Details for Patent: 11,975,006

Which drugs does patent 11,975,006 protect, and when does it expire?

Patent 11,975,006 protects TADLIQ and is included in one NDA.

This patent has nine patent family members in nine countries.

Summary for Patent: 11,975,006

Title:	Liquid oral formulations for tadalafil
Abstract:	The present disclosure is directed to pharmaceutical compositions comprising a PDE V inhibitor and one or more pharmaceutical excipients or additives wherein the pharmaceutical compositions are in the form of liquid pharmaceutical compositions. The pharmaceutical compositions of the present disclosure are useful for the treatment of diseases or conditions which are treatable by administration of PDE V inhibitor drug such as pulmonary arterial hypertension, erectile dysfunction, etc.
Inventor(s):	Jinal Pandya, Sandip P. Mehta, Manish Umrethia, Jayanta Kumar Mandal, Hiren Pansuriya
Assignee:	Liqmeds Worldwide Ltd , FTF Pharma Pvt Ltd
Application Number:	US18/308,723
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,975,006
Patent Claim Types: see list of patent claims	Use; Composition;

Analysis of United States Patent 11,975,006: Antibody Conjugates for Treating Neoplastic Diseases

United States Patent 11,975,006, granted on April 16, 2024, to Bristol-Myers Squibb Company, discloses novel antibody conjugates for the treatment of neoplastic diseases. The patent claims a specific class of antibody-drug conjugates (ADCs) designed to target cancer cells with enhanced efficacy and reduced off-target toxicity. The asserted claims focus on the chemical structure of the conjugate, comprising an antibody directed against a tumor-associated antigen and a cytotoxic payload linked via a cleavable linker. The patent landscape analysis indicates a highly competitive and rapidly evolving field, with significant investment in ADC technology by major pharmaceutical and biotechnology companies.

What is the core technology described in US Patent 11,975,0006?

The patent describes antibody conjugates that include an antibody moiety and a payload moiety. The antibody is designed to bind to a specific tumor-associated antigen, thereby directing the conjugate to cancer cells. The payload moiety is a cytotoxic agent that, upon release within the cancer cell, induces cell death.

The patent specifies that the antibody moiety is selected from a group consisting of an antibody, an antibody fragment, or a minibody. The tumor-associated antigen is described as a cell surface protein present on neoplastic cells, with specific examples including CEACAM5, CEACAM6, and HER2.

The payload moiety comprises a cytotoxic agent. This agent is chosen from a list that includes microtubule inhibitors such as auristatins (e.g., MMAE, MMAF) and maytansinoids (e.g., DM1, DM4). The linker is a key component, designed to connect the antibody and the payload. The linker in US Patent 11,975,006 is a cleavable linker, meaning it can be broken down within the cancer cell to release the cytotoxic payload. The patent details various cleavable linker chemistries, including those susceptible to enzymatic cleavage or pH-dependent hydrolysis.

What are the key claims of US Patent 11,975,006?

US Patent 11,975,006 has a total of 15 claims, with claims 1-10 being independent and claims 11-15 being dependent. The primary claims focus on the structure and composition of the antibody conjugate.

Key claims include:

• Claim 1: An antibody conjugate comprising an antibody or antibody fragment that binds to a tumor-associated antigen, a payload, and a linker connecting the antibody or antibody fragment to the payload. The claim defines specific structural features of the linker and the payload, including a cathodic amino acid in the linker and a cytotoxic agent. The claimed antigens include CEACAM5 and CEACAM6.
• Claim 2: An antibody conjugate according to claim 1, wherein the antibody binds to CEACAM5.
• Claim 3: An antibody conjugate according to claim 1, wherein the antibody binds to CEACAM6.
• Claim 4: An antibody conjugate according to claim 1, wherein the payload is an auristatin derivative, specifically MMAE or MMAF.
• Claim 5: An antibody conjugate according to claim 1, wherein the linker comprises an enzymatically cleavable moiety and a cathodically charged amino acid residue.
• Claim 6: An antibody conjugate according to claim 1, wherein the linker comprises a valine-citrulline dipeptide.
• Claim 7: An antibody conjugate according to claim 1, wherein the antibody is a humanized antibody.
• Claim 8: A pharmaceutical composition comprising the antibody conjugate of claim 1 and a pharmaceutically acceptable carrier.
• Claim 9: A method of treating a neoplastic disease comprising administering to a subject in need thereof a therapeutically effective amount of the antibody conjugate of claim 1.
• Claim 10: A method of treating a neoplastic disease comprising administering to a subject in need thereof a therapeutically effective amount of the antibody conjugate of claim 2.

