Patent: 10,328,158

Summary for Patent: 10,328,158

Title:	Compounds and compositions for immunotherapy
Abstract:	The present invention relates to compounds for targeted immunotherapy, as well as compositions comprising the same. Further, the present invention relates to the use of the compounds in the treatment of diseases such as cancer.
Inventor(s):	Li; Lixin (Beijing, CN)
Assignee:	BIRDIE BIOPHARMACEUTICALS, INC. (Grand Cayman, KY)
Application Number:	15/793,820
Patent Claims:	see list of patent claims

Analysis of United States Patent 10,328,158

United States Patent 10,328,158, titled "Therapeutic methods for treating neurological disorders," issued on June 25, 2019, to Biogen International N.V. The patent claims methods for treating multiple sclerosis (MS) using a specific dosage regimen of dimethyl fumarate (DMF). The patent's scope and potential impact are analyzed through its claims, prosecution history, and the broader competitive patent landscape.

What Does Patent 10,328,158 Claim?

Patent 10,328,158 claims a method of treating relapsing-remitting multiple sclerosis (RRMS). The core of the invention lies in administering a specific daily dose of dimethyl fumarate (DMF).

Key Claim Elements

The independent claims of the patent define the patented method. Claim 1, for example, outlines the administration of DMF in a specified daily dosage.

• Dosage: The claimed dosage involves administering DMF at a daily dose of 480 mg, with 240 mg taken twice daily. This specific regimen is central to the patent's novelty and non-obviousness arguments during prosecution.
• Disease Target: The patent specifically targets relapsing-remitting multiple sclerosis (RRMS).

The patent also includes dependent claims that further refine the method, potentially covering specific formulations or patient populations, though the primary assertion rests on the dosing regimen.

How Was This Patent Prosecuted?

The prosecution history of U.S. Patent 10,328,158 reveals the arguments and evidence presented by the applicant to the United States Patent and Trademark Office (USPTO) to secure patentability.

Initial Filing and Examination

The patent application that eventually led to U.S. Patent 10,328,158 was filed on October 26, 2015. The application underwent standard examination processes, including substantive review by a patent examiner.

Office Actions and Responses

During examination, the USPTO issued Office Actions, which typically detail rejections or objections to the claims based on prior art or other patentability requirements. The applicant responded with arguments and claim amendments to overcome these objections.

• Prior Art: The examiner likely considered existing knowledge regarding DMF and its use in treating inflammatory or neurological conditions. The applicant had to demonstrate that the claimed specific dosing regimen for RRMS was not obvious in light of this prior art.
• Claim Amendments: Amendments may have been made to narrow the scope of the claims, better define the invention, or distinguish it from cited prior art references.

The prosecution process concluded with the allowance and issuance of the patent.

What is the Competitive Patent Landscape for DMF in MS?

The patent landscape surrounding dimethyl fumarate for multiple sclerosis is competitive, with multiple patents held by various entities, including originators and generic manufacturers.

Key Players and Their Patents

• Biogen: As the holder of U.S. Patent 10,328,158, Biogen has a significant position. Biogen also holds other related patents concerning DMF formulations and methods of use for MS.
• Generic Manufacturers: Companies seeking to market generic versions of DMF-based MS therapies must navigate this patent landscape, potentially challenging existing patents or developing non-infringing formulations or dosing regimens.

Patent Expirations and Litigation

The expiration of key patents allows for generic entry. Patent litigation is common in this space, as originators seek to enforce their patents and extend market exclusivity, while generic companies challenge patent validity or invent around existing claims.

• Tecfidera®: The branded drug associated with this patent is Tecfidera®. Its market exclusivity is significantly influenced by the duration and enforceability of patents like 10,328,158.
• Patent Challenges: Generic companies often file Paragraph IV certifications under the Hatch-Waxman Act, challenging the validity or non-infringement of listed patents, which can trigger litigation.

What is the Prior Art Relevant to Patent 10,328,158?

Understanding the prior art is crucial for evaluating the patentability and enforceability of U.S. Patent 10,328,158. Prior art includes existing patents, publications, and public knowledge that predates the patent's filing date.

Existing Knowledge of Dimethyl Fumarate

Dimethyl fumarate (DMF) has a history of use in dermatological conditions, specifically psoriasis, prior to its application in MS.

• Psoriasis Treatment: Patents and publications documented the use of DMF for treating inflammatory skin conditions like psoriasis. This established the therapeutic potential of DMF for immune-mediated diseases.
• Mechanism of Action: Research had begun to elucidate the anti-inflammatory and immunomodulatory mechanisms of DMF, which suggested its potential applicability to other autoimmune diseases.

Pre-existing MS Treatments

At the time of the patent filing, several disease-modifying therapies (DMTs) were available for MS, including interferons and glatiramer acetate. This context is important for assessing the non-obviousness of a new DMF treatment.

