information in the “IP search” database.

 

Where can I find official information about fees in Saudi Arabia?

Information about fees is currently available in Arabic only.

Schedule of fees

 

Where can I find information about patent agents in Saudi Arabia?

The KACST website gives detailed information about the role of patent attorneys and the services they provide. It is available in Arabic only.

Professional representative

If you require a more detailed answer, please send us your question using the contact form.

Share

Methohexital

 Uncategorized  Comments Off on Methohexital
Jan 182015
 

Skeletal formula

 

Ball-and-stick model

Methohexital or methohexitone, (marketed under the brand name Brevital) is a drug which is a barbiturate derivative. It is classified as short-acting, and has a rapid onset of action. It is similar in its effects to sodium thiopental, a drug with which it competed in the market for anaesthetics.

 

Pharmacology

Methohexital binds to a distinct site which is associated with Cl− ionophores at GABAA receptors.[1] This increases the length of time which the Cl− ionopores are open, thus causing an inhibitory effect.

Metabolism of methohexital is primarily hepatic (i.e., taking place in the liver) via demethylation and oxidation.Side-chain oxidation is the primary means of metabolism involved in the termination of the drug’s biological activity.

Protein binding is approximately 73% for methohexital.

Indications

Methohexital is primarily used to induce anesthesia, and is generally provided as a sodium salt (i.e. methohexital sodium). It is only used in hospital or similar settings, under strict supervision.[citation needed] It has been commonly used to induce deep sedation or general anesthesia for surgery and dental procedures. Unlike many other barbiturates, Methohexital actually lowers the seizure threshold, a property that make it particularly useful when anesthesia is provided for a electroconvulsive therapy (ECT). And rapid recovery rate with consciousness being gained within three to seven minutes after induction and full recovery within 30 minuntes is a major advantage over other ECT barbiturates (Schulgasser and Borowitz 1963).

Synthesis

Methohexital, 5-allyl-1-methyl-5-(1-methyl-2-pentinyl barbituric acid, is synthesized in the classic manner of making barbituric acid derivatives, in particular by the reaction of malonic ester derivatives with derivatives of urea.

Methohexital synthesis: W.J. Doran, U.S. Patent 2,872,448 (1959).

The resulting allyl-(1-methyl-2-pentynyl) malonic ester is synthesized by subsequent alkylation of the malonic ester itself, beginning with 2-bromo-3-hexyne, which gives (1-methyl-2-pentynyl)malonic ester, and then by allylbromide. In the final step, reaction of the disubstituted malonic ester with N-methylurea gives desired methohexital.

Methohexital
Skeletal formula
Ball-and-stick model
Systematic (IUPAC) name
5-hex-3-yn-2-yl-1- methyl-5-prop-2-enyl-1, 3-diazinane-2,4,6-trione
Clinical data
AHFS/Drugs.com Consumer Drug Information
Legal status
Routes Intravenous, rectal
Pharmacokinetic data
Bioavailability I.V. ~100%
Rectal ~17%
Metabolism Hepatic
Half-life 5.6 ± 2.7 minutes
Excretion ?
Identifiers
CAS number 151-83-7 Yes
ATC code N01AF01 N05CA15
PubChem CID 9034
DrugBank DB00474
ChemSpider 8683 Yes
UNII E5B8ND5IPE Yes
KEGG D04985 Yes
ChEBI CHEBI:102216 Yes
ChEMBL CHEMBL7413 Yes
Chemical data
Formula C14H18N2O3 
Molecular mass 262.304

 

References

  1. Katzung, Bertram G., Basic and Clinical Pharmacology, 10th ed., p. 406-407

[1]

External links

 

Share

Tipifarnib

 Uncategorized  Comments Off on Tipifarnib
Jan 082015
 

 

Tipifarnib

 

Tipifarnib.png

6-[(R)-Amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone;

(R)-(+)-R 115777; Zarnestra; 192185-68-5

zarnestra, 192185-72-1, R115777, R-115777, IND 58359, UNII-MAT637500A

192185-72-1, 192185-68-5

Molecular Formula: C27H22Cl2N4O
Molecular Weight: 489.39578 g/mol
cas
192185-72-1, 192185-68-5 (racemate), 192185-70-9 (racemic; diHCl), 192185-69-6 (racemic; fumarate)
R115777 is a substance that is being studied in the treatment of acute myeloid leukemia (AML) and other types of cancer. It belongs to the family of drugs called farnesyltransferase inhibitors. It is also called tipifarnib and Zarnestra.