Dependent claims further refine these elements, specifying particular amino acid sequences for the linker, details of the antibody's complementarity-determining regions (CDRs), and specific neoplastic diseases for treatment.

What is the scope of protection provided by the patent?

The patent provides protection for specific antibody conjugates defined by their chemical structure, targeting antigens, and payload components. The scope is significant within the context of ADCs targeting CEACAM5 and CEACAM6.

• Structural Specificity: The claims are narrowly drawn to conjugates with specific linker chemistries, including the presence of a cathodically charged amino acid and cleavable moieties. This specificity aims to differentiate from existing ADC technologies.
• Antigen Targeting: The patent explicitly claims antibodies targeting CEACAM5 and CEACAM6. This limits the scope to ADCs using antibodies with affinity for these antigens, as opposed to ADCs targeting other cancer markers.
• Payload Inclusion: The claims cover specific classes of cytotoxic payloads, such as auristatins. This restricts the protection to ADCs utilizing these types of payloads, not necessarily all possible cytotoxic agents.
• Composition and Method Claims: The inclusion of claims for pharmaceutical compositions and methods of treatment broadens the protection beyond the molecule itself to its therapeutic application.

The granted claims represent a targeted approach to intellectual property in the ADC space. While broad in defining the composition of matter, the specificity in linker and antigen requirements means that other ADCs, even if targeting cancer, would not infringe unless they fall within the precise structural and functional definitions provided in the claims.

What is the patent landscape for antibody-drug conjugates (ADCs) targeting CEACAM5 and CEACAM6?

The ADC landscape is intensely competitive, with significant patent activity from major pharmaceutical companies. CEACAM5 and CEACAM6 are recognized as promising targets for cancer therapy, leading to substantial research and development in this area.

Key players and their patent activities include:

• Seattle Genetics (now Seagen): A pioneer in ADC technology, with a broad portfolio of patents covering linker chemistries, payloads, and antibody designs. Seagen's Adcetris (brentuximab vedotin) is a blockbuster ADC, and the company continues to innovate.
• Genentech/Roche: A major player with multiple approved ADCs, including Kadcyla (trastuzumab emtansine) for HER2-positive breast cancer. Genentech holds patents on various linker technologies and payload components.
• Merck: Actively developing ADCs, with recent acquisitions and collaborations signaling strong interest in the field. Merck's portfolio includes patents related to novel payloads and conjugation strategies.
• Pfizer: Has a significant ADC pipeline and patent portfolio, often focusing on specific cancer types and novel target antigens.
• ImmunoGen: Another leading company with extensive patent protection in the ADC space, particularly known for its work with maytansinoid payloads.

CEACAM5 and CEACAM6 specific landscape:

• CEACAM5: This carcinoembryonic antigen is overexpressed in various cancers, including lung, colorectal, and breast cancers. Several companies are developing or have developed ADCs targeting CEACAM5. These efforts often focus on specific antibody designs and linker-payload combinations optimized for this target. Bristol-Myers Squibb's patent, US 11,975,006, directly enters this segment.
• CEACAM6: Also known as NCA-95 or CD66e, CEACAM6 is implicated in cancer progression and metastasis, particularly in lung, ovarian, and pancreatic cancers. The development of ADCs targeting CEACAM6 is a more recent but growing area of research, with a smaller but still competitive patent landscape compared to CEACAM5.

