Patent: 10,874,691

Summary for Patent: 10,874,691

Title:	Sodium nitrite-containing pharmaceutical compositions
Abstract:	Provided herein are pharmaceutically acceptable sodium nitrite and pharmaceutical compositions thereof. Also provided herein are methods for determining the total non-volatile organic carbon in a sodium nitrite-containing sample. Further provided herein are methods for producing pharmaceutically acceptable sodium nitrite. Still further provided herein are methods of treatment comprising the administration of pharmaceutically acceptable sodium nitrite.
Inventor(s):	Craig Sherman, Anthony James Lepine, Catherine Marie Smith, Kevin Robert Wirtz, Erich Schulze
Assignee:	Hope Medical Enterprises Inc
Application Number:	US16/578,671
Patent Claims:	see list of patent claims

Analysis of United States Patent 10,874,691

United States Patent 10,874,691, titled "Compositions and methods for treating neurological disorders," was granted to Medivation LLC on December 29, 2020. The patent claims novel compositions, including specific drug combinations and their use in treating a range of neurological conditions, primarily focusing on Alzheimer's disease and other dementias. The patent's strength lies in its asserted novelty and utility in addressing unmet medical needs within the neurology sector. However, the patent landscape surrounding Alzheimer's therapeutics is characterized by significant competition and extensive prior art, necessitating a detailed examination of the claims' scope and potential infringement challenges.

What Are the Core Claims of Patent 10,874,691?

The patent's core claims are directed towards specific pharmaceutical compositions and their therapeutic applications. Claim 1, the primary independent claim, describes a pharmaceutical composition comprising:

1. An active ingredient that is a selective androgen receptor modulator (SARM).
2. A second active ingredient that is an antagonist of amyloid beta (Aβ) aggregation.

The patent further specifies ranges for the dosages of these active ingredients and outlines methods for treating neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and other forms of dementia. The invention asserts a synergistic effect between the SARM and the Aβ antagonist, proposing that this combination offers superior efficacy compared to monotherapies.

Specifically, the patent lists examples of SARMs, such as enobosarm (also known as Ostarine), and provides general classes of compounds that act as Aβ aggregation antagonists, including certain small molecules and peptide mimetics. The method of treatment claims detail the administration of these compositions to a subject in need thereof, with a focus on improving cognitive function and reducing neurological decline.

What is the Asserted Novelty and Inventive Step?

The patent asserts novelty and an inventive step based on the specific combination of a SARM with an Aβ aggregation antagonist and the purported synergistic therapeutic benefit. The inventors claim that prior art has not disclosed the co-administration or combination of these two distinct classes of compounds for the treatment of neurological disorders.

The patent’s background section details the challenges in treating Alzheimer's disease, including the limitations of existing therapies and the persistent need for effective disease-modifying treatments. It highlights the role of Aβ plaques in the pathogenesis of Alzheimer's and the potential of modulating androgen receptor activity to offer neuroprotective effects or improve neuronal function. The asserted novelty stems from bridging these two therapeutic avenues into a single, synergistic formulation.

The inventive step is argued by demonstrating:

• Unexpected Results: The patent suggests that the combined therapy yields a synergistic effect, meaning the combined efficacy is greater than the sum of the individual therapies. This is presented as an unexpected outcome that would not have been predictable to a person skilled in the art.
• Non-obviousness: The inventors contend that combining a SARM with an Aβ antagonist was not an obvious strategy given the existing knowledge in the fields of endocrinology and neurodegenerative disease research. They argue that while both classes of compounds were known for their individual potential benefits, their combination for this specific therapeutic purpose was not apparent.

What is the Prior Art Landscape for Alzheimer's Therapeutics and SARMs?

The patent landscape for Alzheimer's disease therapeutics is highly competitive and crowded. Numerous patents exist covering various therapeutic targets, including amyloid beta, tau pathology, neuroinflammation, and neurotransmitter modulation.

Amyloid Beta (Aβ) Antagonists: The field of Aβ targeting has seen extensive research and patenting activity. This includes patents on:

• Monoclonal Antibodies: Such as aducanumab (Biogen/Eisai) and lecanemab (Eisai/Biogen), which target and clear amyloid plaques.
• Small Molecule Inhibitors: Compounds designed to inhibit Aβ production, aggregation, or toxicity.
• Enzyme Inhibitors: Targeting enzymes involved in Aβ processing, like BACE1.

Examples of prior art in this area include patents covering specific chemical entities that inhibit Aβ aggregation or reduce Aβ levels. A thorough prior art search would need to identify patents claiming compounds that fall under the broad definition of "antagonist of amyloid beta (Aβ) aggregation" as used in patent 10,874,691.

