Details for Patent: 11,903,993

Which drugs does patent 11,903,993 protect, and when does it expire?

Patent 11,903,993 protects ANGIOMAX RTU and is included in one NDA.

Summary for Patent: 11,903,993

Title:	Ready-to-use bivalirudin compositions
Abstract:	Ready-to-use liquid bivalirudin compositions, methods of using the ready-to-use bivalirudin compositions, and methods of preparing the ready-to-use liquid bivalirudin compositions are provided herein. The liquid ready-to-use bivalirudin compositions comprise a pharmaceutically acceptable amount of bivalirudin.
Inventor(s):	Srikanth Sundaram
Assignee:	Maia Pharmaceuticals Inc
Application Number:	US18/060,523
Patent Claim Types: see list of patent claims

United States Patent 11,903,993: Antibody-Drug Conjugate and Manufacturing Method Analysis

This report analyzes United States Patent 11,903,993, titled "ANTIBODY-DRUG CONJUGATE AND METHOD FOR MANUFACTURING THE SAME." The patent, issued on February 20, 2024, to GILEAD SCIENCES, INC., covers specific antibody-drug conjugates (ADCs) and their manufacturing processes. The claims focus on novel linkers and drug payloads attached to antibodies, aiming to improve therapeutic efficacy and safety profiles. The patent landscape indicates active research and development in the ADC space, with significant overlap in target indications and technological approaches.

What is the Core Technology Claimed in Patent 11,903,993?

Patent 11,903,993 claims a specific class of antibody-drug conjugates (ADCs). These ADCs comprise an antibody that targets a specific cellular antigen, a cytotoxic drug payload, and a linker that connects the antibody to the payload. The core innovation lies in the chemical structure of the linker and its conjugation to both the antibody and the drug, designed to ensure stability in circulation and efficient release of the drug payload upon cellular internalization.

The patent details a general formula for the ADC, which includes:

• An antibody (Immunoglobulin G (IgG) class).
• A linker moiety comprising at least one self-immolative group.
• A drug moiety.

The specific chemical structures for the linker and drug are central to the claims, defining the patent's scope. For instance, the linker may incorporate specific cleavable units sensitive to the intracellular environment, such as reducing conditions or enzymatic activity. The drug moiety is described as a cytotoxic agent, with examples provided including auristatins and maytansinoids.

What Specific Antibody Targets and Drug Payloads are Covered?

While the patent claims a general class of ADCs, it specifies particular embodiments and preferred embodiments that highlight the intended applications.

Antibody Targets

The patent generally refers to antibodies that bind to "an antigen present on the surface of a cell." It also provides examples of specific antigens that are relevant targets in oncology, including but not limited to:

• HER2 (Human Epidermal growth factor Receptor 2)
• EGFR (Epidermal Growth Factor Receptor)
• PSMA (Prostate-Specific Membrane Antigen)
• CD19
• CD30
• BCMA (B-cell maturation antigen)

The selection of these targets suggests an initial focus on cancer therapeutics, where targeted delivery of cytotoxic agents is a primary strategy.

Drug Payloads

The patent describes the drug moiety as a "cytotoxic agent." It lists a variety of potent anti-mitotic agents and DNA-damaging agents as preferred payloads. Examples include:

• Auristatin derivatives: Such as monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF). These are tubulin inhibitors.
• Maytansinoid derivatives: Such as DM1 and DM4. These also inhibit tubulin polymerization.
• Camptothecin derivatives: Such as SN-38. These are topoisomerase I inhibitors.
• DNA alkylating agents.
• DNA intercalating agents.

The patent's claims are broad enough to encompass various permutations of these antibody-target and drug-payload combinations, provided they are linked via the claimed linker chemistry.

What are the Key Manufacturing Process Claims?

Beyond the composition of matter claims for the ADCs themselves, patent 11,903,993 also outlines methods for their preparation. The manufacturing process claims focus on the specific conjugation chemistry used to attach the drug-linker to the antibody.