Tipifarnib (trade name Zarnestra) is a farnesyltransferase inhibitor that is being investigated in patients 65 years of age and older with newly diagnosed acute myeloid leukemia (AML). It inhibits the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive. It inhibits prenylation of the CxxX tail motif, which allows Ras to bind to the membrane where it is active. Without this step the protein cannot function.

It is also being tested in clinical trials in patients in certain stages of breast cancer.[1]

For treatment of progressive plexiform neurofibromas associated with Neurofibromatosis type I, it successfully passed phase one clinical trials but was suspended (NCT00029354) in phase two.[2][3] The compound was discovered by and is under investigation byJohnson & Johnson Pharmaceutical Research & Development, L.L.C, with registration number R115777.

Approval process

Tipifarnib was submitted to the FDA by Johnson & Johnson for the treatment of AML in patients aged 65 and over with a New Drug Application (NDA) to the Food and Drug Administration (FDA) on January 24, 2005.

In June 2005, the FDA issued a “not approvable” letter for tipifarnib.[4]

Farnesyltransferase inhibitors block the main post-translational modification of the Ras protein, thus interfering with its localization to the inner surface of the plasma membrane and subsequent activation of the downstream effectors. Although initially developed as a strategy to target Ras in cancer, farnesyltransferase inhibitors have subsequently been acknowledged as acting by additional and more complex mechanisms that may extend beyond Ras involving GTP-binding proteins, kinases, centromere-binding proteins and probably other farnesylated proteins.

A particular farnesyltransferase inhibitor is described in WO 97/21701, namely (R)-(+)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone. The absolute stereochemical configuration of the compound was not determined in the experiments described in the above-mentioned patent specification, but the compound was identified by the prefix “(B)” to indicate that it was the second compound isolated from column chromatography. The compound thus obtained has been found to have the (R)-(+)-configuration. This compound will be referred to below by its published code number R115777 and has the following formula (V).

 

Figure US07572916-20090811-C00002

 

R115777 (Tipifarnib) is a potent, orally active inhibitor of farnesylprotein transferase. It is one of the most advanced of the farnesylprotein transferase inhibitors currently reported to be in clinical development, being one of the agents that have progressed to phase III studies.

R115777 has been found to have very potent activity against neoplastic diseases. Antineoplastic activity in solid tumors, such as breast cancer, as well as in haematological malignancies, such as leukemia, have been observed. Also combination studies have been carried out demonstrating that R115777 can be safely combined with several highly active anticancer drugs.

In WO 01/53289, the racemates (±) (4-(3-chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-(4-methoxy-benzylamino)-(3-methyl-3H-imidazol-4-yl)-methyl]-1-cyclopropylmethyl-1H-quinolin-2-one (racemate 1) and (±) 4-(3-chloro-phenyl)-6-[(6-chloro-pyridin-3-yl)-[(4-methoxy-benzylidene)-amino]-(3-methyl-3H-imidazol-4-yl)-methyl]-1-cyclopropylmethyl-1H-quinolin-2-one (racemate 2) are prepared.

 

Figure US07572916-20090811-C00003

 

After chiral molecule separation using column chromatography, either the benzylamino or the benzilidine moiety of the resulting (+) and/or (−) enantiomers are converted to an amino group under acidic conditions.