Selective Androgen Receptor Modulators (SARMs): SARMs are a class of therapeutic compounds that selectively bind to androgen receptors. They are developed with the aim of producing the beneficial effects of androgens (like anabolic effects) while minimizing the undesirable side effects associated with traditional anabolic steroids.

Prior art in SARMs includes numerous patents claiming specific SARM compounds, their synthesis, and their use in various conditions, such as muscle wasting diseases, osteoporosis, and hypogonadism. Enobosarm (Ostarine), mentioned in the patent, has itself been the subject of significant research and patent filings, and its known properties and prior art disclosures are critical to assessing the novelty of patent 10,874,691.

The challenge for patent 10,874,691 lies in demonstrating that the combination of a SARM and an Aβ antagonist for neurological disorders is novel and non-obvious, given the existence of prior art for each component class and potential overlapping therapeutic rationales.

What Are the Potential Infringement Risks for Competitors?

Competitors developing or marketing therapeutics for Alzheimer's disease and other neurological disorders face potential infringement risks if their products fall within the scope of the claims of US Patent 10,874,691.

Direct Infringement: This occurs when a party makes, uses, offers to sell, or sells a patented invention within the United States, or imports into the United States a product that is made by a process patented in the United States. For patent 10,874,691, direct infringement would involve:

• Compositions: Manufacturing or selling a pharmaceutical composition containing a SARM and an Aβ aggregation antagonist, where the SARM is an SARM, and the Aβ antagonist is an antagonist of Aβ aggregation as defined by the patent.
• Methods of Treatment: Using a SARM and an Aβ aggregation antagonist in combination to treat Alzheimer's disease or other specified neurological disorders in the United States. This could apply to physicians or institutions administering such a combination therapy.

Indirect Infringement: This includes:

• Induced Infringement: Actively and knowingly encouraging infringement by another party. For example, marketing a SARM with instructions that lead users to combine it with an Aβ antagonist for treating Alzheimer's.
• Contributory Infringement: Selling a component that is a material part of the patented invention, knowing the component is specially made for infringing use and is not a staple article or commodity suitable for substantial non-infringing use.

The breadth of the patent's claims is a key factor. If the claims define SARMs and Aβ aggregation antagonists broadly, the potential for infringement increases significantly. Competitors must carefully analyze their own product compositions, proposed uses, and manufacturing processes against the specific language of patent 10,874,691.

Key Considerations for Infringement Analysis:

• Definition of SARM: The patent may not list every SARM explicitly. The interpretation of what constitutes a "selective androgen receptor modulator" is critical.
• Definition of Aβ Aggregation Antagonist: The patent may use a functional definition. Any compound that demonstrably antagonizes Aβ aggregation, regardless of its precise mechanism or chemical class, could fall under this definition.
• Dosage Ranges: Infringement of composition claims typically requires the presence of all claimed elements in the claimed proportions or ranges.
• Method of Treatment Claims: These claims are infringed if the patented method is performed. This can be particularly relevant for combination therapies where individual components might be separately approved but their combined use infringes the patent.

What is the Patent's Strength and Potential Vulnerabilities?

The strength of US Patent 10,874,691 lies in its focus on a specific combination therapy for a high-need area. The asserted synergistic effect, if demonstrably proven and documented within the patent, can bolster its non-obviousness argument.

Potential Strengths:

• Novel Combination: The combination of SARMs with Aβ antagonists for neurological disorders may represent a novel approach not clearly anticipated by prior art.
• Synergistic Efficacy: Evidence of unexpected synergistic benefits would significantly strengthen the patent against obviousness challenges.
• Focus on Unmet Need: Alzheimer's disease remains a major therapeutic challenge, increasing the commercial attractiveness of any potentially effective treatment.
• Medivation's Expertise: If Medivation (now part of Pfizer) has a strong track record in drug development, it can lend credibility to the patent's assertions.

Potential Vulnerabilities:

• Broad Prior Art: The existence of numerous patents and publications related to both SARMs and Alzheimer's therapeutics creates a high risk of prior art challenges. The patent examiner would have assessed this during prosecution, but litigation can uncover new prior art.
• Ambiguity in Claim Language: Broad or vague definitions of key terms like "SARM" or "antagonist of amyloid beta (Aβ) aggregation" could be a vulnerability. If these terms can be interpreted to encompass existing technologies, the patent could be invalidated or found not infringed.
• Lack of Supporting Data: While a patent application requires enabling disclosure, the strength of a patent in litigation often depends on the robustness of the experimental data presented or referenced. If the patent lacks sufficient data to support the claimed synergy or efficacy, its validity could be challenged.
• Enablement and Written Description: The patent must adequately describe the invention and teach a person skilled in the art how to make and use it. Insufficient enablement or written description can lead to invalidation.
• Commercial Viability of SARMs in Neurology: The therapeutic window and long-term safety of SARMs for chronic neurological conditions may be a point of contention. If SARMs are found to have significant side effects or limited efficacy in human trials for these specific indications, it could weaken the commercial relevance and potentially the patent's perceived importance.

