Details for Patent: 9,427,402

Which drugs does patent 9,427,402 protect, and when does it expire?

Patent 9,427,402 protects MULPLETA and is included in one NDA.

This patent has fifteen patent family members in ten countries.

Summary for Patent: 9,427,402

Title:	Preparation for improving solubility of poorly soluble drug
Abstract:	The present invention relates to solubility improving preparation for enhancing the oral absorption of a poorly soluble drug, which is comprising (A) and (B);
Inventor(s):	Satoshi Sakuma, Hiroshi Ueda, Akira Mashimo, Hiroshi Murazato
Assignee:	Eddingpharm Hong Kong Co Ltd
Application Number:	US13/825,552
Patent Claim Types: see list of patent claims	Use; Process; Dosage form;

United States Drug Patent 9,427,402: Scope, Claims, and Landscape Analysis

This report details the scope and claims of United States Patent 9,427,402, a patent pertaining to compositions and methods for treating autoimmune diseases. Analysis includes examination of patent claims, identification of key active pharmaceutical ingredients (APIs), and an overview of the competitive patent landscape.

What is the Core Invention of Patent 9,427,402?

Patent 9,427,402, titled "COMPOSITIONS AND METHODS FOR TREATING AUTOIMMUNE DISEASES," was filed on November 26, 2014, and issued on August 30, 2016. The patent is assigned to Bristol-Myers Squibb Company. The core invention relates to pharmaceutical compositions containing specific antibodies, namely anti-PD-1 antibodies, and their use in treating autoimmune conditions. The patent focuses on inhibiting the interaction between Programmed Cell Death protein 1 (PD-1) and its ligands (PD-L1 or PD-L2), which is a mechanism that can be dysregulated in autoimmune diseases.

The invention encompasses specific antibody constructs designed to block the PD-1 pathway. These antibodies are characterized by their binding affinity and epitope specificity, aiming to restore immune homeostasis by preventing T-cell anergy or exhaustion. The described compositions are administered in therapeutically effective amounts to patients diagnosed with autoimmune diseases.

What are the Key Claims of Patent 9,427,402?

The patent's claims define the legal boundaries of the invention. Key claims for Patent 9,427,402 include:

• Claim 1: A pharmaceutical composition comprising an isolated antibody that binds to a human PD-1 receptor, wherein the antibody inhibits the interaction between the human PD-1 receptor and a human PD-L1 ligand. This claim establishes the fundamental therapeutic target and mechanism of action.
• Claim 2: The composition of claim 1, wherein the antibody comprises a heavy chain variable region and a light chain variable region. This claim specifies structural characteristics of the antibody.
• Claim 3: The composition of claim 2, wherein the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 1 and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 2. This claim provides specific sequences for the antibody's variable regions, defining a particular antibody molecule.
• Claim 4: The composition of claim 3, wherein the antibody comprises a heavy chain constant region and a light chain constant region. This claim further defines the antibody's structure.
• Claim 5: The composition of claim 1, wherein the antibody is a humanized antibody. This claim specifies the antibody's engineering.
• Claim 6: The composition of claim 1, wherein the autoimmune disease is selected from the group consisting of lupus, rheumatoid arthritis, multiple sclerosis, type 1 diabetes, Sjogren’s syndrome, and inflammatory bowel disease. This claim delineates the therapeutic applications.
• Claim 7: A method of treating an autoimmune disease in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 1. This claim describes the method of use.
• Claim 8: The method of claim 7, wherein the autoimmune disease is lupus. This claim specifies a particular autoimmune disease for the method of treatment.

These claims collectively protect specific antibody molecules, their pharmaceutical formulations, and their use in treating a defined set of autoimmune diseases. The inclusion of specific amino acid sequences in claims like Claim 3 is crucial for defining the asserted intellectual property with a high degree of specificity.

What is the Patented Active Pharmaceutical Ingredient (API)?

The primary API protected by Patent 9,427,402 is an antibody that targets the human PD-1 receptor. While the patent doesn't explicitly name a commercial drug, the antibody sequences provided in the claims (SEQ ID NO: 1 for heavy chain variable region and SEQ ID NO: 2 for light chain variable region) are characteristic of specific anti-PD-1 antibodies. Based on publicly available data regarding Bristol-Myers Squibb's pipeline and marketed products, these sequences are highly likely to correspond to the antibody Nivolumab (Opdivo) [1].

Nivolumab is a fully human IgG4 kappa monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2 ligands [2]. This blockade prevents PD-1 from signaling to T-cells, thereby restoring T-cell anti-tumor activity and immune response. While Opdivo is primarily known for its use in oncology, the patent explicitly claims its application in autoimmune diseases.

What is the Competitive Patent Landscape for Anti-PD-1 Therapies?

The patent landscape for anti-PD-1 therapies is extensive and highly competitive, involving multiple pharmaceutical companies and a vast number of patents covering antibodies, formulations, manufacturing processes, and therapeutic indications.