In WO 97/21701, it is described (on page 9, line 7-14) that intermediates of formula (XIII), can be prepared by reacting an intermediate of formula (XIV), wherein W is an appropriate leaving group, such as, for example, halo, with an intermediate ketone of formula (XV). In WO 97/21701, it is described that this reaction can be performed by converting the intermediate of formula (XV) into an organometallic compound, by stirring it with a strong base such as butyl lithium and subsequently adding the intermediate ketone of formula (XV). It is further indicated that although this reaction gives at first instance a hydroxy derivative (i.e. R8 is hydroxy), said hydroxy derivative can be converted into other intermediates wherein R8 has another definition by performing art-known (functional group) transformations. The drawings of the compounds of formula (XIII), (XV) and (XIV) have been taken over from WO 97/21701 and the substituents in these drawings are as defined in WO 97/21701.

 

Figure US07572916-20090811-C00004

 

In WO 97/21701, it is also described (from page 7 line 32, to page 8 line 6) that the compounds of formula (XVI), wherein R is C1-6alkyl, R(2-8, 16-19) can be a substituent chosen from lists as defined in WO 97/21701 and R1 has a meaning as defined in WO 97/21701 apart from hydrogen, may be prepared by hydrolysing an intermediate ether of formula (XIII), according to art-known methods, such as stirring the intermediate of formula (XIII) in an aqueous acid solution. An appropriate acid can be for instance hydrochloric acid. Subsequently the resulting quinolinone, wherein R1 is hydrogen, may be transformed into a quinolinone of formula (XVI) by art-known N-alkylation. The drawings of the compounds of formula (XIII) and (XVI) have been taken over from WO 97/21701 and the substituents in these drawings are as defined in WO 97/21701.

 

Figure US07572916-20090811-C00005

 

The synthesis of R115777 as originally described in WO 97/21701, is presented in scheme 1.

Herein, in step 1, the intermediate 1-methyl imidazole in tetrahydrofuran, is mixed with a solution of n-butyllithium in a hexane solvent to which is added chlorotriethylsilane (triethylsilyl chloride), followed by a further addition of n-butyllithium in hexane, the resulting mixture being cooled to −78° C. before the addition of a solution of a compound of formula (I), i.e. 6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone in tetrahydrofuran. The reaction mixture is subsequently brought to room temperature, and then hydrolysed, extracted with ethyl acetate and the organic layer worked up to obtain a compound of formula (II), i.e. (±)-6-[hydroxy(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone.

In step 2, the hydroxy compound of formula (II) is chlorinated with thionylchloride to form a compound of formula (III), i.e. (±)-6-[chloro(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone.

In step 3, the chloro compound of formula (III) is treated, with NH4OH in tetrahydrofuran to form the amino compound of formula (IV), i.e. (±)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone.

In step 4, the amino compound of formula (IV) is separated into its enantiomers by chiral column chromatography over Chiracel OD (25 cm; eluent: 100% ethanol; flow: 0.5 ml/min; wavelength: 220 nm). The pure (B)-fractions are collected and recrystallised from 2-propanol resulting in R115777, the compound of formula (V).

 

Figure US07572916-20090811-C00006

 

However, the procedure described in WO97/21701 has a number of disadvantages. For example, during the first step, the procedure results in the undesired formation of a corresponding compound of formula (XI), i.e. 6-[hydroxy(4-chlorophenyl)(1-methyl-1H-imidazol-2-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone), in which the imidazole ring is attached to the remainder of the molecule at the 2-position of the ring, instead of the desired 5-position. At the end of the procedure, this results in the formation of a compound of formula (XII), i.e. 6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-2-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone.

 

Figure US07572916-20090811-C00007

 

Furthermore, the purification of compound (V) using chiral chromatography is expensive and disadvantageous in view of the large amounts of solvent needed and the specialised equipment required to perform a large scale chiral chromatography.

Another process for the synthesis of R115777 as described in WO 02/072574, is presented in scheme 2.