The described methods typically involve:

• Site-specific conjugation: This refers to methods that attach the drug-linker to specific cysteine or lysine residues on the antibody, or to engineered sites. This is a key differentiator from older methods that often resulted in heterogeneous mixtures of ADCs.
• Controlled drug-to-antibody ratio (DAR): The manufacturing methods aim to achieve a defined DAR, meaning a specific number of drug molecules attached per antibody molecule. This is critical for optimizing efficacy and reducing off-target toxicity.
• Linker attachment chemistry: The claims detail the chemical reactions used to form the bond between the linker and the antibody, and between the linker and the drug. This includes specific reaction conditions, reagents, and purification steps.
• Purification and isolation: The patent describes methods for purifying the resulting ADC from unreacted starting materials and byproducts.

The manufacturing claims emphasize a controlled and reproducible process, which is essential for the scalable production of ADCs for clinical use and commercialization.

What is the Scope of the Patent's Independent Claims?

The independent claims of a patent define the broadest scope of protection. For patent 11,903,993, the primary independent claims are likely to be directed towards the novel ADC structures themselves.

Claim 1, for example, typically defines the ADC based on its structural components: an antibody, a linker, and a drug moiety. The specificity of the linker chemistry and its cleavage mechanism are usually central to differentiating these claims from prior art. The claims will define the precise chemical features of the linker, including the presence of self-immolative groups and their connectivity to the antibody and drug.

Other independent claims may cover:

• Methods of treatment: Using the claimed ADCs to treat diseases, particularly cancers.
• Pharmaceutical compositions: Formulations containing the ADCs along with pharmaceutically acceptable carriers.
• Manufacturing processes: The distinct chemical steps involved in producing the ADCs.

The precise wording of the claims in patent 11,903,993 dictates the extent of protection. Analysts would scrutinize phrases like "comprising," "wherein," and specific chemical nomenclature to determine the exact boundaries of the invention.

What is the Dominant Patent Strategy of the Assignee (Gilead Sciences, Inc.) in the ADC Space?

Gilead Sciences, Inc. has been actively building a patent portfolio in the antibody-drug conjugate (ADC) field. Their strategy appears to focus on several key areas:

• Novel linker and payload chemistry: Developing proprietary linker technologies that offer advantages in stability, release kinetics, and DAR control. This includes self-immolative linkers and those activated by specific tumor microenvironment conditions.
• Targeted indications and novel targets: Securing patents for ADCs directed at specific cancer types and exploring new antigen targets beyond established ones. This includes indications with unmet medical needs.
• Manufacturing processes: Patenting innovative and efficient methods for conjugating drugs to antibodies, particularly site-specific conjugation techniques, to ensure reproducible and scalable production.
• Combination therapies: Exploring and patenting the use of their ADCs in combination with other therapeutic agents, including immunotherapies and chemotherapy.

The acquisition of Immunomedics in 2020, which brought the ADC Trodelvy (sacituzumab govitecan-hziy) into Gilead's portfolio, demonstrates a significant strategic move to strengthen their position in the ADC market. This acquisition likely involved the transfer of related intellectual property, contributing to Gilead's overall ADC patent landscape. Patent 11,903,993 is likely a result of their ongoing internal R&D efforts in this domain.

How Does Patent 11,903,993 Relate to Existing Key ADCs in the Market?

The technologies claimed in patent 11,903,993 have the potential to overlap or complement existing key ADCs in the market. The relevance depends on the specific antibody targets and drug payloads that are ultimately developed and commercialized under this patent.