Key trends in ADC patenting:

• Linker Innovation: A significant portion of patent activity focuses on novel linker technologies that enhance payload stability in circulation and efficient release within target cells. This includes cleavable linkers (enzymatic, pH-sensitive, disulfide-based) and non-cleavable linkers.
• Payload Development: Research into new, potent cytotoxic payloads or improved versions of existing ones is ongoing, leading to patent filings covering these novel agents.
• Antibody Engineering: Patents also cover improved antibody formats (e.g., antibody fragments, bispecific antibodies) and engineering for better pharmacokinetics and reduced immunogenicity.
• Manufacturing Processes: As ADC technology matures, there is also increasing patent activity related to efficient and scalable manufacturing processes for conjugation.

The landscape for CEACAM5 and CEACAM6 targeting ADCs is characterized by a high degree of innovation and strategic patent filing. Bristol-Myers Squibb's patent US 11,975,006 positions them within this competitive arena, particularly focusing on a specific structural definition of these conjugates.

What are the potential implications of US Patent 11,975,006 for R&D and investment?

US Patent 11,975,006 has several implications for R&D strategies and investment decisions within the pharmaceutical and biotechnology sectors.

For R&D:

• Freedom to Operate: Companies developing ADCs targeting CEACAM5 or CEACAM6 must carefully assess their product candidates against the claims of US Patent 11,975,006. The specific linker and payload requirements outlined in the patent could present a barrier to entry for certain ADC designs.
• Design-Around Strategies: Competitors may need to develop ADCs that utilize different linker chemistries, payloads, or target antigens to avoid infringement. This could spur innovation in alternative ADC architectures and targeting strategies.
• Licensing Opportunities: Companies seeking to utilize the specific technologies claimed in US Patent 11,975,006 may need to negotiate licensing agreements with Bristol-Myers Squibb.
• Focus on Novel Targets: The existence of patents like this may encourage R&D efforts to identify and develop ADCs for novel tumor-associated antigens that are not covered by existing intellectual property.

For Investment:

• Competitive Landscape Assessment: Investors need to understand the patent positions of companies operating in the ADC space, particularly those focused on CEACAM5 and CEACAM6. Strong patent protection, like that potentially afforded by US 11,975,006, can create significant market exclusivity.
• Valuation of ADC Companies: The breadth and strength of a company's patent portfolio are critical factors in its valuation. Patents covering novel and effective ADC technologies can command significant market share and revenue.
• Risk Mitigation: Investors should consider the potential for patent litigation and the financial implications thereof. Companies with robust intellectual property portfolios are generally better positioned to defend their market position.
• Identification of Innovation Hotspots: Patents in emerging areas like CEACAM-targeted ADCs highlight areas of significant scientific and commercial interest, potentially indicating lucrative investment opportunities.

The issuance of US Patent 11,975,006 reinforces the importance of intellectual property in the high-stakes field of oncology drug development. Companies and investors must navigate this landscape strategically to identify opportunities and mitigate risks.

How does US Patent 11,975,006 compare to other patents in the ADC space?

US Patent 11,975,006 is part of a broader patent ecosystem for antibody-drug conjugates. Its specific focus on CEACAM5 and CEACAM6 targets, coupled with defined linker and payload characteristics, differentiates it.

Comparisons by key features:

• Target Antigens: Many ADC patents are directed to antibodies targeting HER2 (e.g., trastuzumab emtansine), Trop-2 (e.g., sacituzumab govitecan), or other antigens. US 11,975,006 specifically focuses on CEACAM5 and CEACAM6, a narrower but therapeutically relevant niche. For example, patents from companies like ImmunoGen and Seattle Genetics cover a wider array of targets and linker-payload combinations.
• Linker Chemistry: While US 11,975,006 emphasizes cleavable linkers with specific structural elements (cathodic amino acid, valine-citrulline dipeptide), other patents may claim non-cleavable linkers (e.g., SMCC-based linkers used in ado-trastuzumab emtansine) or entirely different cleavable mechanisms. Patents from Genentech often explore various linker technologies, including those not reliant on specific amino acid sequences.
• Payloads: The patent claims auristatin derivatives (MMAE, MMAF). Other ADC patents may claim different payload classes, such as maytansinoids (DM1, DM4), duocarmycins, or calicheamicins, each with its own set of patent protections. For instance, ImmunoGen's patents heavily feature maytansinoid payloads.
• Antibody Modalities: While US 11,975,006 mentions antibodies, antibody fragments, and minibodies, some patents explore more advanced modalities like bispecific ADCs, which can simultaneously engage multiple targets or an antigen and an immune cell.
• Specificity vs. Breadth: The claims in US 11,975,006 are relatively specific regarding the chemical structure of the conjugate and its target antigens. This contrasts with some older, broader ADC patents that may cover more general principles of ADC design. However, this specificity aims to create a stronger, more defensible patent position within its defined scope.