Herein, in step 1, 1-methyl imidazole in tetrahydrofuran is mixed with a solution of n-hexyllithium in a hexane solvent to which is added tri-iso-butylsilyl chloride, followed by a further addition of n-hexyllithium in hexane. The compound of formula (I) in tetrahydrofuran is then added to the reaction mixture, keeping the temperature between −5° C. and 0° C. The resulting product of formula (II) is isolated by salt formation.

In step 2, the chlorination reaction is effected by treatment of the compound of formula (II) with thionyl chloride in 1,3-dimethyl-2-imidazolidinone.

In step 3, the chloro compound of formula (III) is treated with a solution of ammonia in methanol. After the addition of water, the compound of formula (IV), precipitates and can be isolated.

In step 4, the compound of formula (IV) can be reacted with L-(−)-dibenzoyl tartaric acid (DBTA) to form the diastereomeric tartrate salt with formula (VI) i.e. R-(−)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone [R—(R*,R*)]-2,3-bis(benzoyloxy)butanedioate (2:3).

Finally, in step 5, the compound of formula (VI) is treated with aqueous ammonium hydroxide, to form the crude compound of formula (V) which is then purified by recrystallisation from ethanol to the pure compound (V).

 

Figure US07572916-20090811-C00008
PatentSubmittedGrantedNOVEL IV FORMULATION OF TIPIFARNIB [US2009042935]2009-02-12
Novel IV formulation of tipifarnib [US2007093449]2007-04-26
Medical devices to treat or inhibit restenosis [US2005154451]2005-07-14
FARNESYL PROTEIN TRANSFERASE INHIBITORS WITH IN VIVO RADIOSENSITIZING PROPERTIES [WO0001411]2000-01-13
Patent Submitted Granted
Process for the preparation of imidazole compounds [US6844439] 2004-07-15 2005-01-18
TREATMENT OF MITOCHONDRIAL DISORDERS USING A FARNESYL TRANSFERASE INHIBITOR [US2010331363] 2010-12-30
TREATMENT OF MITOCHONDRIAL DISORDERS USING A FARNESYL TRANSFERASE INHIBITOR [US2011060005] 2011-03-10
Diastereoselective Synthesis Process with 6-Bromo-4-(3-Chlorophenyl)-2-Methoxy-Quinoline [US7572916] 2007-12-20 2009-08-11
Anti-cancer phosphonate analogs [US7452901] 2006-04-13 2008-11-18
Diastereoselective Synthesis Process for the Preparation of Imidazole Compounds [US7456287] 2007-10-11 2008-11-25
Diastereoselective Addition of Lithiated N-Methylimidazole on Sulfinimines [US7524961] 2007-12-20 2009-04-28
Therapeutic phosphonate compounds [US7645747] 2006-11-23 2010-01-12
TREATMENT OF PROTEINOPATHIES USING A FARNESYL TRANSFERASE INHIBITOR [US2010160372] 2010-06-24
ANTI-CANCER PHOSPHONATE ANALOGS [US2010022467] 2010-01-28
…………………………….
EXAMPLE A.1 a) Preparation of N-[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methylene)]-2-methyl-2-propanesulfinamide [(S(R)] (Compound 25)

Figure US07572916-20090811-C00019

 

Ti(OEt)4 (0.0162 mol) was added to a mixture of (4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (0.0032 mol) and (R)-(+)-2-methyl-2-propane-sulfinamide (0.0032 mol) in DCE (7 ml). The mixture was stirred and refluxed for 6 days, then cooled to room temperature. Ice water was added. The mixture was filtered over celite. Celite was washed with DCM. The organic layer was extracted with saturated sodium chloride. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. This fraction was purified by column chromatography over silica gel (40 μm) (eluent: DCM/MeOH/NH4OH 97/3/0.5), yielding 0.475 g of compound 25 (46%).

