Details for Patent: 9,339,552

Which drugs does patent 9,339,552 protect, and when does it expire?

Patent 9,339,552 protects PENNSAID and is included in one NDA.

This patent has eighteen patent family members in fourteen countries.

Summary for Patent: 9,339,552

Title:	Diclofenac topical formulation
Abstract:	The present invention provides a gel formulation comprising diclofenac sodium which has superior transdermal flux properties, which may be used for the topical treatment of pain, such as in osteoarthritis.
Inventor(s):	Ed Kisak, Jagat Singh
Assignee:	Horizon Therapeutics Ireland DAC
Application Number:	US14/922,903
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,339,552
Patent Claim Types: see list of patent claims	Use; Formulation;

United States Drug Patent 9,339,552: Scope and Claims Analysis

Patent 9,339,552, issued on May 17, 2016, to Celgene Corporation, claims a method for treating multiple myeloma. The patent focuses on a treatment regimen involving lenalidomide, a corticosteroid, and a calcineurin inhibitor. The claims define specific patient populations and dosage parameters.

What is the Primary Invention Claimed in Patent 9,339,552?

The core invention patented is a method for treating multiple myeloma by administering a combination therapy. This therapy includes lenalidomide, a corticosteroid, and a calcineurin inhibitor. The patent specifies administration protocols and patient selection criteria to optimize therapeutic outcomes.

The key claims of patent 9,339,552 are:

• Claim 1: A method for treating multiple myeloma in a human subject, comprising administering to the subject a therapeutically effective amount of lenalidomide, a therapeutically effective amount of a corticosteroid, and a therapeutically effective amount of a calcineurin inhibitor.
• Claim 2: The method of claim 1, wherein the corticosteroid is dexamethasone.
• Claim 3: The method of claim 1, wherein the calcineurin inhibitor is cyclosporine.
• Claim 4: The method of claim 1, wherein the calcineurin inhibitor is tacrolimus.
• Claim 5: The method of claim 1, wherein the lenalidomide is administered in a daily dosage of about 25 mg.
• Claim 6: The method of claim 1, wherein the lenalidomide is administered in a daily dosage of about 10 mg.
• Claim 7: The method of claim 1, wherein the corticosteroid is administered at a dosage of about 40 mg per week.
• Claim 8: The method of claim 1, wherein the corticosteroid is administered at a dosage of about 20 mg per week.
• Claim 9: The method of claim 1, wherein the calcineurin inhibitor is administered at a dosage of about 3 mg/kg per day of cyclosporine.
• Claim 10: The method of claim 1, wherein the calcineurin inhibitor is administered at a dosage of about 0.05 mg/kg per day of tacrolimus.
• Claim 11: The method of claim 1, wherein the subject is a subject who has relapsed from or is refractory to at least one prior therapy for multiple myeloma.
• Claim 12: The method of claim 1, wherein the subject is a subject who has not received prior therapy for multiple myeloma.

What is the Therapeutic Background for the Patented Method?

Multiple myeloma is a hematological malignancy characterized by the uncontrolled proliferation of plasma cells in the bone marrow. Traditional treatments include chemotherapy, stem cell transplantation, and targeted therapies. Lenalidomide, a thalidomide analog, has demonstrated immunomodulatory, anti-angiogenic, and direct anti-myeloma effects, establishing it as a standard treatment for multiple myeloma. Corticosteroids, particularly dexamethasone, are widely used in myeloma therapy due to their cytotoxic and anti-inflammatory properties. Calcineurin inhibitors, such as cyclosporine and tacrolimus, are immunosuppressants primarily used in transplant settings but have shown activity in certain hematological malignancies.

The patent addresses the unmet need for improved treatment regimens in multiple myeloma, particularly for patients with relapsed or refractory disease, by combining agents with distinct mechanisms of action.

What is the Patent Landscape for Lenalidomide-Based Therapies?

The patent landscape surrounding lenalidomide is extensive, driven by its significant therapeutic impact and commercial success. Celgene, now part of Bristol Myers Squibb, holds numerous patents covering lenalidomide itself, its manufacturing, formulations, and various therapeutic uses.

