Patenting Repurposed Drugs

By John E. Conour --

Even with billions of dollars of funding and the cumulative knowledge and experience of over a hundred years of experimental pharmacology, de novo discovery of effective and safe therapeutics remains a costly and risky endeavor.  The number of unsuccessful attempts to obtain Food and Drug Administration (FDA) approval of drugs for specific indications is far greater than the number of successes.  As a result, there is an extensive and ever growing list of "failed" drugs, most of which are ultimately abandoned by pharmaceutical companies.

More recently, failed drugs previously considered to be lost causes are being reconsidered as possible therapies for different indications than those for which they had originally been considered.  Such drug "repurposing" provides researchers and clinicians with a cost-effective way to identify potential new therapies without needing to start from scratch.  Many failed drugs have already established their relative safety in Phase I clinical trials, which can simplify and reduce the cost of obtaining FDA approval should a new indication be found.  Drug repurposing is not limited to failed drugs but is also being considered for currently marketed drugs as well as "off patent" generic compounds to expand and extend their usefulness.

But because drug repurposing primarily concerns previously-known drugs, obtaining patent protection can be challenging.  In some cases, a drug to be repurposed is still protected by a patent that can be acquired and/or in-licensed, but often the drug itself is not protected by patent.  Without patent protection, commercialization of a repurposed drug (i.e., maximizing the potential beneficial impact of the drug) is not realistic.  This article discusses certain issues to be considered when trying to obtain new patent protection for repurposed drugs.  It should be expected that each attempt to patent a repurposed drug will have its own factspecific challenges.  Accordingly, the concepts discussed here are generalized and nonexhaustive.

The foundational inquiry for determining whether a repurposed drug can be patented in the United States is to consider whether, under 35 U.S.C. § 101, the drug constitutes patentable subject matter.  Section 101, in relevant part, provides: "[w]hoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor . . . ."[1]  Repurposed drugs are often non-nature-based compositions of matter (i.e., synthetic compounds that are not naturally occurring) that can be used in useful processes (e.g., methods of treating a disease by administering to a patient in need thereof a therapeutically effective dose of a drug).  Therefore, claims directed to repurposed drugs and methods of their use should not typically run afoul of § 101.  Even repurposed drugs that are nature-based compositions of matter may still be patentable, for example, if recited in a method of treatment claim.  Indeed, method of treatment claims reciting nature-based compositions of matter seem to be on more secure footing under § 101 in light of the recent decision in Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals,[2] at least because the United States Patent and Trademark Office has issued a recent memorandum to the Patent Examining Corps advising that the Patent Office intends to follow the legal reasoning in this case.[3]  Nevertheless, care must be taken when drafting claims to avoid § 101 issues.

Another significant hurdle to overcome with respect to patenting repurposed drugs is 35 U.S.C. § 102.  Section 102, as applied to a repurposed drug, requires that it was not previously patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before a patent application is filed to cover the repurposed drug.  In other words, a claim to the repurposed drug itself must be novel, in that it must recite something not previously publicly known.  Practically speaking, most composition of matter claims reciting only the repurposed drug will be excluded from patentability under § 102, because (almost by definition for a "repurposed" drug) the drug was previously known and thus its earlier public disclosure would be prior art to any subsequent patent filing.  Accordingly, composition claims directed to the repurposed drug itself will likely be anticipated because they are not reciting anything new.  Yet there are ways to overcome § 102 to obtain composition claims on repurposed drugs.

One useful approach for overcoming a § 102 rejection is to incorporate the repurposed drug into a composition that includes one or more other compounds to form a novel combination not previously known.  Importantly, the claimed combination can be any practical combination that is novel for purposes of overcoming § 102.  However, as discussed below, claims to pharmaceutical compositions that recite combinations with more than one key constituent (e.g., a therapeutically effective amount of a repurposed drug and a therapeutically effective amount of a second drug) are more likely to be patentable.  Additional details regarding specific amounts of drugs included in combinations or ratios between the drugs in the combination can add further grounds for finding such claims patentable over what was previously known in the prior art.

A further approach to obtaining claims directed to previously known drugs that are patentable in a § 102 context is to draft claims to novel pharmaceutical dosage forms.  Pharmaceutical dosage forms can be, for example, solids, liquids, delayed or extended release forms, and/or for a specific type of administration (e.g., oral, parenteral, intramuscular, etc.).  Many types of variations are possible with pharmaceutical dosage forms, which lend themselves to drafting novel claims.  For example, desired release characteristics and/or routes of administration may differ for the new use of the repurposed drug compared to its previous use, which would provide the basis of a novel claim.

As a final and particularly important example, a method claim reciting a repurposed drug may more easily overcome § 102 rejections.  Repurposing a drug for a new indication is typically a novel use of the drug.  Therefore, a method-of-use claim that recites a repurposed drug for treating a subject with the new indication should also be novel.  Such method claims are particularly useful because they are difficult for competitors to design around, and they are also available in many foreign jurisdictions (though with potentially different formats).

What is often more challenging for patenting a repurposed drug is overcoming an obviousness rejection.  Obviousness (or lack of inventive step) falls under 35 U.S.C. § 103, which states, in relevant part, that:

A patent for a claimed invention may not be obtained . . . , if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.[4]

Here, the basic calculus is that if a skilled artisan (e.g., a clinician or researcher in the same field of practice or study as the person seeking to repurpose a drug and with the average skill level of such clinicians or researchers) who understands the prior art would have reasonably expected the drug to be useful for the new indication, then a claim to a repurposed drug for the new indication may be obvious.  Obviousness rejections of claims to repurposed drugs can be very complex and can be based on a combination of several prior art references, each teaching one or more aspects of the rejected claims.