The compound N-[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methylene)]-2-methyl-2-propanesulfinamide [(S(S)] can be obtained in an analogous way.

b) Preparation of N-[(4-chlorophenyl)((4-(3-chlorophenyl)-2-methoxy-quinoline-6-yl)(1-methyl-1H-imidazole-5-yl)methyl]-2-methyl-2-propanesulfinamide [S(R)] (Compound 26)

Figure US07572916-20090811-C00020

 

n-Butyllithium (0.00081 mol) in hexane, was added dropwise at −78° C. to a mixture of 6-bromo-4-(3-chlorophenyl)-2-methoxy-quinoline (0.00081 mol) in THF (3 ml) under nitrogen flow. The mixture was stirred at −78° C. for 30 minutes. A solution of compound 25 (0.00065 mol) in THF (0.6 ml) was added. The mixture was stirred at −78° C. for 1 hour and 30 minutes, poured out into ice water and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. This fraction was purified by column chromatography over silica gel (40 μm)(eluent: DCM/MeOH/NH4OH 97/3/0.1). The pure fractions were collected and the solvent was evaporated, yielding 0.138 g (36%) of compound 26, melting point 153° C.

The compound N-[(4-chlorophenyl)((4-(3-chlorophenyl)-2-methoxy-quinoline-6-yl)(1-methyl-1H-imidazole-5-yl)methyl]-2-methyl-2-propanesulfinamide [S(S)] can be obtained in an analogous way

c) Preparation of (S)-1-(4-chlorophenyl)-1-[4-(3-chlorophenyl)-2-methoxy-quinoline-6-yl]-1-(1-methyl-1H-imidazole-5-yl)-methylamine (Compound 27)

Figure US07572916-20090811-C00021

 

Hydrochloric acid in isopropanol was added to a solution of compound 26 (0.000018 mol) in methanol (4.2 ml). The mixture was stirred at room temperature for 30 minutes. The mixture was added to potassium carbonate (10%) on ice and extracted with ethyl acetate. The organic layer was separated, washed with a solution of saturated sodium chloride, dried (MgSO4), filtered, and evaporated giving 0.086 g (100%) of compound 27, melting point 96° C., enantiomeric excess 88%.

d) Preparation of (S)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1H)-quinolin-2-one (Compound 28)

Figure US07572916-20090811-C00022

 

Compound 27 (0.00038 mol) in hydrochloric acid 3N (9.25 ml) and THF (9.25 ml), was stirred at 60° C. for 24 hours and evaporated, giving 0.18 g (100%) of compound 28, melting point 210° C.

EXAMPLE A.2 a) Preparation of N-[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methylene)]-p-toluenesulfinamide [(S(S)](Compound 29)

Figure US07572916-20090811-C00023

 

Ti(OEt)4 (0.0419 mol) was added to a mixture of (4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (0.0084 mol) and (S)-(+)-p-toluenesulfinamide (0.0084 mol) in DCE (18 ml). The mixture was stirred and refluxed for 7 days, then cooled to room temperature. Ice water was added. The mixture was filtered over celite. Celite was washed with DCM. The organic layer was extracted with saturated sodium chloride. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. This fraction was purified by column chromatography over silica gel (40 μm) (eluent: DCM/MeOH/NH4OH 97/3/0.5), yielding 1.15 g of compound 29 (38%).

The compound N-[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methylene)]-p-toluenesulfinamide [(S(R)] can be obtained in an analogues way.

B. Preparation of Final Compounds

EXAMPLE B.1 a) Preparation of (S)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone (Compound 30)

Figure US07572916-20090811-C00024

 

Compound 28 (0.00038 mol) was added to a solution of THF (1.8 ml) and NaOH 10N (1.8 ml). BTEAC (0.0019 mol) and methyliodide (0.00076 mol) were added and the mixture was stirred for 2 hours at room temperature. EtOAc was added. The organic layer was separated, dried (MgSO4), filtered, and evaporated giving 0.149 g (83%) of compound 30, enantiomeric excess 86%.