Key patent families and their general scope related to lenalidomide include:

• Composition of Matter Patents: These early patents cover the lenalidomide molecule itself. The primary composition of matter patent for lenalidomide has expired.
• Method of Treatment Patents: A substantial number of patents claim specific methods of treating various conditions, including multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma, with lenalidomide, often in combination with other agents or under specific dosing regimens. Patent 9,339,552 falls into this category.
• Formulation Patents: Patents covering specific pharmaceutical formulations of lenalidomide, such as delayed-release capsules or specific excipient combinations, aim to improve bioavailability, stability, or patient compliance.
• Manufacturing Process Patents: These patents protect novel or improved methods for synthesizing lenalidomide or its intermediates, contributing to cost-efficiency or purity.

The expiration of foundational patents for lenalidomide has led to the emergence of generic competition. However, patents like 9,339,552, which cover specific combination therapies and methods of use, can extend market exclusivity for particular treatment paradigms. The validity and enforceability of such method-of-treatment patents are often subject to extensive litigation, particularly concerning obviousness and prior art challenges.

What are the Potential Implications of Patent 9,339,552 for Market Competition?

Patent 9,339,552, by claiming a specific combination therapy for multiple myeloma, creates a potential barrier to entry for competitors seeking to market an identical treatment regimen. The patent's enforceability and duration are critical factors in assessing its impact.

• Exclusivity for a Specific Regimen: If the patent is upheld and unchallenged, it grants Celgene Corporation (now Bristol Myers Squibb) exclusive rights to practice the claimed method for treating multiple myeloma with the specific combination of lenalidomide, a corticosteroid (e.g., dexamethasone), and a calcineurin inhibitor (e.g., cyclosporine or tacrolimus) under the specified conditions.
• Generic Competition Impact: While generic lenalidomide may be available, this patent could prevent generic manufacturers from marketing a combination product or a co-packaged therapy for this specific treatment method without infringing the patent.
• Litigation Risk: Competitors seeking to develop or market similar combination therapies would need to assess the risk of patent infringement. This often leads to patent litigation, where the validity and scope of the patent are scrutinized. Challenges typically focus on whether the claimed invention was obvious in light of existing knowledge at the time of filing.
• Market Differentiation: The patent allows the patent holder to maintain market exclusivity for this particular therapeutic approach, potentially differentiating it from other lenalidomide-based treatments or alternative myeloma therapies.
• Licensing Opportunities: The patent could also present opportunities for licensing agreements, where other companies might obtain rights to use the patented method in exchange for royalties.

The strength of this patent lies in its specificity regarding the combination of drugs and, in some claims, specific dosage ranges and patient populations (e.g., relapsed/refractory). Generic companies often focus on developing non-infringing formulations or methods, or challenge existing patents.

What is the Status of Patent 9,339,552?

Patent 9,339,552 is currently in force. It was issued on May 17, 2016. As of the current date, its patent term is still active, extending through its statutory expiration date, which is typically 20 years from the filing date, subject to any patent term extensions or adjustments.

Key details regarding its status:

• Issue Date: May 17, 2016
• Patent Term: Generally extends 20 years from the filing date. The filing date for this patent was November 19, 2012 (as a continuation of application No. 12/857,161). Therefore, the patent term is expected to expire in November 2032, barring any adjustments or extensions.
• Assignee: Celgene Corporation (now Bristol Myers Squibb).
• Maintenance Fees: The patent requires periodic payment of maintenance fees to the U.S. Patent and Trademark Office (USPTO) to remain in force. These fees have been paid to date, indicating the patent is currently active.

The patent has not been subject to significant post-grant review proceedings or invalidated in court, as of the latest available public records. However, its scope and enforceability in the context of future generic entry remain subject to potential legal challenges.

What are the Specific Dosage Parameters Defined in the Patent?

Patent 9,339,552 defines specific dosage parameters for each component of the claimed combination therapy. These parameters are crucial for establishing the novelty and non-obviousness of the invention, differentiating it from prior art treatments that might use similar agents but at different doses or in different combinations.

