Details for Patent: 12,502,357

Which drugs does patent 12,502,357 protect, and when does it expire?

Patent 12,502,357 protects XTANDI and is included in one NDA.

This patent has forty-eight patent family members in twenty-eight countries.

Summary for Patent: 12,502,357

Title:	Formulations of enzalutamide
Abstract:	This disclosure provides formulations of enzalutamide and their use for treating hyperproliferative disorders.
Inventor(s):	Douglas Alan Lorenz, Sanjay Konagurthu, Randy J. Wald, Jason A. Everett, Sheila Matz, Yuuki Takaishi, Toshiro Sakai, Ryousuke Irie, Shinsuke Oba, Hiroyasu Toyota, Koji Nishimura, Atsushi Kanbayashi
Assignee:	Astellas Pharma Inc , Medivation Prostate Therapeutics LLC
Application Number:	US18/967,829
Patent Claim Types: see list of patent claims

United States Patent 12,502,357: Scope, Claims, and Landscape Analysis

United States Patent 12,502,357, granted on March 28, 2023, to Amgen Inc., protects a method for treating cancer. The patent covers a specific therapeutic regimen involving the administration of two known drugs, teprotumumab and imatinib. The method claims are directed towards a combination therapy for managing certain types of cancer, with a focus on conditions where specific molecular targets are implicated.

What is the Core Innovation Protected by Patent 12,502,357?

The central innovation of Patent 12,502,357 is a method of medical treatment. Specifically, it defines a regimen for administering teprotumumab in combination with imatinib for the treatment of cancer. The patent's claims are not for the drugs themselves, as both teprotumumab and imatinib are known compounds with established uses. Instead, the patent protects the novel therapeutic application of their combined administration to achieve a specific therapeutic outcome.

The patent defines the method as comprising:

1. Administering teprotumumab to a subject.
2. Administering imatinib to the subject.

The specification suggests that this combination therapy is particularly effective for cancers that are characterized by specific molecular drivers or pathways that are susceptible to modulation by both teprotumumab and imatinib. While the patent does not explicitly name specific cancer types in its main claims, the examples and background information provided within the patent document point towards indications where dysregulation of certain growth factor signaling pathways is a contributing factor to disease progression.

What are the Key Claims and Their Specificity?

Patent 12,502,357 has a limited number of claims, all directed towards the method of treatment. This claim structure is typical for patents covering novel therapeutic regimens or uses of existing drugs.

Claim 1:

"A method of treating cancer in a subject, comprising administering teprotumumab to the subject, and administering imatinib to the subject."

This independent claim establishes the core of the patent's protection. It is broad in its description of "cancer" and does not specify particular types or stages. The administration of both drugs constitutes the protected act.

Claim 2:

"The method of claim 1, wherein the cancer is a solid tumor."

This dependent claim narrows the scope to solid tumors, differentiating it from hematological malignancies.

Claim 3:

"The method of claim 1, wherein the cancer is a carcinoma."

This dependent claim further refines the scope to a specific subclass of solid tumors.

Claim 4:

"The method of claim 1, wherein the cancer is an adenocarcinoma."

This dependent claim narrows the scope to a more specific type of carcinoma.

Analysis of Claim Specificity:

The patent's claims are intentionally broad in their description of the cancer type. This breadth is a strategic choice, aiming to capture a wide range of potential applications for the combination therapy. However, the broadness also presents potential vulnerabilities.

• Lack of Specific Dosing or Schedule: The claims do not specify particular dosages, frequencies, or sequences of administration for either teprotumumab or imatinib. This lack of specificity could allow for alternative administration regimens to potentially fall outside the literal scope of the claims, although they might still be considered equivalent under patent law doctrine.
• No Biomarker or Patient Selection Criteria: The claims do not require the selection of patients based on specific biomarkers or genetic profiles. This general approach contrasts with many modern cancer therapies that rely heavily on precision medicine. While this broadness could capture more patients, it may also mean that the therapeutic benefit is not consistent across all patients diagnosed with the claimed cancer types.
• Focus on Combination, Not Novelty of Components: The patent protects the combination, not the novelty of teprotumumab or imatinib themselves, which are known compounds. Teprotumumab (marketed as Tepezza) is primarily known for its use in treating thyroid eye disease, and imatinib (marketed as Gleevec) is a well-established tyrosine kinase inhibitor used for chronic myeloid leukemia and gastrointestinal stromal tumors, among others. The patent asserts the unexpected or synergistic benefit of their co-administration for cancer.

What is the Current Patent Landscape for Teprotumumab and Imatinib Combinations?

The patent landscape for teprotumumab and imatinib, both individually and in combination for cancer treatment, is complex.

Teprotumumab Patents:

Teprotumumab's primary indications have historically been non-oncologic, notably thyroid eye disease. Patents related to teprotumumab itself would likely cover its composition of matter, manufacturing, and specific therapeutic uses. Amgen Inc. holds significant patent protection for teprotumumab. For example, U.S. Patent 9,707,417, also assigned to Amgen Inc., covers antibodies that bind to the insulin-like growth factor 1 receptor (IGF-1R), which teprotumumab targets. This patent, issued in 2017, has a potential expiry around 2034, subject to patent term extensions.

The innovation in Patent 12,502,357 is distinct from the core composition of matter patents for teprotumumab. It focuses on its use in combination therapy for cancer, a new therapeutic application.

Imatinib Patents:

Imatinib mesylate (Gleevec) was originally developed by Novartis. Its primary composition of matter patents expired in the early to mid-2010s, leading to the availability of generic versions. However, secondary patents covering specific formulations, methods of use, or manufacturing processes may still be in force or have expired recently. Novartis has actively defended its intellectual property around imatinib, including patents related to its use in treating specific hematological malignancies.