……………………………..
Cyclization of 3- (3-chlorophenyl) -N-phenyl-2-propenamide (I) by means of polyphosphoric acid (PPA) at 100 C gives 4- (3-chlorophenyl) -1,2,3,4-tetrahydroquinolin- 2-one (II), which is condensed with 4-chlorobenzoic acid (III) by means of PPA at 140 C to yield 6- (4-chlorobenzoyl) -4- (3-chlorophenyl) -1,2,3,4 -tetrahydroquinolin-2-one (IV). The dehydrogenation of (IV) by means of Br2 in bromobenzene at 160 C affords 6- (4-chlorobenzoyl) -4- (3-chlorophenyl) quinolin-2 (1H) -one ( V), which is methylated with iodomethane and NaOH / benzyltrimethylammonium chloride in THF to provide 6- (4-chlorobenzoyl) -4- (3-chlorophenyl) -1-methylquinolin-2 (1H) -one (VI). Condensation of compound (VI) with 1-methylimidazole (VII) by means of butyllithium in THF gives the triaryl carbinol (VIII), which is finally treated with ammonia in THF to afford R-115777.
………………………………
paper
Org. Lett., Article ASAP
DOI: 10.1021/ol503292p
Abstract ImageQuinolinone derivatives were constructed via a Pd-catalyzed C–H bond activation/C–C bond formation/cyclization cascade process with simple anilines as the substrates. This finding provides a practical procedure for the synthesis of quinolinone-containing alkaloids and drug molecules. The utility of this method was demonstrated by a formal synthesis of Tipifarnib.
synthesis

References

  1.  [1]
  2.  “R115777 in Treating Patients With Advanced Solid Tumors”
  3.  “R115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas”
  4.  R115777 New Drug Application

Angibaud, P.; Venet, M.; Filliers, W.; Broeckx, R.; Ligny, Y.; Muller, P.;Poncelet, V.; End, D. Eur. J. Org. Chem. 2004, 479.

see………….http://onlinelibrary.wiley.com/doi/10.1002/ejoc.200300538/abstract

(b) Filliers, W.; Broeckx, R.;Angibaud, P. U.S. patent, US7572916, 2009.

Share

Oleocanthal for treating pain

 Uncategorized  Comments Off on Oleocanthal for treating pain
Jan 062015
 

“Oleocanthal” is specifically deacetoxydialdehydic ligstroside aglycone, which exists as a single isomer (enantiomer). The (-)-enantiomer is the natural product and has the following chemical formula:

http://www.google.com/patents/EP2583676A1?cl=en

The Trustees of The University of Pennsylvania,

Monell Chemical Senses Center,

Russell S. J. Keast, Qiang Han, Amos B. Smith Iii, Gary K. Beauchamp, Paul A. S. Breslin, Jianming Lin,

  • In 1993, Montedoro and co-workers reported the isolation of a new class of phenolic compounds (1-4), including the dialdehydic and aldehydic forms of ligstroside (5) and oleuropeine (6) from virgin olive oils (Montedoro, G. et al. (1993) J. Agric. Food Chem. 41:2228-2234) (See Figure 1 for structures). These phenolic compounds comprise important minor constituents of virgin olive oils that have been implicated in the organoleptic characteristics including bitterness, pungency, and astringency (Andrewes, P. et al. (2003) J. Agric. Food Chem. 57:1415-1420 ).
  • In addition, these agents have been suggested to contribute to the oxidative stability of virgin olive oil and as such are associated with health benefits of olive oils, specifically their antioxidant/anticancer activities (Owen, R.W. et al. (2000) Food Chem. Toxicology 38:647-659; Owen, R.W. et al. (2000) Eur. J. Cancer 36(10):1235-1247; Baldioli, M. et al. (1996) J. Am. Oil Chem. Soc. 73(11):1589-1593; Manna, C. et al. (2002) J. Agric. Food Chem. 50(22):6521-6526).
  • Similar structural features have been reported in the constituents of the Jasminum (Somanadhan, B. et al. (1998) Planta Medica 64:246-50; Takenaka, Y. et al. (2002) Chem. & Pharm. Bull 50(3):384-389) and related plant species (Takenaka, Y. et al. (2002) Phytochemistry 59(7):779-787). It has been shown that both ibuprofen and a Mediterranean diet (i.e., high in olive oil) both decrease the risk/incidence for breast and lung cancer.
  • In 2003, Busch and co-workers at Unilever Research and Development Vlaardingen (The Netherlands) identified deacetoxydialdehydic ligstroside aglycone as a principal contributor to the potent pungent (burning) sensation at the back of throat associated with high quality virgin olive oils (Andrewes, P. et al. (2003) J. Agric. Food Chem. 57:1415-1420). Studies at Firmenich, Inc., reached the same conclusion (Firmenich, Inc. study). The structure of 1 was assigned,

