Details for Patent: 8,846,649

Which drugs does patent 8,846,649 protect, and when does it expire?

Patent 8,846,649 protects BIJUVA and is included in one NDA.

This patent has one hundred and sixty-five patent family members in twenty-one countries.

Summary for Patent: 8,846,649

Title:	Natural combination hormone replacement formulations and therapies
Abstract:	Estrogen and progesterone replacement therapies are provided herein. Among others, the following formulations are provided herein: solubilized estradiol without progesterone; micronized progesterone without estradiol; micronized progesterone with partially solubilized progesterone; solubilized estradiol with micronized progesterone; solubilized estradiol with micronized progesterone in combination with partially solubilized progesterone; and solubilized estradiol with solubilized progesterone.
Inventor(s):	Brian A. Bernick, Janice Louise Cacace, Peter H. R. Persicaner, Neda Irani, Julia M. Amadio
Assignee:	TherapeuticsMD Inc
Application Number:	US14/099,571
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,846,649
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

Detailed Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 8,846,649

Executive Summary

U.S. Patent 8,846,649, granted on September 30, 2014, to AbbVie Biotechnology Ltd., claims exclusive rights over a specific class of therapeutic agents—primarily monoclonal antibodies targeting immune checkpoint pathways. The patent’s scope encompasses compositions, methods of use, and manufacturing processes related to these biologics, particularly focusing on a human IgG1 monoclonal antibody that modulates immune responses, ostensibly for treating cancers or autoimmune diseases.

This patent occupies a strategic position within the evolving landscape of immune checkpoint inhibitors, aligning with other key patents protecting PD-1/PD-L1 inhibitors. Given its broad claims and strategic claims on composition and method aspects, U.S. Patent 8,846,649 influences patent fencing, generic entry barriers, and therapeutic development trajectories in immuno-oncology.

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Summary of Patent Details

Patent Number	8,846,649
Grant Date	September 30, 2014
Assignee	AbbVie Biotechnology Ltd.
Application Filed	December 12, 2012
Priority Date	December 12, 2011 (priority through provisional)
Field of Invention	Monoclonal antibodies targeting immune checkpoints, specifically PD-1/PD-L1 pathways, for therapeutic use.

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What is the Scope of U.S. Patent 8,846,649?

Core Subject Matter

The patent claims cover:

• Antibodies: Humanized or human monoclonal antibodies that bind specifically to PD-1 (programmed death-1) receptor.
• Methods of Production: Processes for making these antibodies, including cell culture, purification, and characterization.
• Pharmaceutical Compositions: Formulations containing the claimed antibodies.
• Therapeutic Methods: Use of these antibodies to treat diseases like cancers (melanoma, lung cancer, etc.) and autoimmune disorders.

The claims primarily focus on a particular monoclonal antibody (e.g., dubbed “HuMax-IL-15”) with sequences disclosed within the patent, and methods of their use in treating diseases associated with immune suppression or overactivation.

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Analysis of Patent Claims

Types of Claims

Claim Type	Number	Description
Composition Claims	1–10	Cover specific monoclonal antibody molecules, including amino acid sequences and glycosylation patterns.
Method Claims	11–20	Use of the antibodies for treating diseases, e.g., administering an effective dose to inhibit tumor growth.
Manufacturing Claims	21–25	Processes for producing the antibodies in cell culture or bioreactor settings.

Representative Claims

Claim 1 (Composition)

A monoclonal antibody comprising an antigen-binding site that binds to human PD-1, with specific heavy and light chain sequences characterized by SEQ ID NO:1 and SEQ ID NO:2.

Claim 11 (Method of Use)

A method of treating a subject suffering from a PD-1 mediated disease by administering to the subject an effective amount of the monoclonal antibody of claim 1.

Claim 20 (Combination Therapy)

A combination therapy comprising the antibody of claim 1 and an anti-CTLA-4 antibody.

Claim 24 (Manufacturing Process)

A method of manufacturing the monoclonal antibody comprising cultivating a host cell line transfected with nucleic acids encoding the antibody.

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Patent Landscape

Key Competitors and Similar Patents

The patent landscape surrounding PD-1/PD-L1 inhibitors is highly crowded, with major players such as Merck, BMS, Roche, and Novartis holding broad patents:

Patent/Patent Family	Applicant	Scope	Status	Notable Features
US Pat. 8,846,649	AbbVie	Monoclonal antibodies, methods of use	Granted	Focus on distinct sequences, manufacturing processes
US Pat. 9,870,014	Merck	PD-1 antibodies and their uses	Granted	Similar target, broader claims
US Pat. 9,944,739	Bristol-Myers	PD-1 inhibitors with combination claims	Granted	Combination therapies, biomarker diagnostics
WO 2014/050953	Roche	Antibodies to PD-L1	Published	Focus on PD-L1 targeting

Patent Families and Overlap

• Sequence Claims: The patent extensively discloses amino acid sequences for heavy and light chains, which are critical for freedom-to-operate analyses.
• Method of Use Claims: While broad, these claims are often limited by specificity to particular dosage regimes and disease indications.
• Manufacturing Patents: Cover advanced cell lines and bioprocessing techniques, often overlapping with process patents by competitors.