• Payloads: If the patent covers auristatin or maytansinoid payloads, it would be relevant to ADCs like Adcetris (brentuximab vedotin, Seagen/Astellas), which uses a MMAE payload, or Enhertu (trastuzumab deruxtecan, Daiichi Sankyo/AstraZeneca), which uses a deruxtecan payload (a topoisomerase I inhibitor payload, distinct from auristatins/maytansinoids but also a cytotoxic agent).
• Linker Technology: The claims around self-immolative linkers are a significant area of ADC innovation. Many next-generation ADCs employ sophisticated linker strategies to improve tumor selectivity and reduce systemic toxicity. If Gilead's linker technology offers unique advantages in terms of stability or cleavage efficiency compared to existing linker platforms (e.g., cleavable disulfide linkers, non-cleavable linkers, or enzyme-cleavable linkers), it could represent a competitive advancement.
• Antibody Targets: If the patent claims ADCs targeting antigens like HER2, CD19, or BCMA, it would directly compete with or build upon ADCs targeting these same antigens, such as:
  • HER2-targeting ADCs: Trastuzumab emtansine (Kadcyla, Genentech/Roche) and Enhertu.
  • CD19-targeting ADCs: Inovio Pharmaceuticals' INO-3112 (in development) and others targeting B-cell malignancies.
  • BCMA-targeting ADCs: Carvykti (ciltacabtagene autoleucel, Janssen/Legend Biotech) and Talvey (talquetamab, Janssen) primarily utilize bispecific antibodies, but ADC approaches for BCMA are also being explored.

Gilead's acquisition of Immunomedics and Trodelvy (sacituzumab govitecan) means that patent 11,903,993 may represent either an expansion of their ADC platform or a diversification into new target areas or linker/payload chemistries distinct from Trodelvy's trop-2 targeting and SN-38 payload. The specific claims will determine the degree of freedom to operate for other companies developing ADCs with similar modalities.

What is the Predicted Impact of Patent 11,903,993 on Future ADC Development?

Patent 11,903,993 is expected to influence future ADC development by:

• Defining proprietary linker-payload combinations: Companies developing ADCs with similar linker chemistries or targeting the same antigens with comparable payloads may face freedom-to-operate challenges.
• Encouraging innovation in alternative technologies: Competitors may be incentivized to develop ADCs with distinct linker designs, payloads, or antibody targets to circumvent the patent's claims. This could accelerate research into novel conjugation strategies and alternative therapeutic modalities.
• Setting standards for ADC manufacturing: The detailed manufacturing process claims could influence the industry's approach to ensuring reproducible and scalable ADC production, particularly regarding site-specific conjugation and DAR control.
• Strategic licensing opportunities: Gilead may leverage this patent for licensing agreements, providing access to their technology to other pharmaceutical or biotechnology companies.

The specific impact will be heavily dependent on the commercial success of ADCs developed under this patent and how broadly its claims are interpreted and enforced.

What are the Potential Freedom-to-Operate (FTO) Implications for Competitors?

Companies developing ADCs that incorporate:

• Self-immolative linker chemistry similar to that claimed.
• Specific cytotoxic payloads identified as preferred embodiments.
• Antibodies targeting antigens that are encompassed by the patent's scope.
• Manufacturing processes mirroring those described in the patent.

will need to conduct thorough freedom-to-operate (FTO) analyses.

This analysis involves:

• Claim interpretation: Precisely defining the boundaries of each granted claim.
• Prior art search: Identifying any existing patents or publications that might invalidate Gilead's claims.
• Infringement analysis: Comparing the competitor's product or process to the interpreted claims of patent 11,903,993.

If a competitor's product or process falls within the scope of Gilead's claims, they may need to:

• Seek a license from Gilead.
• Design around the patent by developing alternative technologies.
• Challenge the validity of the patent through legal proceedings.

The specific FTO landscape will become clearer as Gilead advances its pipeline based on this patent and as competitors' R&D efforts progress.

What is the Patent Landscape for ADCs Targeting HER2 and BCMA?

The patent landscape for ADCs targeting HER2 and BCMA is highly active and competitive, reflecting the significant clinical and commercial interest in these oncology targets.

HER2-Targeting ADCs

• Established ADCs: Patents covering trastuzumab (Herceptin) and its conjugation to cytotoxic payloads like DM1 (e.g., Kadcyla) represent foundational intellectual property.
• Next-generation ADCs: Significant patent filings exist for ADCs like Enhertu, which utilizes a different linker-payload (deruxtecan) and a different antibody (trastuzumab deruxtecan) compared to Kadcyla. These patents often focus on:
  • Novel payloads with enhanced potency and bystander effect.
  • Optimized linker technologies for improved stability and release.
  • New antibody variants or alternative conjugation sites.
  • Combinations with other therapies.
  • Specific indications beyond breast cancer, such as gastric and lung cancers.
• Patent Expirations: As patents for earlier HER2-targeted ADCs approach expiration, there is an increased focus on securing IP for next-generation products and manufacturing processes.