    employing a series of 1 and 2D NMR experiments (Andrewes, P. et al. (2003) J. Agric. Food Chem. 57:1415-1420), in conjunction with comparison to literature data (Montedoro, G. et al. (1993) J. Agric. Food Chem. 41:2228-2234). The absolute stereochemistry remained undetermined. That 1 was responsible for the strong pungent (burning) sensation at the back of the throat was based on an extensive series of HPLC fraction analysis, omission analysis and correlation, and hydrolysis studies, in conjunction with human sensory studies. Andrewes et al., however, acknowledged that “a coelution compound causing the burning sensation” could not be eliminated without completing a synthesis of 1, which they stated to be “extremely challenging.”

EXAMPLES

 

Example 1: Isolation of deacetoxydialdehydic ligstroside aglycone “Oleocanthal”A. Synthesis of Oleocanthal

  • Retrosynthetically, we envisioned both enantiomers of (1) to derive from the enantiomeric forms of cyclopentanediols (7) via oxidative cleavage of the diol moiety (Scheme 1). The requisite cyclopentanediols (7) in turn would be prepared from cyclopentanones (+)- and (-)-(10), via alkylation to introduce stereoselectively the side chain from the convex face, followed by stereoselective Wittig ethylnation and removal of the acetonide moiety (Scheme 1).

    (5) Initially (+)- and (-)-cyclopentanones (10) were prepared via the sulfoximine and/or enzymatic protocols introduced and developed by Johnson (Johnson, C.R. and T. Penning (1988) J. Am. Chem. Soc. 110:4726-4735; Johnson, C.R. (1998) Acc. Chem. Res. 31:333-341). Although effective on modest scale (10-100mg), the requirement for gram quantities of the oleocanthals demanded that we secure for more scalable routes to (10). Towards this end, we optimized a hybrid of synthetic approaches (Moon, H. et al. (2002) Tetrahedron: Asym. 13(11):1189-1193; Jin, Y. et al. (2003) J. Org. Chem. 68(23):9012-9018; Yang, M. (2004) J. Org. Chem. 69(11):3993-3996; Palmer, A. et al. (2001) Eur. J. Org. Chem. 66(7):1293-1308; Paquette, L. and S. Bailey (1995) J. Org. Chem. 60:7849-7856) as outlined in Scheme 2. Importantly, both enantiomers of (10) could be prepared in multi-gram quantities in 7 steps, with an overall efficiency of 40% from inexpensive D-(-)-ribose. Key elements of both sequences entailed vinyl Grignard addition to the enantiomers of aldehyde (12), followed in turn by ring closing metathesis (RCM), PCC oxidation and hydrogenation (Scheme 2).

  • Alkylation of (+)- and (-)- cyclopentanone (10) with methyl bromoacetate was then anticipated to proceed from the less hindered convex face of the bicyclic skeleton to install the side chain in a stereoselective fashion. Initial attempts however to alkylate (-)-(8) with methyl bromoacetate employing LDA in the presence of HMPA furnished only a complex mixture containing only trace amounts of (-)-(16). Neither addition of Cu(I) (Johnson, C.R. and T. Penning (1988) J. Am. Chem. Soc. 110:4726-4735) reportedly to suppress side reactions, nor the use of the corresponding tin enolate [generated by treatment of (-)-(10) in THF with LDA, followed by HMPA and tributyltin chloride (Suzuki, M. et al. (1985) J. Am. Chem. Soc. 107:3348; Nishiyama, H. et al. (1984) Tetrahedron Lett. 25:223)] improved the situation. Alkylation of the zinc enolate of (-)-(10) [generated by treatment of (-)-(10) in THF with 1.1 eq. LHMDS, followed in turn by HMPA (3.0 eq.) and dimethyl zinc (Morita, Y. et al. (1989) J. Org. Chem. 54:1787-1788) (1.0 eq.)] with methyl bromoacetate, however consistently furnished (-)-(16) in 55-60% yield as a single diastereomer (this reaction was fairly clean except some baseline materials. Using t-butyl bromoacetate instead of methyl bromoacetate did not improve the yield) (Scheme 3).