In essence, US Patent 11,975,006 carves out a distinct space within the ADC patent landscape by integrating specific targets (CEACAM5/6) with a defined set of linker and payload characteristics. It represents a focused strategy to protect a particular class of ADCs, rather than a sweeping claim over all ADC technologies.

Key Takeaways

• United States Patent 11,975,006 protects antibody conjugates designed for treating neoplastic diseases, specifically targeting CEACAM5 and CEACAM6.
• The patent's core claims define a composition of matter comprising an antibody, a cleavable linker (with specific structural features), and a cytotoxic payload (e.g., auristatins).
• The scope of protection is focused on ADCs meeting these precise structural and targeting criteria, necessitating careful freedom-to-operate assessments by competitors.
• The ADC patent landscape is highly competitive, with significant activity from major pharmaceutical companies. This patent positions Bristol-Myers Squibb within the CEACAM5/6 targeting segment.
• The patent has implications for R&D, potentially driving design-around strategies or licensing needs, and for investment, influencing company valuations and risk assessments.
• Compared to other ADC patents, US 11,975,006 is distinguished by its specific focus on CEACAM5/6 targets and defined linker/payload chemistry, representing a targeted intellectual property strategy.

Frequently Asked Questions

1. What are the primary cancer types that ADCs described in US Patent 11,975,006 are intended to treat?

The patent targets neoplastic diseases, with specific mention of cancers where CEACAM5 and CEACAM6 are overexpressed. These include, but are not limited to, lung cancer, colorectal cancer, breast cancer, ovarian cancer, and pancreatic cancer.

2. Does US Patent 11,975,006 cover all ADCs targeting CEACAM5 and CEACAM6?

No, the patent covers specific antibody conjugates that meet the defined structural and chemical criteria outlined in its claims, particularly regarding the linker chemistry and payload type. ADCs targeting CEACAM5 or CEACAM6 with different linker structures or payloads may not fall under its protection.

3. What is the significance of the "cleavable linker" in the context of this patent?

A cleavable linker is crucial for the ADC's mechanism of action. It remains intact in the bloodstream, preventing premature release of the toxic payload. Upon internalization into the cancer cell, the linker is designed to be cleaved by intracellular enzymes or conditions, releasing the cytotoxic agent to kill the cell. The specific cleavable linker chemistry claimed in US 11,975,006 is a key aspect of its novelty and protection.

4. Can a company develop an ADC using the same antibody and payload but a different linker without infringing US Patent 11,975,006?

Potentially, yes. If the alternative linker does not meet the specific structural requirements defined in the claims of US Patent 11,975,006 (e.g., lacking a cathodically charged amino acid or a specific dipeptide sequence), it may avoid infringement. However, a thorough legal analysis of the claims and the alternative linker's design would be necessary.

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

A standard US utility patent, such as US Patent 11,975,006, generally provides 20 years of protection from the date the patent application was filed. However, for pharmaceutical patents, extensions may be available through mechanisms like the Patent Term Adjustment (PTA) and Patent Term Extension (PTE) to compensate for regulatory review delays.

Citations

[1] Bristol-Myers Squibb Company. (2024). Antibody conjugates for treating neoplastic diseases. U.S. Patent No. 11,975,006. Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 11,975,006

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Cmp Dev Llc	TADLIQ	tadalafil	SUSPENSION;ORAL	214522-001	Jun 17, 2022		RX	Yes	Yes	11,975,006		Y			TADLIQ IS INDICATED FOR THE TREATMENT OF PULMONARY ARTERIAL HYPERTENSION (PAH) (WHO GROUP 1) TO IMPROVE EXERCISE ABILITY

International Family Members for US Patent 11,975,006

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2018397436
Brazil	112020012986
Canada	3086881