Indian Patent Office Rejects BDR Pharmaceutical’s Application for Compulsory License to Manufacture Anti-Cancer Drug Dasatinib

The Controller of Patents (Controller) vide order dated 29th October 2013, rejected BDR Pharmaceutical’s (BDR) compulsory license application against Bristol Meyer Squibb’s (BMS) anti-cancer drug Dasatinib. This was the second compulsory license application after Natco’s application for Nexavar.

Brief facts of the case: BDR filed an application on 4th March 2013 seeking grant of compulsory license for patent no: 203937 titled ‘A Compound 2-amino-thiazole-5-carboxamide’ granted to BMS and covering the active pharmaceutical ingredient of the drug Dasatinib. Prior to making an application for compulsory license, BDR initially sent a request to BMS for a voluntary license vide letter dated 2nd February 2012. In response to BDR’s request, BMS raised certain queries on BDR’s ability to manufacture and market the drug. BDR chose not to respond to the queries and filed an application for compulsory license before the Patent Office.

BDR claimed that patentee was employing delaying tactics by raising queries, which according to BDR could also be used against BDR in various legal forums. A suit for patent infringement filed by BMS against BDR is pending before the Delhi High Court. The Controller however observed that no query was specifically highlighted by the BDR that could adversely affect BDR’s position before this or any other legal forum. In the absence of reasoning / justification, Controller did not accept the arguments put forth by BDR.

When considering an application for grant of compulsory license under Section 84 of the Patent Act, the Controller is required to take into account whether credible efforts were made by the Applicant in obtaining a license from the patentee on reasonable terms and conditions and whether such efforts have not been successful, within a reasonable period as the Controller may deem fit. The ‘reasonable period’ has further been defined to mean a period not ordinarily exceeding a period of 6 months.

Controller further observed that the term ‘efforts’, under Section 84 of the Patent Act is not accompanied by the qualifying term ‘reasonable’ and the applicant ought to have appreciated that the duty cast upon the applicant to make ‘efforts’ is absolute and inflexible and without exceptions. In view of the above, the Controller held that BDR did not make enough efforts to obtain license from the patentee on reasonable terms and conditions and a prima facie case for grant of compulsory license has not been made out by the applicant. Accordingly the application was rejected.

It is open for BDR to either challenge this order of rejection before the Intellectual Property Appellate Board or re-negotiate a voluntary license with BMS and file a fresh application for compulsory license after six months.

Central Government Notifies Patents (Amendment) Rules 2013

The Central Government has notified Patents (Amendment) Rules 2013, effective from 15th October 2013.

Amendment paves way for the Indian Patent Office to officially start functioning as an International Search Authority (ISA) and International Preliminary Examining Authority (IPEA) under PCT from 15th October 2013. Applicants can now select the Indian Patent Office as the ISA while filing a PCT application. This will substantially reduce the cost incurred in filing the application from approximately USD 4000 (with EP as ISA) to around USD 1800 (which includes PCT filing of USD 1419 fees and Rs 10,000/- Indian ISA fees).

Under the amended rules, the Controller of Patents is now empowered to transfer patent applications between various patent offices in India. Under the previous rules applications could be prosecuted only through one of the four offices through which they were initially filed. There was no provision for transfer of files between various patent offices.

For biotechnology applications, applicants are now required to file sequence listings in text readable electronic format. Paper copies of sequence listings are not required. Applicants may thus avoid payment of fees on the extra pages containing sequence listing.

More details available on the Indian Patent Office website.

Indian Patent Office starts functioning as International Search and Examining Authority

Indian Patent office started functioning as the International Search Authority and International Preliminary Examining Authority under PCT since 15th October 2013. An Indian applicant can now select the Indian Patent Office as the ISA while filing a PCT application. This will substantially reduce the cost incurred in filing the application from USD 4000 (with EP as ISA) to around USD 1800 (which includes PCT filing fees and Rs 10,000/- Indian ISA fees).

As a practicing attorney, I am not too upbeat with the quality of search reports issued by the Indian Patent office though this may change with the added responsibilities of functioning as an ISA and IPEA. Neverthless the50% reduction in filing cost is certainly good news for Indian applicants who intend to file PCT applications. More details available on the Indian Patent office website.