Unfortunately, the relatively straightforward strategies for overcoming a § 102 rejection are mostly ineffective for overcoming obviousness rejections.  Simple chemical combinations of repurposed drugs with other drugs that may make a novel composition are arguably obvious if they are nothing more than a routine exercise for a skilled pharmacologist.  Fortunately, there are ways to overcome obviousness rejections, but they can require planning well before filing a patent application, and indeed, experiments to investigate the usefulness of a repurposed drug should be designed with obviousness rejections in mind.  This is because one of the most powerful arguments against an obviousness rejection of claims directed to a repurposed drug is a showing of unexpected results.[5]  In this context, a showing of unexpected results can be a presentation of scientific data (often in the patent application, but data can also be presented after filing) that, for example, show a surprising effect of a drug that would not have been expected based on what was known at the time.  Examples of unexpected results can include that a drug surprisingly works as intended for a new indication, or that a drug works at the dose used (e.g., a surprisingly low dose), or that a combination of drugs demonstrates synergy when used together (their combined effect being greater than each drug acting alone), among others.[6]  Another powerful example of unexpected results is the discovery that the drug acts via a different target or has a different mechanism of action for the new use than for its previous use.  Such examples of unexpected results can overcome obviousness rejections for claims directed to method of use, or pharmaceutical dosage forms, or pharmaceutical compositions comprising a combination of drugs, respectively.  Therefore, care should be given to experimental design and the types of data that are collected in support of such evidence of non-obviousness.

Finally, a patent for a repurposed drug must satisfy 35 U.S.C. § 112, which requires that a patent application include:

[A] written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same.[7]

Section 112 also requires an application to have one or more claims "particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention."[8]  Basically, § 112 requires that, at the time of filing, the written description must enable a skilled artisan to replicate the invention (much like a scientific paper should enable a researcher to replicate the experiments and data presented in the paper) and that the claims must be fully supported by the written description.

Careful patent application planning and drafting can avoid or overcome § 112 rejections.  At a minimum, literal support for each claim should be provided, examples of various embodiments of the invention described (e.g., the repurposed drugs and indication, possible drug substitutions and/or derivatives, dosing amounts, dosage forms, excipients, dosing regimens, methods of treatment, etc.), and experimental data establishing drug effectiveness included.  The written description should also be drafted with sufficient detail and distinct variations of the invention to permit claim amendments that can dispose of a prior art rejection (under either § 102 or 103).  Indeed, all important details and variations of the invention envisioned must be included before filing because § 112 prohibits addition of "new matter" after filing.

In conclusion, patent protection is possible for previously known drugs being repurposed for new indications.  The best chances for patenting repurposed drugs occur when care is given to initial experimentation to establish the usefulness of the drugs and for identifying any unexpected properties of the drugs.  By combining robust invention disclosures with thoughtful and detailed application preparation, patent applications directed to repurposed drugs will be better prepared to successfully navigate the rigors of the Patent Office.

[1] 35 U.S.C. § 101.

[2] 887 F.3d 1117 (Fed. Cir. 2018).

[3] See Memorandum from Robert W. Bahr, Deputy Comm'r for Patent Examination Policy, to Patent Examining Corps (Jun. 7, 2018), available at https://www.uspto.gov/sites/default/files /documents/memo-vanda-20180607.PDF.

[4] 35 U.S.C. § 103.

[5] Other important objective evidence of non-obviousness, also known as "secondary considerations," includes evidence of commercial success, long-felt but unsolved needs, and failure of others.  See Graham v. John Deere Co. of Kansas City, 383 U.S. 1, 17 (1966).

[6] See Manual of Patent Examining Procedure §§ 716.02, 2145.

[7] 35 U.S.C. § 112(a).

[8] Id. § 112(b).

Comments

[Karl P. Dresdner, Jr. PhD, US Patent Agent 63,319]

John,

A very thoughtful and accurate pharma patenting presentation.
Thank you.

[Paul Cole]

May I echo these sentiments.

I remember hearing the question asked during UK litigation: which is more valuable for mankind - a new drug or a repurposed old drug? The answer, self-evidently is the repurposed drug since the way it is metabolized is known, as is its safety profile. Patients' bodies are not insulted by a wholly new substance but receive a familiar compound whose properties are known.

In Europe, as in the US, what is critical is evidence, gathered before filing and included in the specification. With appropriate evidence second medical use claims in Europe, as in the US, have a good chance of being held valid.

One thing that is needed is education of the medical and veterinary professions about the potential of patents for repurposed materials so that they are on the lookout for opportunities. Absent such education, papers will be published in the medical journals before patents are taken out and the opportunity for patent protection will be lost. Given the large investment in proving effectiveness in patient trials, the repurposed drug may never see the light of day.

[Anthony D. Sabatelli]

John,
This is a very well-written and thoughtful piece. I have circulated it around to my interns and some clients, because it presents so much basic information in an understandable manner.
Anthony

[dr shashikant kurani]

very useful for many repurposed drugs recently introduced in US market for orphan indications
Dr S.P.Kurani