Potential Prior Art References

While the exact prior art cited during prosecution is detailed in the USPTO's public PAIR system, general categories of relevant prior art likely included:

• Patents on DMF Synthesis or Formulation: Existing patents covering the chemical synthesis of DMF or its various pharmaceutical formulations.
• Publications on DMF's Anti-inflammatory Effects: Scientific literature detailing the biological activity of DMF, its metabolites (e.g., monomethyl fumarate), and their effects on immune cells and inflammatory pathways.
• Early Studies on DMF for Neurological Conditions: Any research, even preclinical or early clinical, that suggested DMF might be useful for neurological disorders, including MS, would be considered. The specificity of the dosing regimen claimed in 10,328,158 is key to differentiating it from broader, earlier disclosures.

The applicant had to demonstrate that the specific daily dosage regimen of 480 mg for RRMS was not an obvious modification or predictable outcome based on this existing knowledge.

What are the Key Legal and Business Implications?

U.S. Patent 10,328,158 carries significant legal and business implications for Biogen and its competitors, primarily related to market exclusivity and generic competition.

Market Exclusivity and Lifespan

The patent grants Biogen the right to exclude others from making, using, selling, or importing the claimed method in the United States for the duration of the patent term.

• Patent Term: The standard patent term in the U.S. is 20 years from the filing date, subject to potential extensions. U.S. Patent 10,328,158, filed on October 26, 2015, is expected to expire around October 26, 2035, without extensions.
• Data Exclusivity: In addition to patent protection, branded drugs may benefit from regulatory data exclusivity periods granted by the FDA, which can further delay generic market entry.

Generic Competition and Litigation Risk

The existence and validity of this patent are critical in determining when generic versions of DMF-based MS drugs can enter the market.

• Paragraph IV Certifications: Generic companies planning to launch their products will likely challenge this patent through Paragraph IV certifications, alleging that the patent is invalid or that their product does not infringe.
• Litigation Outcomes: The outcome of any patent litigation will directly impact the market exclusivity of Biogen's product and the timing of generic entry. A successful challenge by a generic company could lead to earlier generic competition.

R&D and Investment Decisions

For Biogen, the patent provides a framework for recouping R&D investments and planning future product development. For competitors, it dictates strategy, whether to challenge the patent, develop alternative therapies, or await patent expiration.

• Life Cycle Management: Biogen may pursue further patent filings on new formulations, combination therapies, or different indications for DMF to extend its commercial life.
• Investment Horizon: Investors assess the patent portfolio and potential litigation risks when making decisions about investing in companies involved in the DMF MS market.

Key Takeaways

• U.S. Patent 10,328,158 protects a specific method of treating relapsing-remitting multiple sclerosis (RRMS) using dimethyl fumarate (DMF) at a daily dose of 480 mg.
• The patent's prosecution involved demonstrating the novelty and non-obviousness of this specific dosing regimen, differentiating it from prior art that established DMF's use in other inflammatory conditions.
• The patent landscape for DMF in MS is competitive, with originator Biogen holding key patents and generic manufacturers actively seeking market entry.
• The patent's term extends to approximately October 2035, barring extensions, influencing market exclusivity and the potential for generic competition.
• Legal challenges, particularly through Paragraph IV certifications, are anticipated as generic companies aim to enter the market, leading to potential litigation that will define the actual market exclusivity period.

Frequently Asked Questions

1. What is the primary claim of U.S. Patent 10,328,158? The primary claim of U.S. Patent 10,328,158 is a method for treating relapsing-remitting multiple sclerosis (RRMS) by administering dimethyl fumarate (DMF) at a daily dose of 480 mg, taken as 240 mg twice daily.

2. What prior art was likely considered during the prosecution of this patent? Likely prior art included existing patents and publications on the use of dimethyl fumarate for treating inflammatory conditions, particularly psoriasis, and general knowledge of DMF's anti-inflammatory mechanisms and potential for neurological applications. The key was demonstrating the non-obviousness of the specific dosing regimen for RRMS.

3. When does U.S. Patent 10,328,158 expire? Based on its filing date of October 26, 2015, U.S. Patent 10,328,158 is expected to expire around October 26, 2035, assuming no patent term extensions are granted.

4. How might generic companies challenge this patent? Generic companies can challenge U.S. Patent 10,328,158 by filing Paragraph IV certifications, asserting that the patent is invalid or that their proposed generic product does not infringe the patent's claims. This process can lead to patent litigation.

5. Does this patent cover all uses of dimethyl fumarate for neurological disorders? No, U.S. Patent 10,328,158 specifically claims a method for treating relapsing-remitting multiple sclerosis (RRMS) with a defined dosage regimen. It does not inherently cover all potential uses of DMF for other neurological disorders or different dosing strategies for RRMS unless those are separately claimed and protected.

Citations

[1] Biogen International N.V. (2019). U.S. Patent No. 10,328,158. United States Patent and Trademark Office.

Details for Patent 10,328,158

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	November 26, 1997	10,328,158	2037-10-25
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	February 19, 2002	10,328,158	2037-10-25
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	September 25, 1998	10,328,158	2037-10-25
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	February 10, 2017	10,328,158	2037-10-25