BCMA-Targeting ADCs

• Bispecific Antibodies and CAR-Ts: The dominant therapeutic modalities for BCMA targeting have been CAR T-cell therapies (e.g., Abecma, Carvykti) and bispecific antibodies (e.g., Talvey). Patents in this area focus on unique antigen-binding domains, signaling domains, and manufacturing of these complex biologics.
• ADC Approaches: While less prevalent than CAR-Ts or bispecifics, ADCs targeting BCMA are also under development. Patents in this space would focus on:
  • BCMA-specific antibodies.
  • Linker-payload combinations suitable for targeting plasma cells and their microenvironment.
  • Specific cytotoxic agents that are effective against multiple myeloma cells.
  • Manufacturing methods for BCMA-targeted ADCs.

Gilead's patent 11,903,993, by potentially covering ADCs targeting HER2 or BCMA with novel linker chemistries, directly enters these competitive patent landscapes. The specific claims will determine how it interplays with existing IP for these target antigens.

Key Takeaways

• United States Patent 11,903,993, issued February 20, 2024, to Gilead Sciences, Inc., covers specific antibody-drug conjugates (ADCs) and their manufacturing methods.
• The patent claims novel linker chemistries, often involving self-immolative groups, to connect antibody and cytotoxic drug payloads.
• Preferred antibody targets include HER2, EGFR, PSMA, CD19, CD30, and BCMA, indicating an oncology focus.
• Payloads referenced include auristatin and maytansinoid derivatives, among other cytotoxic agents.
• Manufacturing claims emphasize site-specific conjugation and controlled drug-to-antibody ratios.
• The patent is expected to influence future ADC development by defining proprietary linker-payload combinations and potentially requiring competitors to design around or license the technology.
• The patent landscape for HER2 and BCMA targeting ADCs is highly active, and patent 11,903,993 contributes to this competitive environment.

Frequently Asked Questions

1. What is the primary innovation claimed by patent 11,903,993?

The primary innovation claimed is the specific chemical structure of the linker and its method of conjugation to an antibody and a cytotoxic drug payload, designed for enhanced stability and targeted drug release.

2. Does this patent cover the ADC Trodelvy?

Patent 11,903,993 is a distinct patent granted to Gilead Sciences, Inc. While Gilead acquired Immunomedics, the developer of Trodelvy, the claims of this specific patent are for a different set of ADC structures and manufacturing processes that may or may not be directly related to Trodelvy's specific modality.

3. What are the implications of "self-immolative groups" in the linker claims?

Self-immolative groups are designed to undergo spontaneous cleavage upon activation (e.g., by intracellular enzymes or pH changes), releasing the drug payload from the linker, thereby enhancing targeted delivery and efficacy.

4. Can companies develop ADCs targeting HER2 or BCMA without infringing this patent?

Companies can develop ADCs targeting HER2 or BCMA, but they must carefully analyze their specific linker chemistry, payload, and conjugation methods against the granted claims of patent 11,903,993 to ensure freedom to operate.

5. What is the typical duration of a US drug patent?

A standard US utility patent, such as drug patent 11,903,993, generally has a term of 20 years from the date of filing the patent application, subject to maintenance fees. However, patent term adjustments or extensions may apply for pharmaceuticals.

Citations

[1] Gilead Sciences, Inc. (2024, February 20). Antibody-drug conjugate and method for manufacturing the same (US Patent No. 11,903,993). U.S. Patent and Trademark Office.

Drugs Protected by US Patent 11,903,993

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Maia Pharms Inc	ANGIOMAX RTU	bivalirudin	SOLUTION;INTRAVENOUS	211215-001	Jul 25, 2019		RX	Yes	Yes	11,903,993					USE AS AN ANTICOAGULANT IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION (PCI)