IPAB rules on patentability of inventions comprising mathematical methods

Maths method

IPAB on July 5, 2013 ruled on the patentability of inventions comprising of mathematical methods in Electronic Navigation Research Institute Vs Controller General of Patents and Designs. The case was an appeal filed against the Deputy Controller’s decision to deny patent protection to 3624/DELNP/2005 which related to an invention comprising of a system for analyzing time series signals. The Controller held that the functions of the so-called system are based on a mathematical method for solving mathematical equations, and declined to accept the ‘technical effect theory’ followed under European Patent law, as he was of the opinion that our law does not allow patent for mathematical methods which have a technical effect. The invention was rejected as not patentable under S.3(k) of the Patents Act 1970.

The appellant’s patent application titled “A Chaos Theoretical Exponent Value Calculation System” pertained to a system for analyzing a time series signal by a method based on Chaos Theory and calculating a chaos theory exponent value (CTEV) thereof. The invention makes it possible to calculate CTEV that could not have been so far processed in a dynamics changing system and to perform the process at a high-speed and on a real-time basis. The inventor claims that conventional CTEV calculations systems assumes that the time series signal being analysed is stable and is not chaotic. Certain signals e.g. generic speech voice signals have temporarily changing dynamics because of a plurality of vowels that change the voice signals in a complex manner in a short period of time. The system claimed in the invention in short leads to better analysis of speech voice signals and has applications in speech synthesis applications.

 The appellants contended that the invention offers a non-obvious ‘technical solution’ to a technical problem of generic speech analysis and the invention ought to be patentable owing to the fact that Indian law generally follows the European Patent regulations. The ‘technical effect theory’ which is followed by the Boards of Appeal of the EPO, is that an invention is patentable if it provides a new and non-obvious “technical” solution to a technical problem. The problem, and the solution, may be entirely resident within a computer such as a way of making a computer run faster or more efficiently in a novel and inventive way.

 IPAB rejected the Appellants arguments and referred to the decision arrived at in Yahoo Vs. Rediff where it was held that “the inventive step must be a feature which is not an excluded subject itself. Otherwise, the patentee by citing economic significance or technical advance in relation to any of the excluded subjects can insist upon grant of patent thereto. Therefore, this technical advance comparison, should be done with the subject matter of invention and it should be found it is not related to any of the excluded subjects….” IPAB also noted the view taken by UK Courts in Gameaccount Ltd., T. 543/2006 where it was held that:

“…It cannot have been the legislator’s purpose and intent on the one hand to exclude from patent protection such subject matter, while on the other hand awarding protection to a technical implementation thereof, where the only identifiable contribution of the claimed technical implementation to the state of the art is the excluded subject-matter itself.”

 Thus it was held that invention which is the technical advance was itself nothing more than a “mathematical method” for solving mathematical claims, the identifiable subject matter itself was excluded subject matter under section 3(k) of the act. According, the controller’s decision was upheld and appeal was dismissed by the IPAB.

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Another Controversy laid to rest: Naturally ocurring DNA is patent ineligible but cDNAs are, rules US Supreme Court

are_your_genes_somebody_elses_propertyThe US Supreme Court, it seems, is on a mission to keep the biotech industry on its toes. After last month’s ruling in the Bowman Vs Monsanto case, the Court has delivered another landmark judgment yesterday in the AMP Vs Myriad Genetics  involving patents on BRCA1 and BRCA2 genes and diagnosis of breast cancer.

A unanimous ruling by 9 US Supreme Court judges have held that a naturally occurring DNA segment is a product of nature and therefore not patent eligible. However, they also clarified that complementary DNA or cDNA being a non-naturally occurring material is patent eligible.

Brief background on the case: It was a long known fact that occurrence of breast cancer in women was hereditary. Myriad discovered that two genes  i.e. BRCA 1 and BRCA 2 located on chromosomes 17 and 13 played an important role in the onset of breast cancer. Particularly they discovered that individual having mutations in the BRCA1 and BRCA2 genes were more susceptible to developing breast cancer. This information in turn enabled Myriad to develop medical tests that are useful for detecting mutations in a patient’s BRCA 1 and BRCA 2 genes and thereby assess whether the patient has an increased risk of breast cancer. Myriad sought and obtain a number of patents after this discovery.