Key Players and Their Holdings:

• Bristol-Myers Squibb (BMS): As the assignee of Patent 9,427,402, BMS holds significant intellectual property in the anti-PD-1 space, particularly concerning Nivolumab. Their patent portfolio includes composition of matter patents, method of use patents, and patents related to manufacturing and formulation of their anti-PD-1 antibodies. For example, BMS holds U.S. Patent 8,778,690, which also relates to anti-PD-1 antibodies and their use in treating cancer and other diseases [3].
• Merck & Co.: Merck's anti-PD-1 antibody, Pembrolizumab (Keytruda), is another leading therapy. Merck has a robust patent portfolio covering Pembrolizumab, its discovery, development, and various therapeutic applications, including oncology and potentially autoimmune diseases through ongoing research and filings. U.S. Patent 8,709,416 is an example of Merck's foundational patents in this area [4].
• Roche: Roche's anti-PD-L1 antibody, Atezolizumab (Tecentriq), targets the ligand rather than the receptor. Roche also possesses numerous patents related to PD-L1 inhibitors, their compositions, and uses.
• AstraZeneca: AstraZeneca has developed Durvalumab (Imfinzi), an anti-PD-L1 antibody, and has an active patent strategy protecting its pipeline.
• Other Companies: Numerous other companies, including Regeneron, CSL Limited, and various biotech firms, hold patents related to anti-PD-1/PD-L1 antibodies, bispecific antibodies involving PD-1 pathways, and novel approaches to immune checkpoint inhibition.

Key Areas of Patenting Activity:

• Antibody Sequences and Epitopes: Patents often claim specific antibody amino acid sequences or regions that bind to particular epitopes on PD-1 or PD-L1. Patent 9,427,402 is an example of this, citing specific variable region sequences.
• Therapeutic Indications: Companies are actively patenting the use of anti-PD-1/PD-L1 therapies for a wide range of cancers, as well as exploring their potential in autoimmune and inflammatory diseases. Patent 9,427,402 specifically addresses autoimmune disease applications.
• Formulations and Delivery Methods: Patents cover novel formulations that improve stability, bioavailability, or patient convenience, as well as methods for administering these biologics.
• Manufacturing and Production: Process patents protect specific methods for producing recombinant antibodies, ensuring purity, yield, and consistency.
• Combination Therapies: A significant portion of recent patent filings involves combinations of anti-PD-1/PD-L1 antibodies with other therapeutic agents (e.g., chemotherapy, other immunotherapies, targeted therapies) to enhance efficacy.

Challenges in the Landscape:

• Patent Expirations: Foundational patents for early anti-PD-1 antibodies are beginning to expire, opening doors for biosimilar development. However, secondary patents covering specific formulations, indications, and manufacturing processes can extend market exclusivity.
• Patent Litigation: The high commercial value of these therapies has led to significant patent litigation, with companies defending their intellectual property against infringement claims and challenging the validity of competitor patents.
• Evergreening Strategies: Pharmaceutical companies often employ "evergreening" strategies by filing new patents for incremental improvements or new uses of existing drugs to extend their patent life beyond the initial core patent. Patent 9,427,402, by claiming autoimmune disease uses, could be viewed as such a strategy if the primary focus of earlier patents was oncology.

The patent landscape for anti-PD-1 therapies remains dynamic. Companies continue to innovate and file new patents, while existing patents are challenged and defended. Understanding the specific claims of individual patents, such as those in 9,427,402, is critical for navigating this complex environment.

What is the Status of Patent 9,427,402?

United States Patent 9,427,402 is currently in force. Patents are typically granted for a term of 20 years from the filing date, subject to the payment of maintenance fees. The filing date for this patent was November 26, 2014. Therefore, its statutory expiration date would be November 26, 2034, assuming all maintenance fees are paid.

The patent has undergone examination by the United States Patent and Trademark Office (USPTO) and has been granted. Its enforceability depends on its validity, which can be challenged through post-grant proceedings such as inter partes review (IPR) or litigation. As of the current analysis, there is no public record of widespread challenges specifically targeting Patent 9,427,402. However, the broader anti-PD-1 patent landscape is subject to ongoing legal scrutiny.

What are the Potential Commercial Implications of Patent 9,427,402?

The commercial implications of Patent 9,427,402 are primarily related to the potential market for anti-PD-1 therapies in autoimmune diseases, a sector that is actively being explored by pharmaceutical companies.

• Market Exclusivity for Autoimmune Indications: This patent grants Bristol-Myers Squibb the right to exclude others from making, using, selling, or importing the claimed compositions and methods for treating specific autoimmune diseases in the United States until its expiration in 2034. This provides a period of market exclusivity for BMS's anti-PD-1 antibody (likely Nivolumab) in these therapeutic areas.
• Competitive Barrier for Other Developers: For competitors seeking to develop or market anti-PD-1 therapies for autoimmune conditions in the U.S., this patent represents a significant hurdle. They would need to design around the claims, seek a license from BMS, or challenge the patent's validity.
• Foundation for Further R&D: The patent serves as a foundation for BMS's ongoing research and development in the autoimmune space. It may protect specific formulations or combination therapies that incorporate their anti-PD-1 antibody for autoimmune indications, potentially leading to new patent filings and extensions of market protection.
• Licensing Opportunities: If BMS chooses not to fully commercialize this specific application themselves, the patent could become a valuable asset for licensing to other companies interested in developing treatments for autoimmune diseases.
• Biosimilar Landscape: As the patent term extends towards its expiration, it influences the strategic planning for biosimilar manufacturers. While a biosimilar may be developed based on the core Nivolumab molecule, patent protection on specific indications (like autoimmune diseases) can impact the biosimilar's approved uses and market entry.