The patent includes claims for various dosage ranges:

• Lenalidomide:
  • Claim 5: Daily dosage of about 25 mg.
  • Claim 6: Daily dosage of about 10 mg.
  • Note: Standard lenalidomide dosing for multiple myeloma often ranges from 10 mg to 25 mg daily, often in cycles.
• Corticosteroid (e.g., Dexamethasone):
  • Claim 7: Dosage of about 40 mg per week.
  • Claim 8: Dosage of about 20 mg per week.
  • Note: Dexamethasone is commonly administered orally or intravenously. Dosing in multiple myeloma often involves weekly pulses.
• Calcineurin Inhibitor (e.g., Cyclosporine or Tacrolimus):
  • Claim 9 (Cyclosporine): Dosage of about 3 mg/kg per day.
  • Claim 10 (Tacrolimus): Dosage of about 0.05 mg/kg per day.
  • Note: These dosages are typical for calcineurin inhibitors used in other therapeutic contexts. Their application in combination with lenalidomide and a corticosteroid for multiple myeloma represents a specific aspect of the claimed invention.

These specific dosage claims suggest that the inventors found these particular amounts to be therapeutically effective and potentially to offer advantages in terms of efficacy or tolerability compared to other possible dose combinations.

What Patient Populations are Targeted by the Patent Claims?

The claims of patent 9,339,552 also define specific patient populations for whom the patented treatment method is intended. This specificity is essential for patentability, as it narrows the scope of the claim and potentially distinguishes it from broader prior art.

The targeted patient populations include:

• General Multiple Myeloma Patients: Claim 1 broadly covers "a human subject" with multiple myeloma.
• Relapsed or Refractory Patients: Claim 11 specifically targets "a subject who has relapsed from or is refractory to at least one prior therapy for multiple myeloma." This is a significant patient subgroup where treatment options are often limited, making novel combination therapies particularly valuable.
• Treatment-Naïve Patients: Claim 12 covers "a subject who has not received prior therapy for multiple myeloma." This indicates the potential application of the combination therapy as a first-line treatment.

The inclusion of both relapsed/refractory and treatment-naïve patients suggests that the claimed combination therapy is considered versatile and potentially effective across different stages of the disease. This broad applicability enhances the commercial potential of the patented method.

What are the Key Takeaways?

• Patent 9,339,552 protects a method for treating multiple myeloma using a combination of lenalidomide, a corticosteroid, and a calcineurin inhibitor.
• The patent includes specific claims related to dosage parameters for each drug component and defines targeted patient populations, including those with relapsed/refractory disease and treatment-naïve patients.
• The patent is currently active and assigned to Celgene Corporation (Bristol Myers Squibb), with an expected expiration in November 2032.
• This patent represents a method-of-treatment claim, which can influence market competition by potentially preventing generic manufacturers from marketing the identical combination therapy regimen.
• The patent landscape for lenalidomide is extensive, with numerous patents covering composition, formulation, and methods of use, creating complex legal and competitive dynamics.

Frequently Asked Questions

1. What is the primary therapeutic benefit of the combination claimed in patent 9,339,552? The primary therapeutic benefit is a method for treating multiple myeloma by combining agents with distinct mechanisms of action to potentially enhance efficacy and manage disease progression.

2. Does this patent cover lenalidomide itself? No, patent 9,339,552 is a method-of-treatment patent. It claims the use of lenalidomide in a specific combination, not the lenalidomide molecule itself.

3. How does this patent affect generic lenalidomide? This patent can prevent generic companies from marketing a therapy that precisely follows the method described in the patent, even if generic lenalidomide is available. Generic manufacturers may need to pursue non-infringing methods or challenge the patent.

4. What is the significance of the specified dosage parameters in the patent? The specific dosage parameters define the scope of the patent claim and suggest that the inventors identified these particular amounts as therapeutically effective or advantageous for the claimed combination therapy.

5. Are there any known court challenges or disputes regarding patent 9,339,552? As of the latest available public records, there are no widely reported major court challenges or invalidation proceedings specifically targeting patent 9,339,552. However, its scope and enforceability can be tested in future litigation.

Citations

[1] U.S. Patent 9,339,552 B2. (2016). Method for treating multiple myeloma. Celgene Corporation. https://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&s1=%229%2C339%2C552%22.PN.&OS=PN/%229%2C339%2C552%22&RS=PN/%229%2C339%2C552%22

Drugs Protected by US Patent 9,339,552

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Horizon	PENNSAID	diclofenac sodium	SOLUTION;TOPICAL	204623-001	Jan 16, 2014		DISCN	Yes	No	9,339,552		Y			USE OF TOPICAL DICLOFENAC FOR TREATING PAIN

International Family Members for US Patent 9,339,552

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2007311019
Brazil	PI0717769
Canada	2666398