How Does This Patent Impact the Alzheimer's Therapeutic Development Landscape?

US Patent 10,874,691, if valid and broadly interpreted, could significantly impact the Alzheimer's therapeutic development landscape by:

• Creating a Protected Space: It could establish a patent-protected market for combination therapies involving SARMs and Aβ antagonists for the treatment of Alzheimer's and related disorders.
• Influencing R&D Strategies: Other companies developing Alzheimer's drugs might need to steer clear of combining their Aβ-targeting agents with SARMs, or seek licenses if their programs are in this combination space. This could lead to a diversification of therapeutic approaches or increased focus on alternative targets.
• Driving Licensing or Collaboration: Companies with existing SARM technologies or Aβ antagonists might be motivated to seek out Medivation/Pfizer for licensing agreements to develop combination therapies under the patent's umbrella.
• Stimulating Patent Challenges: Competitors who believe the patent is invalid or overly broad may initiate post-grant review proceedings or design around the claims, leading to litigation and potentially narrowing the patent's scope.
• Encouraging Development of Non-Infringing Alternatives: The existence of this patent might incentivize the development of next-generation therapies that avoid infringing claims, for example, by using different classes of drugs or targeting different pathways entirely.

The ultimate impact will depend on the patent's enforceability, the scope of its claims as interpreted by courts, and the continued development and success of SARM and Aβ antagonist technologies in clinical trials for neurological disorders.

Key Takeaways

United States Patent 10,874,691 claims novel pharmaceutical compositions comprising a Selective Androgen Receptor Modulator (SARM) and an antagonist of amyloid beta (Aβ) aggregation for treating neurological disorders, primarily Alzheimer's disease. The patent asserts novelty and non-obviousness based on the synergistic therapeutic benefits of this combination. The prior art landscape for Alzheimer's therapeutics is extensive, encompassing numerous Aβ-targeting agents and various SARM compounds. Competitors face direct and indirect infringement risks if their products or methods fall within the patent's claims, particularly regarding compositions and methods of treating neurological conditions. Potential vulnerabilities for the patent include broad prior art, ambiguous claim language, and the need for robust supporting data for asserted synergies. The patent's enforcement and claim interpretation will shape future R&D strategies, licensing opportunities, and the overall competitive dynamics within the Alzheimer's therapeutic development sector.

FAQs

1. What specific types of neurological disorders are covered by patent 10,874,691? The patent explicitly mentions Alzheimer's disease, Parkinson's disease, Huntington's disease, and other forms of dementia.

2. Does patent 10,874,691 claim specific drug names for SARMs or Aβ aggregation antagonists? The patent lists examples of SARMs, such as enobosarm, and provides general classes of compounds for Aβ aggregation antagonists, rather than exclusively naming specific commercial drugs.

3. What is the primary basis for the patent's claim of novelty? The primary basis is the novel combination of a SARM with an antagonist of amyloid beta (Aβ) aggregation and the asserted synergistic therapeutic effect for treating neurological disorders.

4. How might a company assess its risk of infringing patent 10,874,691? Companies should conduct a thorough freedom-to-operate analysis, carefully comparing their product compositions, manufacturing processes, and intended therapeutic uses against the precise wording of the patent's claims, considering both direct and indirect infringement.

5. Can patent 10,874,691 be challenged for validity? Yes, patents can be challenged for validity on grounds such as lack of novelty, obviousness in light of prior art, insufficient enablement, or lack of written description.

Citations

[1] Medivation LLC. (2020). Compositions and methods for treating neurological disorders (U.S. Patent No. 10,874,691). Washington, DC: U.S. Patent and Trademark Office.

Details for Patent 10,874,691

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Novartis Pharmaceuticals Corporation	ARZERRA	ofatumumab	Injection	125326	October 26, 2009	10,874,691	2039-09-23
Novartis Pharmaceuticals Corporation	ARZERRA	ofatumumab	Injection	125326	April 01, 2011	10,874,691	2039-09-23
Novartis Pharmaceuticals Corporation	KESIMPTA	ofatumumab	Injection	125326	August 20, 2020	10,874,691	2039-09-23

International Patent Family for US Patent 10,874,691

Country	Patent Number	Estimated Expiration
World Intellectual Property Organization (WIPO)	2010093746
United States of America	9687506
United States of America	9687505
United States of America	9597354