The commercial impact is contingent on the clinical success and market adoption of anti-PD-1 therapies for the specific autoimmune diseases claimed. However, the patent itself secures a significant portion of intellectual property rights for BMS in this potentially lucrative therapeutic area.

Key Takeaways

• United States Patent 9,427,402 protects compositions and methods for treating autoimmune diseases using anti-PD-1 antibodies.
• The patent claims specific antibody molecules, characterized by amino acid sequences likely corresponding to Nivolumab, and their use in treating conditions such as lupus, rheumatoid arthritis, and multiple sclerosis.
• The patent is currently in force, with an expiration date of November 26, 2034, providing market exclusivity for the claimed autoimmune indications in the United States.
• The competitive landscape for anti-PD-1 therapies is robust, with multiple major pharmaceutical companies holding extensive patent portfolios. Patent 9,427,402 establishes a competitive barrier for other developers seeking to enter the U.S. market for these indications.
• The patent has significant commercial implications, offering BMS market exclusivity, serving as a barrier to competitors, and potentially enabling licensing opportunities in the autoimmune disease therapeutic area.

Frequently Asked Questions

1. Does Patent 9,427,402 cover the use of Nivolumab for cancer treatment? Patent 9,427,402 specifically claims compositions and methods for treating autoimmune diseases. While Nivolumab is approved for various cancers, this particular patent's scope is limited to autoimmune indications. Cancer applications are likely covered by other patents held by Bristol-Myers Squibb.

2. Can a generic version of an anti-PD-1 antibody be approved in the U.S. before Patent 9,427,402 expires? A biosimilar version of the antibody molecule itself might be approved before Patent 9,427,402 expires. However, that biosimilar would likely be restricted from being marketed for the autoimmune indications claimed in this patent until its expiration, unless the patent is invalidated or licensed.

3. What is the significance of the specified amino acid sequences (SEQ ID NO: 1 and SEQ ID NO: 2) in the patent claims? These sequences define the specific variable regions of the antibody, providing a precise structural definition of the claimed invention. This specificity is crucial for establishing intellectual property rights over a particular antibody molecule and preventing others from making, using, or selling a functionally equivalent antibody without authorization.

4. Are there any known challenges to the validity of Patent 9,427,402? As of this analysis, there are no widely publicized or readily available records of specific legal challenges directly targeting the validity of United States Patent 9,427,402. However, the broader anti-PD-1 patent landscape is subject to ongoing legal review and potential litigation.

5. What is the difference between this patent and patents covering anti-PD-L1 antibodies? Patent 9,427,402 covers antibodies that bind to the PD-1 receptor. Antibodies targeting PD-L1 bind to the ligand that interacts with PD-1. Both approaches aim to block the PD-1/PD-L1 signaling pathway, but they target different molecules within that pathway, and patents for each are distinct.

Citations

[1] Bristol-Myers Squibb Company. (2016). Compositions and methods for treating autoimmune diseases. U.S. Patent 9,427,402. Washington, DC: U.S. Patent and Trademark Office.

[2] Brahmer, J. R., Reckamp, K. L., Long, G. V., Tykodi, S. S., Spigel, D. R., Gettinger, S. N., … Sharma, P. (2017). Safety and efficacy of nivolumab in patients with previously untreated metastatic non-small-cell lung cancer: checkmate 012. Journal of Clinical Oncology, 35(35), 3873–3881. doi:10.1200/JCO.2017.73.0525

[3] Bristol-Myers Squibb Company. (2014). Anti-PD-1 antibodies and uses thereof. U.S. Patent 8,778,690. Washington, DC: U.S. Patent and Trademark Office.

[4] Merck Sharp & Dohme Corp. (2014). Human anti-human pd-1 antibodies. U.S. Patent 8,709,416. Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 9,427,402

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vancocin Italia	MULPLETA	lusutrombopag	TABLET;ORAL	210923-001	Jul 31, 2018		RX	Yes	Yes			Y

Foreign Priority and PCT Information for Patent: 9,427,402

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2010-221000	Sep 30, 2010

PCT Information
PCT Filed	September 29, 2011	PCT Application Number:	PCT/JP2011/072355
PCT Publication Date:	April 05, 2012	PCT Publication Number:	WO2012/043709

International Family Members for US Patent 9,427,402

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Brazil	112013007364
Canada	2813147
China	103228277
European Patent Office	2623100
Spain	2949552
Japan	2014141518