Myriad’s patent gave it exclusive right to isolate and individual’s BRCA 1 and BRCA 2 genes and also to synthetically create a cDNA strand of the genes. In Myriad’s view, manipulating BRCA DNA in either of these fashions triggers its right’s to exclude others from making its patented invention. But isolation is necessary to conduct genetic testing and Myriad was not the only entity to offer BRCA testing after the genes were discovered. Petitioner Dr. Harry Ostrer, who was a medical practitioner, would routinely send his patients DNA samples to Pennsylvania’s Genetic Diagnostic Laboratory (GDL) which provided diagnostic testing for BRCA genes. After learning about GDL testing and Dr. Ostrer’s activity, Myriad sent them and other entities offering BRCA gene testing, letters asserting its patent. As a result, Dr. Ostrer along with medical patients advocacy groups, and other doctors, filed the present suit seeking a declaration that Myriad’s patents were invalid.

Gene

Claims of Myriad’s patents in question were essentially directed to a DNA segment that codes for the amino acids produced by BRCA 1 genes while dependent claims were directed to a cDNA molecule of the claimed DNA segment. A naturally occurring gene, which is a DNA segment, contains a mix of coding and non-coding regions called Exons and Introns.

One can identify coding and non-coding region of a gene by studying either the mRNA strand or the protein produced by the gene.  mRNA is produced by the body prior to translation to protein molecule, using the original gene segment as a template and contains only the coding region required to produce the protein. Scientist have been able to develop means to convert this mRNA strand, back to a DNA strand in laboratories using modern biotechnology techniques. The DNA strand so obtained is called cDNA or complementary DNA and this also contains only the coding region of the original gene.

Issue with the Myriad’s Patents: It was noted by the Court that Myriad did not dispute the fact that it neither created nor altered any of the genetic information encoded in the BRCA 1 and BRCA 2 genes. It was further observed by the Court that Myriad’s principal contribution lay in uncovering the precise location and genetic sequence of the BRCA 1 gene and BRCA 2 gene within chromosome 17 and 13. This discovery by itself does not render the BRCA genes new ‘compositions of matter’ that are patent eligible. Besides, Myriad’s patent description simply details the routine biotech process using which Myriad was able to narrow down onto the location of the BRCA genes.

As far as claims of Myriad patents are concerned, the Court observed that they primarily focus on the information contained in the genetic sequence and not with the specific chemical composition of any particular molecule. The Court also observed that there were no method claims, claims to application concerning the new knowledge on BRCA genes or DNA segment in which order of naturally occurring nucleotides are altered, asserted before this court.  In view of these observations, the Court held that genes and the information coded by them are patent ineligible as they are simply isolated from the surrounding genetic material. The Court also clarified that cDNA, being a non-naturally occurring molecule, forms part of patent eligible subject matter. Court observed that creation of cDNA sequence from mRNA results in an exon-only molecule that is not naturally occurring. Hence, cDNA does not present the same obstacles to patentability as naturally occurring isolated DNA segments.

The above decision only invalidates Myriad’s claim to BRCA DNA segments but does not affect Myriad’s other patents that relate to BRCA gene analysis and tests. The ruling also does not affect claims directed towards cDNA or synthetic DNA. However, the ruling does allow other companies to offer BRCA gene testing services and seek second opinion, which was what at the heart of this controversy.

Source: Association for Molecular Pathology v. Myriad Genetics, U.S. Supreme Court, No. 12-398

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Curious case of Monsanto’s GMO seeds

Last month, the US Supreme Court issued its ruling in the Bowman Vs Monsanto case, siding with Monsanto and in a unanimous decision, ruled that the doctrine of patent exhaustion does not affect Monsanto’s right to restrict farmers from reproducing or making new copies of patented articles i.e. Monsanto’s roundup ready seed varieties. The victory however may be short-lived for as reported by Forbes here, illegal genetically modified wheat has been found in a farm in Oregon. A Kansas based farmers, possibly frustrated with the discovery of accidental contamination, has sued Monsanto claiming negligence on part of Monsanto in controlling its Roundup ready technology.

Facts of the Bowman Vs Monsanto: 

The exhaustion doctrine, also referred to as the first sale doctrine, is a common law patent doctrine that limits the extent to which patent holders can control an individual article of a patented product after an authorized sale. Under the doctrine, once an unrestricted, authorized sale of a patented article occurs, the patent holder’s exclusive rights to control the use and sale of that article are exhausted, and the purchaser is free to use or resell that article without further restraint from patent law.

Monsanto invented and patented the Roundup Ready technology which comprises of making genetic alteration to plant seeds which allows the resultant plants from the seed to survive exposure to the herbicide glyphosate. Monsanto sells soybean seeds comprising the roundup ready genetic alteration subject to a licensing agreement that permits farmers to plant the purchased seed in one, and only one, growing season. Growers may consume or sell the resulting crop from the seed, but may not save any of the harvested soybeans for replanting. Petitioner Bowman purchased Roundup Ready soybean seed for his first crop of each growing season from a company associated with Monsanto and followed the terms of the licensing agreement. But to reduce costs for his riskier late-season planting, Bowman purchased soybeans intended for consumption from a grain elevator; planted them, harvested the resulting soybeans that contained that trait; and saved some of these harvested seeds to use in his late-season planting the next season. After discovering this practice, Monsanto sued Bowman for patent infringement. Bowman raised the defense of patent exhaustion, which gives the purchaser of a patented article, or any subsequent owner, the right to use or resell that article. The District Court rejected Bow­man’s defense and the Federal Circuit affirmed.

The Courts while delivering judgement clarified the applicability of the doctrine in biotech related matters and held that Patent exhaustion does not permit a farmer to reproduce patent­ed seeds through planting and harvesting without the patent holder’s permission. Under the patent exhaustion doctrine, “the initial authorized sale of a patented article terminates all patent rights to that item,” (Quanta Computer, Inc. v. LG Electronics, Inc., 553 U. S. 617, 625), and confers on the purchaser, or any subsequent owner, “the right to use or sell” the thing as he sees fit, (United States v. Univis Lens Co., 316 U. S. 241, 249–250). However, the doctrine restricts the patent­ee’s rights only as to the “particular article” sold, and it leaves untouched the patentee’s ability to prevent a buyer from making new copies of the patented item. By planting and harvesting Monsanto’s patented seeds, Bowman made additional copies of Monsanto’s patented invention, and his conduct thus falls outside the protections of patent exhaustion. Were this otherwise, Monsanto’s patent would provide scant benefit. After Monsanto sold its first seed, other seed companies could produce the patented seed to compete with Monsanto, and farmers would need to buy seed only once. The court further explained that the “right to use” a patented article following an authorized sale, “does not include the right to construct an essentially new article on the template of the original, for the right to make the article remains with the patentee.” Accordingly, Bowman could not “‘replicate’ Monsanto’s patented technology by planting it in the ground to create newly infringing genetic material, seeds, and plants.

Coming back to the Wheat issue: Genetically modified wheat is not approved by US FDA and therefore is not available for commercial sale in US or for that reasons any other part of the world. Though Monsanto had tested the roundup ready wheat and applied for a US FDA approval, it did not actively pursue the application since US farmers were averse to embrace GMO wheat. Concerns partly were due to ban on exports of wheat from USA since a major chunk of wheat grown on US soils is exported to countries who are either averse or have zero tolerant policy towards GMO crops.

The contamination of Oregon farms with GM wheat may have resulted due to rogue seeds being carried by wind or any other natural phenomena, or may have resulted due to human error, as theorized by Forbes,but no knows for sure what exactly has happened. While it may seem unreasonable to hold Monsanto liable for a natural process of pollination and the natural process of self replication, which is difficult to control, it is the very same natural processes which have been at the center of controversy in the various cases, including Bowman Vs Monsanto, wherein Monsanto has tried to assert its patent rights and prevailed in a few.

With the above background in place, I am looking forward as to what the courts have to say in the matter.

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Supreme Court rules Novartis’s cancer drug, not an ‘Invention’ under the Patents Act

ImageNews is out, Supreme Court has finally pronounced its verdict in the ‘Glivec’ matter. In a 112 page judgement, Mr. Justice Aftab Alam and Ms. Justice Ranjana Prakash Desai rejected Novartis’s application on grounds that the beta crystalline form of Imatinib Mesylate, sought to be patented by Novartis, does not qualify the test of invention laid down in clause (j) and (ja) of section 2(1) and section 3(d) of the Patents Act, 1970.

Novartis’s application for patent 1602/MAS/1998 was earlier rejected by the patent office, on grounds of lacking novelty, inventive step and being unpatentable in view of section 3(d). Novartis challenged Controller’s decision in a writ petition before the Madras High Court. The matter was transferred to the Intellectual Property Appellate Board which also rejected Novartis’s patent on grounds of being unpatentable under section 3(d) and under 3(b) the invention being against public order and morality. IPAB however acknowledged the novelty and inventive step requirements for the invention. Novartis also challenged the constitutional validity of section 3(d) before the Madras High Court, this please however was also rejected.

Issues that were to be decided by the Court in this judgment were as follows:

  • What is the true import of section 3(d) of the Patents Act, 1970
  • The interplay of section 3(d) with definition of invention under the Patents Act, 1970.
  • Does Novartis product qualify as an invention under the Patent Act. If yes, can patentability still be questioned under section 3(d) of the Patent Act

Definition of Invention: On the definition of invention under the Patents Act, Justice Aftab Alam of the Supreme Court, noted the following in paragraph 90:

“On a combined reading of clauses (j), (ac) and (ja) of section 2(1), in order to qualify as “invention”, a product must, therefore, satisfy the following tests:

i)         It must be ‘new’;

ii)       It must be ‘capable of being made or used in an industry’;

iii)      It must come into being as a result of an invention which has a feature that:

  • Entails technical advance over existing knowledge; OR
  • Has economic significance; AND
  • Makes the invention not obvious to a person skilled in the art.

Justice Aftab Alam further observed that:

“Para 92. Section 3 is in Chapter II of the Act, which initially contained section 3, 4 and 5, but after the deletion of section 5 with effect from January 1, 2005, Chapter II has only two sections: section 3 and 4. The Chapter has the Heading “Inventions Not Patentable” and section 3 has the marginal heading ‘What are not Inventions’. As suggested by the Chapter heading and the marginal heading of section 3, and as may be seen simply by going through section 3, it puts at one place provisions of two different kinds: one that declares that certain things shall not be deemed to be ‘inventions’ (for instance clauses (d) & (e)]; and the other that provides that, though resulting from invention, something may yet not be granted patent for other consideration (for instance clause (b)]

Section 3(d): Finally in relation to the issue of import of section 3(d) into the Patents Act, 1970 and interplay of section 3(d) with the definition of invention, the Court after analyzing the history of the Patent Act and legislative amendments made thereto, held that:

“Para 104. We have so far seen section 3(d) as representing ‘patentability’, a concept distinct and separate from ‘invention’. But if clause (d) is isolated from the rest of section 3, and the legislative history behind the incorporation of Chapter II in the Patents act, 1970, is disregarded, then it is possible to see section 3(d) as an extension of the definition of ‘invention’ and to link section 3(d) with clauses (j) and (ja) of section 2(1). In that case, on reading clause (j) and (ja) of section 2(1) with section 3(d) it would appear that the Act sets different standards for qualifying as ‘invention’ things belonging to different classes, and for medicines and drugs and other chemical substances, the Act sets the invention threshold further higher, by virtue of the amendments made in section 3(d) in the year 2005.”

The Patent Act allows grant of patent for product that are new and inventive but new product may not necessarily mean something completely new, one which was not existing before. However, in case of pharmaceuticals, if a product for which patent is sought is a new form of a known substance, that the invention must pass the additional test laid down in section 3(d) i.e. the test of enhanced efficacy.

What is Efficacy?: While answering the question as to what is efficacy, the Court observed, that the test of efficacy would depend upon the function, utility or the purpose of the product under consideration, and held that “Therefore, in the case of a medicine that claims to cure a disease, the test of efficacy can only be “therapeutic efficacy”.”  The Court further observed that mere change of form with properties inherent to that form would not qualify as ‘enhancement of efficacy’ of a known substance. The Court however refused to rule on the exact scope of “therapeutic efficacy” and left it to be determined by future courts on a case by case basis.

Decision on Novartis Patent: While deciding on the issue as to whether Novartis’s product qualify as an invention under the Patent Act, the Court observed that Gleevec directly emanates from the Zimmermann patent (prior art) since, the appellant i.e. Novartis has maintained that Gleevec (Imatinib Mesylate) is part of the Zimmermann patent. Novartis obtained drug approval (US) for Gleevec on that basis, it claimed an extension of the term of the Zimmermann patent for the period of regulatory review for Gleevec and stopped Natco Pharma Ltd. from marketing its drug in the UK on the basis of the Zimmermann patent. Further, US board of appeals, in its judgment granting patent for the beta crystal form of Imatinib Mesylate, proceeded on the basis that Zimmermann patent might have covered the beta crystal form of Imatinib Mesylate, however there was no teaching for making of Imatinib Mesylate from Imatinib, and for its use in pharmacological composition for treatment of tumors and thus the appellant is fully bound by the finding and cannot be heard to take any contrary plea.

In view of the above findings, the Court concluded that Imatinib Mesylate is a known substance from the Zimmermann patent and cannot be said to be a new product, having come into being through an ‘invention’ that has a feature that involves technical advance over the existing knowledge and that would make the invention not obvious to a person skilled in the art.

On the question of applicability of section 3(d) the Court observed that beta crystal form being a polymorph, Novartis invention also needs to qualify the additional test of ‘enhanced efficacy’ laid down in section 3(d). On this, the Court noted from appellant’s patent specification that pharmacological properties possessed by the beta crystal form of Imatinib Mesylate are equally possessed by Imatinib in the free base form or its salt. Since, Imatinib Mesylate is a known substance, Novartis was obliged to show enhanced efficacy of the beta crystal form over Imatinib Mesylate (non-crystalline). There is however no material in the subject application or in the supporting affidavits to make any comparison of efficacy, or solubility, between the beta crystal form of Imatinib Mesylate and Imatinib Mesylate (non-crystalline).The Court further noted that the additional properties of the beta crystal form such as (a) more beneficial flow properties; (b) better thermodynamics stability; and (c) lower hygroscopicity; as pointed out by the Appellant, are physical attributes that would give the subjected product improved processability and better and longer storability. However, on the basis of those properties, the beta crystal form cannot be said to possess enhanced efficacy over Imatinib Mesylate.

In view of the above findings, the Court held that Novartis application for patent for the beta crystalline form of Imatinib Mesylate fails the test of invention and patentability as laid down in clauses (j), (ja) of section 2(1) and section 3(d) and accordingly the appeal was dismissed with cost to the Appellant.

The judgment clarifies, though not entirely, the interpretation of the controversial section 3(d) of the Indian Patent Act which sets up a second tier of qualifying standards for chemical and pharmaceutical products. Section 3(d) provides:

“the mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any new property or new use for a known substance or of the mere use of a known process, machine or apparatus unless such known process results in a new product or employs at least one new reactant” [is not an invention within the meaning of the Patents Act.]

The proviso to Section 3(d) states that:

“For the purposes of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy.”

In light of the Supreme Court judgement the term ‘efficacy’ referred to in section 3(d) is to be construed only as ‘therapeutic efficacy’ in case of pharmaceutical and medicinal products. Thus claims to polymorphs or enantiomers of known chemical compounds, having enhanced properties, such as bioavailability or reduced toxicity, which do not have a direct bearing on the ‘therapeutic efficacy’ of the compound vis-à-vis the known compound, will not qualify under section 3(d) of the Patent Act and hence will not be termed as inventions within the meaning of the Patent Act.

Likelihood of Issuance of New Compulsory Licenses under the Indian Patent Act

There have been news reports here and here of the likelihood that a compulsory license may be issued by the Government of India for three cancer drugs – Trastuzumab, Dasatinib and Ixabepilone. Out of the three cancer drugs in question, Dasatinib and Ixabepilone are small molecule drugs whereas trastuzumab is a biologic.

Provisions for issuance of Compulsory License under the Patent Act:

Under the Patent Act, a compulsory License can be issued either under section 84 or 92 of the Patent Act. Section 84 requires applicant to establish that, reasonable requirements of the public with respect to the patented invention have not been satisfied or the patented invention is not being made available at an affordable price to public in India. This is what happened in Bayer and Natco’s case. Under section 92, Government can notify a patent for issuance of compulsory license if any of the following 3 conditions are met: 1) National Emergency; 2) Cases of extreme urgency; or 3) In the case of public non-commercial use. Once the central government has issued a notification under section 92, any person interested may approach the controller for a compulsory license. The process becomes much simpler as the applicant does not have to establish that reasonable requirement of the public are not met.

Additionally, the under section 100, the Central Government can authorized any person in writing to use an invention for the purposes of the government. The right to use an invention under this section includes right to sell, on a non-commercial basis, the goods which have been made in exercise of that right. Section 99 defines used by the government to mean if it is made, used, exercised or vended for the purposes of the Central Government, a State Government or a Government undertaking.

Can Pharma Companies Oppose this Compulsory License?

Decisions, orders and directions issued by the Controller or the Central Government under section 92 of the Patent Act can be appealed before the Intellectual Property Appellate Board, whereas decision/direction under section 100 is not.

Issues:

Incase of Trastuzumab generic version are already available and marketed by Roche as well Emcure, at reduced price points in the Indian market. Grant of compulsory license on grounds of public non-commercial use, atleast on this drug will be fraught with many issues in view of the lower priced generic versions. Further, Traztuzumab being a biologic and being structurally more complex in comparison to the small drug molecules, is difficult, though not impossible to reproduce as it is extracted from cell culture using modern biotech techniques. Growing conditions of the cell culture can have major impact on the function and quality of the final biologic product.

No further details regarding the terms of the compulsory license or even a gazette notification by the Government of India on the three cancer drugs is available at this stage. However, the news has generated considerable buzz and apprehensions in the pharma industry and is bound to make a few companies rethink their business strategy in India.

Draft Guidelines for Examination of Biotechnology Related Inventions Published by the Indian Patent Office.

In one of my earlier post on gene patents, I had stressed need for adequate guidelines on dealing with application for biotechnology related inventions. The Controller General of Patent Design and Trademarks has now published draft guidelines detailing the manner in which application for biotech related inventions are to be examined.

Some important points to be noted from the guidelines are as follows:

Under the new guidelines, it has been clarified that claim to a polynucleotide or protein sequence, that was available as part of a library before the priority date, shall be interpreted to have lacked novelty. The reason given to support this interpretation is that the earlier (library) sequence inherently possesses the activity of the claimed sequence. The guidelines further clarify that product such as nucleic acid sequences, proteins, enzymes, etc which are directly isolated from nature are not patentable subject matter under section 3(c) of the Patent Act. This essentially precludes patent on genes which are identified, purified and made available in an isolated from, since genomes of practically every species including human genome have been sequenced and are now available in online searchable libraries.

Claim to an isolated sequence of nucleic acids or protein which is not hit by the above mentioned hurdle, shall require identification of its usefulness (to prove industrial applicability) and provide enabling disclosure on a practical way of using it, in the specification.

Methods in which human embryos are used for commercial exploitation will be termed as invention contrary to public order and morality and hence unpatentable under section 3(b). The explanation to this guideline however renders method in which even human embryonic cell lines are used, unpatentable. Embryonic cell lines are used in a variety of research areas especially screening of chemicals and compounds that can affect a fetus during gestation. Thus inventions not directed towards cloning or germ line modification may also be included under the ambit of section 3(b) if they happen to use embryonic stem cell lines.

Though the above are draft guidelines, I would not be surprised if the same are finalised without any modfications as it happend with guidelines issued for dealing with inventions related to traditional knowledge. Nevertheless, comments and suggestions, if any, can be sent to the Controller General of Patent Design and Trademark by 11th January 2013. The publication notice and the draft guidelines can be accessed here and here.

Invalidation of Roche’s Pegasys Patent. Was insufficient disclosure to blame?

The Intellectual Property Appellate Board set aside, grant of Indian Patent No: 198953 to F. Hoffmann-La Roche AG in an appeal after the Controller upheld, validity of the patent in a post-grant opposition. The grant was set aside on grounds that invention claimed is obvious in view of the prior arts cited and also, it does meet requirements of section 3(d) of the Patent Act.

The patent relates to one of Roche’s important biological drugs ‘Pegasys’ which is a pegylated form of Interferon alpha used for treatment of Hepatitis C. The 1997 application was published in 2006 after which post-grant oppositions were filed by M/s. Wockhardt and Sankalp. Controller (T.V. Madhusudhan) had upheld validity of the patent during post grant opposition.