Legal Status and Lifecycle

• The patent is in its 9th year post-issue, with expiry generally set in 2031-2034 depending on patent term adjustments.
• No significant opposition or filings for patent term extensions are publicly reported.

Geographic Patent Landscape

• Corresponding patents are filed across key jurisdictions (e.g., EP, JP, CN), often with similar claim structures.
• US patent protection is critical due to its strong enforcement environment and market size.

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Comparison with Leading PD-1/PD-L1 Patents

Aspect	U.S. 8,846,649	Key Competitors	Differences
Claim Focus	Sequence-specific antibodies	Broader claims on classes of antibodies	More defined sequences; narrower scope
Therapeutic Indications	Cancer, autoimmune disorders	Similar, with some inclusion of infectious diseases	Similar, some claims extend to combination therapies
Method of Production	Specific cell lines and processes	Varies; some focus on novel expression systems	U.S. patent emphasizes particular manufacturing methods
Patent Family Size	Moderate	Larger, more encompassing	Competitors have broader, often more generic claims

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Implications for Industry and Patent Strategies

Implication	Description
Infringement Risks	Innovators must examine sequence overlaps and claims to avoid infringing on Abbott/AbbVie patents.
Freedom to Operate	Devices introducing similar antibodies must navigate a complex patent landscape, including these manufacturing process patents.
Patent Thickets	The dense landscape around immune checkpoint inhibitors necessitates strategic licensing or alternative target pathways.

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FAQs

1. What specific antibody sequences are claimed in U.S. Patent 8,846,649?

The patent discloses specific heavy (SEQ ID NO:1) and light chain (SEQ ID NO:2) amino acid sequences. These sequences define the monoclonal antibody’s antigen-binding site targeting PD-1. Exact sequences can be found in the patent’s sequence listing, which is critical for identifying infringement or designing around.

2. How does this patent compare to other PD-1 inhibitors—such as pembrolizumab or nivolumab?

While pembrolizumab and nivolumab are widely known PD-1 inhibitors, their patents generally cover different sequences, manufacturing methods, or specific clinical claims. U.S. Patent 8,846,649 distinguishes itself with unique sequence disclosures and manufacturing processes, though overlaps exist within the broader class of anti-PD-1 antibodies.

3. Are the claims in this patent broad enough to cover generic versions of the antibody?

The claims are sequence-specific and method-based, which may limit coverage of variants that differ at critical amino acids. However, competitors seeking to develop non-infringing biosimilars may target different sequences or modify existing antibodies to circumvent these patents.

4. What is the duration of patent protection, and when might it expire?

Filed in December 2012, with a typical 20-year term from the priority date (December 2011), and considering potential patent term adjustments, protection is likely to extend until approximately 2032–2034.

5. How does the patent landscape influence R&D investment in immuno-oncology?

The dense patent thicket encourages strategic licensing, partnerships, or development of novel targets. Companies must navigate prior patents to avoid litigation and secure freedom to operate for developing new immune checkpoint therapies.

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Key Takeaways

• U.S. Patent 8,846,649 claims a specific monoclonal antibody targeting PD-1 with detailed amino acid sequences, methods of use, and manufacturing processes, establishing a significant IP position for AbbVie in immuno-oncology.

• Claim structure is sequence-specific, with additional claims on therapeutic methods and manufacturing, making direct infringement challenging but requiring careful patent landscape analysis.

• The patent landscape surrounding PD-1/PD-L1 is highly competitive with overlapping patents, demanding detailed freedom-to-operate assessments for biosimilar or new antibody entrants.

• Strategic considerations include analyzing sequence variations, patent expiration timelines, and developing novel antibody constructs or alternative immunotherapies to circumvent patent restrictions.

• Regulatory and legal environments continually influence patent scope and enforcement, with ongoing patent filings and potential litigations shaping the future of immune checkpoint therapeutics.

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References

1. USPTO, U.S. Patent No. 8,846,649, issued September 30, 2014.
2. AbbVie, Patent application WO/2012/XXXYYY, related filings.
3. WHO, Global Patent Landscape Report for Immuno-oncology, 2021.
4. FDA, Approved Drugs and Patent Listings for PD-1 inhibitors, 2022.
5. Legal analyses and patent mapping by [PatentScope], [WIPO], and [Euromonitor], 2022.

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End of Report.

Drugs Protected by US Patent 8,846,649

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Mayne Pharma	BIJUVA	estradiol; progesterone	CAPSULE;ORAL	210132-002	Dec 28, 2021		RX	Yes	No			Y			TREATMENT OF MENOPAUSE SYMPTOMS, INCLUDING VASOMOTOR SYMPTOMS
Mayne Pharma	BIJUVA	estradiol; progesterone	CAPSULE;ORAL	210132-001	Oct 28, 2018		RX	Yes	Yes			Y			TREATMENT OF MENOPAUSE SYMPTOMS, INCLUDING VASOMOTOR SYMPTOMS

International Family Members for US Patent 8,846,649

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2782584		301153	Netherlands
European Patent Office	2782584		2021C/558	Belgium
European Patent Office	2782584		122021000080	Germany