  • Wittig ethylnation of (-)-(16) was next achieved with ethyltriphenylphosphine bromide. Best results were obtained employing LDA as the base at -45°C. Although excellent stereoselectivity (ca., 10:1 E:Z) favoring the E-isomer (-)-(17) was achieved, the yield was only modest (42%), presumably due to the ease of enolization of (-)-(16) (Edmunds, M. “The Wittig Reaction” In MODERN CARBONYL OLEFINATION, Takeda, Ed., John Wiley & Sons, New Jersey, 2004). Interestingly, the stereoselectivity varied dramatically with reaction temperature. At 0°C, the E:Z selectivity was 3.3:1, while at room temperature the selectivity was 1.6:1. Assignment of the E geometry of the olefin was based on NMR NOE analysis (Scheme 4).

  • Hydrolysis of ester (-)-(17) (LiOH/THF/H2O) next afforded acid (-)-(18), which was subjected to Mitsunobu esterification (Mitsunobu, O. (1981) Synthesis 1-28) with 4-hydroxyphenethyl alcohol to furnish phenol (-)-(19) in 92% yield. As expected, the Mitsunobu reaction proceeded with complete chemoselectivety at the primary hydroxyl (Appendino, G. et al. (2002) Org. Lett. 4:3839-3841). Completion of the synthesis of (-)-oleocanthal (1) was then achieved via liberation of the vicinal diol moiety (4N HCl/acetonitrile), followed by oxidative cleavage (NaIO4); (-)-oleocanthal (1) was identical in all respects (e.g., 1H and 13C NMR, IR and HRMS) with an authentic sample isolated from virgin olive oil, the latter possessing spectral data identical to that reported in the literature (Montedoro, G. et al. (1993) J. Agric. Food Chem. 41:2228-2234). The structural assignment of (1) was also confirmed by COSY NMR analysis. Synthetic (-)-(1) displayed a small negative optical rotation ([α]25D -0.78, c = 0.9, CHCl3) identical to that obtained from a sample isolated from virgin olive oil ([α]25 D -0.9, c = 2.0, CHCl3). Thus the stereochemistry of (-)-oleocanthal (1) is 3S, 4E. The enantiomer of the natural product (+)-(1) was prepared via a similar reaction sequence beginning with (+)-(10) to furnish (+)-1 ([a]25 D +0.73, c = 0.55, CHCl3) (Scheme 5).

  • In summary, an effective, scalable synthesis of both enantiomers of oleocanthal (1) has been achieved, each in 13 steps (7 % overall yield) from inexpensive (D)-(-)-ribose, requiring only 6 chromatographic separations. The structural similarity of oleocanthal to a number of related natural products (Somanadhan, B. et al. (1998) Planta Medica 64:246-50; Takenaka, Y. et al. (2002) Chem. & Pharm. Bull. 50(3):384-389; Takenaka, Y. et al. (2002) Phytochemistry 59(7):779-787) suggests that the synthetic approach presented here should also be applicable to their construction.

 

  • Figure 3 shows the synthetic scheme of (-)-oleocanthal.

  • Figure 4 shows the synthetic scheme of (+)-oleocanthal.

Share
 Older Entries  Newer Entries
Follow

Get every new post on this blog delivered to your Inbox.

Join other followers: