TWN Info Service on Health Issues (Apr25/01)
2 April 2025
Third World Network

IP: Gilead amend Lenacapavir patent claims in attempt to save “patent evergreening” application

New Delhi, 2 April  (Prathibha Sivasubramanian)  – Gilead Sciences has narrowed its patent claims on Lenacapavir (LEN) following opposition from civil society organizations (CSOs).

LEN, a long-acting HIV treatment requiring twice-yearly injections, has been approved in the United States and the European Union since 2022. It has also shown promise for HIV prevention (PrEP). While the drug offers significant therapeutic benefits, concerns persist over high pricing and restrictive licensing in low- and middle-income countries. Gilead’s multiple patent applications to extend exclusivity have raised fears of “patent evergreening” and delayed generic competition.

Patent Applications and Opposition

Gilead has filed numerous LEN-related patents in many countries, including 14 in India, covering its Markush (a general formula with variable substitutions), compound structure, salts, crystalline forms, and prodrugs.

CSOs have so far opposed five patent applications on LEN.  Among these five pre-grant oppositions two key applications are IN202017007904 (choline salt) and IN202017010006 (sodium salt), being claims on different chemical forms of the same drug, LEN. These variations do not change how the drug works but may slightly alter properties like stability or how the drug is absorbed. CSOs argue that these applications are part of an attempt to prolong monopoly rights without significant therapeutic advancement.

The Indian Patent Office (IPO) objected to both applications, citing prior art and insufficient efficacy data under Section 3(d) of the Patents Act, a provision that disallows patents for minor modifications of known or existing drugs or chemical substances without real therapeutic benefits. In its First Examination Report, the IPO noted that LEN’s choline and sodium salts, along with their crystalline forms, had been previously disclosed. Without comparative data proving enhanced efficacy, the applications were deemed ineligible for patent protection.

[A First Examination Report is the first official review of a patent application by the patent office to assess whether the claimed invention meets legal requirements, including novelty, an inventive step, and qualitative improvement over existing knowledge. Such Report is issued under Section 12(1) of the Indian Patents Act, 1970.

[In the context of patent law, "prior art" refers to any publicly available information or evidence that existed before the effective filing date of a patent application, which can be used to determine if an invention is novel and non-obvious. Establishment of prior art negates a patent application.

[Section 3(d) of the Patents Act, 1970 reads: “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.

[Explanation. —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”.]

The IPO also raised objections under Section 3(e) – a provision that denies patents for combinations of known substances unless the combination demonstrates an effect greater than the sum of the individual substances' effects – for lack of specific ingredient ratios, as well as under Section 10 for insufficient disclosure. The broad claims in the applications were not fully supported, with only three examples provided

[Section 3(e) of the Patents Act 1970 on what are not inventions: "a substance obtained by a mere admixture resulting only in the aggregation of the properties of the components thereof or a process for producing such substance; …"]

For the sodium salt application (IN202017010006), the IPO found the claims to be unclear, using broad and flexible terms that did not meet the clarity requirement under Section 10(4). This is a provision that prohibits vague or overly broad claims, requiring the invention to be described clearly so that any person skilled in the field can understand and replicate it without ambiguity or uncertainty. Additionally, the crystalline forms were vaguely labelled as I, II, III, etc., without a clear scientific definition.

[Section 10(4) reads: “The complete specification shall— (a) fully and particularly describe the invention and its operation or use and the method by which it is to be performed; (b) disclose the best method of performing the invention which is known to the applicant and for which he is entitled to claim protection; (c) set forth the claims defining the scope of the invention; (d) be accompanied by an abstract to provide technical information about the invention.]

Gilead’s Response and Claim Amendments

Following the IPO’s First Examination Report objections, Gilead reduced its claims on the choline salt (IN202017007904) from 45 to 26, arguing that the form was not explicitly disclosed in prior art. The company contended that Section 3(d) did not apply since no known substance existed on the priority date.

Similarly, for the sodium salt (IN202017010006), Gilead limited the claims from 80 to 49 and argued that LEN’s salts and crystalline forms were not explicitly disclosed in prior art. As the prior art documents did not directly reference LEN, Gilead asserted that Section 3(d) was inapplicable.

Staggering Filing Dates for Extended Monopoly

LEN’s compound patent application (WO/2018/035359) was filed in August 2016. Before its publication, Gilead filed patents for the choline (WO/2019/035973) and sodium (WO/2019/035904) salts in August 2017. Although Gilead had developed these salts by 2013, it withheld explicit disclosure, filing successive applications over time to prolong patent protection and delay generic competition.

A document is considered prior art only if published before the priority date of the examined application. By staggering patent filings, Gilead ensured that its LEN compound patent would not serve as prior art against later applications. This strategy, known as evergreening, allows companies to extend exclusivity beyond the original patent term.

Oppositions and Evergreening Concerns

Opponents argue that Gilead's LEN salt and crystalline form patent applications are an attempt at evergreening, extending exclusivity until 2038. They claim LEN and its forms are already covered by an existing Markush patent, prior art describes LEN formulations, and no enhanced efficacy has been proven as required under Section 3(d). They also note that no comparative evidence distinguishes LEN salts from GS-CA1, a similar analogue developed by Gilead.

Pre-grant Opposition Hearing and Legal Precedents

Hearings for LEN’s salts and crystalline forms were scheduled for August 2024 but faced multiple adjournments, including those requested by Gilead. Final hearings took place in November 2024. The outcome will be crucial in determining whether generic manufacturers can produce affordable alternatives to Gilead’s product.

Gilead maintains that Lenacapavir is covered under the Markush patent, implying unauthorized production could be an infringement. However, if this argument prevails, prior Markush-based applications would be excluded as prior art, allowing Gilead to secure additional patents on essentially the same invention.

The Indian Supreme Court has previously ruled against such tactics, emphasizing the distinction between coverage (claims) and disclosure (enablement). It ruled that conflating the two would grant exclusivity over undisclosed inventions, undermining the fundamental balance of the patent system. As stated by the Supreme Court in Novartis AG v. Union of India (2013):

“We certainly do not wish the law of patent in this country to develop on lines where there may be a vast gap between the coverage and the disclosure under the patent; where the scope of the patent is determined not on the intrinsic worth of the invention but by the artful drafting of its claims by skillful lawyers.”

Post-Hearing Developments

Following the Opposition hearing and a prosecution hearing under Section 14 of the Patents Act (which allows the applicant to address objections raised in the First Examination Report before the Patent Controller), Gilead significantly narrowed its claims. The sodium salt application was reduced from 49 claims to a single claim, covering only its crystalline form, while the choline salt application was restricted from 26 claims to 15.

Additional oppositions have been filed; however, under new rules, new opponents must first establish a prima facie case before the patent controller. Furthermore, High Court rulings now require opponents to rely on different prior art documents than those cited by the IPO or earlier opponents, making the opposition process more complex.

[The First Examination Report objections are generally broader than the Opposition grounds. So, the Applicant is given a separate hearing before the Controller.]

Recently, Argentina’s National Institute of Industrial Property rejected Gilead’s patent for LEN, ruling it was already disclosed in an earlier Markush patent. This contradicts Gilead’s claim that LEN was a new compound. Under Section 8 of India’s Patents Act, the IPO must consider decisions on corresponding foreign applications. Given India and Argentina’s higher patentability standards, the IPO should reject Gilead’s salt and crystal patent applications.

Conclusion

The LEN patent oppositions highlight concerns over patent evergreening, as Gilead attempts to extend monopoly rights through minor modifications without proving enhanced efficacy. The reliance on coverage over disclosure conflicts with Indian Supreme Court precedent. While Gilead’s amendments aim to overcome objections, legal scrutiny persists.

The outcome of these proceedings will shape future patentability standards for pharmaceutical salts and crystalline forms, influencing access to affordable HIV treatment worldwide.