The invention claimed in the patent relates to a class of proteins called ‘Interferons’ which are produced by the body against pathogens such as bacteria and viruses and play a pivotal role in body’s immune mechanism. It is pharmaceutically active and used in the treatment of Hepatitis-C. Unmodified Interferon alpha has several disadvantages such as rapid absorption and removal from the body, degradation by proteolytic enzymes due to which it has a low serum half-life of 4 to 6 hours. Further, all foreign proteins when injected into the body, elicit some immune response though the degree of such response may vary considerably. In order to overcome the disadvantages, proteins is conjugated to a polymer called polyethylene glycol (PEG). This improves stability, solubility and reduces immunogenicity of the conjugated protein when administered into the body.

Pegylation is the process of attachment of one or more PEG chains to another molecule.The site and amount of

pegylation are key factors in determining the activity of a conjugated protein. The amount and site of pegylation can elicit different pharmacokinetic responses, even in the same protein molecules. Interferon possess multiple sites for pegylation and attachment at each of this different sites could have given pegylated interferon, albeit with different pharmacokinetic properties.

Claim 1 of the invention claims a branched PEG (polyethylene glycol) Interferon alpha conjugate having the formula

Formula I

wherein R and R’ are independently lower alkyl, X is NH or O; n and n’ are integers having a sum of from 600 to 1500; and the average molecular weight of the PEG unit is between 26,000 daltons to 66,000 daltons.

The protein conjugate described in the present invention has two linear PEG molecules attached to a single site on Interferon alpha. The advantage of this configuration provides a PEG conjugate with double the PEG mass without having multiple sites of pegylation. The resultant branched PEG interferon conjugate according to the invention, shows enhanced therapeutic activity in comparison to native Interferon as well as liner PEG interferon conjugate (which were already known at the time invention was made).

While deciding on the obviousness issue, Justice Prabha Sridevan observed the following

From the patent specification: (a) Interferons were known to be pharmaceutically active against Hepatitis C; (b) It was known that PEG conjugated proteins have certain clinically useful properties which are better physical and thermal stability, protection against enzymatic degradation, increased solubility, longer in-vivo half-life, and decreased clearance and enhanced potency. PEG conjugated proteins were also known to have reduced immunogenicity and antigenicity. (c) Pegylated interferons had a higher anti-proliferative activity was also known prior to the invention. Based on the above, she concluded the following in relation to the conjugates claimed in the invention, “These are admittedly common general knowledge on the date of invention and therefore improved activity could not have been a surprise it was expected”.

She further observes that the Prior arts disclosed use of higher molecular weights PEG molecules to increase circulation time, activity and to reduced immunogenicity of the administered protein conjugates; Prior arts, particular Mofardini, which was also referenced in the patent’s specification, disclosed branched PEG conjugates of enzymes, having similar structure of the branched PEG molecule disclosed in the Patent, which showed marked improvements over liner PEG conjugates of such enzymes. Thus, a person skilled in the art could have used conventional methods to arrive at the conjugates of the present invention using information available in the prior arts. The results were predictable and there was no surprising effect. She particularly commented that “Even if one grants a degree of unpredictability in the behavior of interferon (vis-à-vis the enzyme), there was a greater reason to expect success since interferon had positively responded to liner PEG conjugates”. In view of the above, novelty was acknowledge however the invention claimed in the Patent was held to be obvious and grant of the Patent was set aside

It may be argued that teachings of Mofardini only relate to pegylated enzymes and not interferons which are completely different in structure, activity and function, hence teachings of Mofardini, cannot be said to have rendered pegylated interferons of the present invention obvious. Though Roche’s patent talks in detail about the size and structure of the PEG molecule used to create PEG conjugated interferon, it contains little information with regard to the site of attachment for the PEG molecule except that it mentions that they may be attached to a primary amino groups on lysine or  the Hydroxyl group on serine or N-terminus of Interferon alpha. Was some crucial piece of information left out from the specification which could have enabled Roche to better describe its inventive contribution in the field of pegylated interferons? May be or may be not, but for now what is to be seen is whether Roche will prefer any further proceedings against the IPAB judgement or accepts the doomed faith of Indian Patent No: 198953.