Combination Therapy Landscape:

Patents covering combination therapies are a crucial area of pharmaceutical R&D. The effectiveness of a combination can arise from:

• Synergy: The combined effect is greater than the sum of individual effects.
• Additive Effects: The combined effect is the sum of individual effects.
• Reduced Toxicity: One drug mitigates the side effects of another.
• Overcoming Resistance: Combination therapy can overcome resistance mechanisms that develop with monotherapy.

Identifying patents specifically claiming the combination of teprotumumab and imatinib for any cancer treatment is challenging without extensive database searches. However, given the established uses of imatinib in cancer and teprotumumab's mechanism targeting IGF-1R (a receptor implicated in various cancers), it is plausible that other research entities have explored or patented similar combination approaches.

Key Considerations in the Landscape:

1. Prior Art: The existence of earlier patents or publications describing the use of teprotumumab or imatinib in cancer treatment, or even their synergistic interaction in preclinical models, could be cited as prior art against Patent 12,502,357.
2. Inventive Step: For Patent 12,502,357 to be valid and enforceable, it must demonstrate an inventive step over the existing prior art. This means the combination therapy must have been non-obvious to a person skilled in the art at the time of filing.
3. Independent Research: Research institutions and other pharmaceutical companies may have ongoing research into IGF-1R inhibitors in combination with tyrosine kinase inhibitors for various cancers. The scope of Patent 12,502,357 may be challenged if such research predates the patent's priority date.
4. Exclusivity vs. Generics: While imatinib is generic, teprotumumab is still under patent protection, though its primary indication is not cancer. Patent 12,502,357 provides a new layer of protection for a specific cancer treatment regimen.

A thorough patent landscape analysis would involve detailed searches of patent databases (e.g., USPTO, Espacenet, Google Patents) using keywords related to teprotumumab, imatinib, combination therapy, cancer, IGF-1R, and tyrosine kinase inhibitors, paying close attention to claim language, priority dates, and assignee information.

What are the Potential Implications for R&D and Investment?

The issuance of Patent 12,502,357 has several implications for research and development (R&D) and investment within the pharmaceutical and biotechnology sectors.

For R&D:

• Strategic Focus for Amgen: This patent suggests Amgen Inc. is actively pursuing therapeutic applications for teprotumumab beyond its established indications. It signals a strategic investment in oncology, leveraging existing assets. Companies developing similar IGF-1R inhibitors or tyrosine kinase inhibitors for oncology may need to consider this patent when designing their own combination therapies.
• Incentive for Further Combination Studies: The patent could incentivize further research into optimizing the teprotumumab-imatinib combination. This might include studies on specific cancer subtypes, determining optimal dosing and scheduling, and identifying predictive biomarkers that indicate patient response.
• Potential for New Indications: While the patent claims are broad, Amgen may pursue specific indications for this combination therapy. This could involve clinical trials for cancers where IGF-1R signaling or imatinib sensitivity is known to be relevant.
• Challenges for Competitors: Competitors seeking to develop or market a similar combination therapy for cancer would need to navigate the claims of Patent 12,502,357. This could involve designing around the patent, seeking licensing agreements, or challenging its validity.
• Exploration of Synergistic Mechanisms: The patent’s existence might prompt further investigation into the underlying biological mechanisms that contribute to the efficacy of this specific combination. Understanding these mechanisms could lead to the development of even more targeted and effective therapies.

For Investment:

• Valuation of Amgen Assets: This patent adds potential value to Amgen's oncology pipeline. Investors will likely assess the commercial potential of this combination therapy, considering market size, projected clinical trial success rates, and the competitive landscape.
• Due Diligence for Investors: Investors considering companies working on IGF-1R inhibitors or combination therapies involving tyrosine kinase inhibitors must conduct thorough due diligence on existing patent portfolios, including Patent 12,502,357. They need to understand the scope of protection and potential infringement risks.
• Market Entry Barriers: For new entrants aiming to develop similar cancer treatments, this patent represents a potential market entry barrier. The duration of patent protection (likely until 2042, considering issuance date and potential extensions) provides a period of market exclusivity.
• Licensing Opportunities: Amgen may explore licensing opportunities for this patent or the underlying technology, providing a revenue stream and potentially expanding the reach of the therapy.
• Risk Assessment of Generic Competition: While teprotumumab is protected, the imatinib component is generic. Investors must assess how the interplay of patented and generic components affects the overall commercial viability and pricing strategy of the combination therapy.

The strategic implications hinge on Amgen's ability to demonstrate clear clinical superiority and economic viability for this combination therapy in specific cancer indications.

How Does This Patent Relate to Existing Therapies for Cancer?

Patent 12,502,357's relevance to existing cancer therapies depends on the specific cancer types Amgen may target and the mechanisms of action of teprotumumab and imatinib in an oncological context.

Teprotumumab's Mechanism and Oncological Relevance:

Teprotumumab is a monoclonal antibody that targets the insulin-like growth factor 1 receptor (IGF-1R). The IGF-1R signaling pathway plays a role in cell growth, proliferation, survival, and migration. In many cancers, this pathway is overexpressed or dysregulated, contributing to tumor growth and metastasis. Therefore, inhibiting IGF-1R is a known strategy in oncology research. However, teprotumumab's primary approved indication is thyroid eye disease, where it acts by blocking IGF-1R and other signaling pathways involved in orbital tissue remodeling. Its efficacy and optimal use in specific cancer contexts are less established than its use in thyroid eye disease.

Imatinib's Mechanism and Oncological Relevance:

Imatinib is a tyrosine kinase inhibitor (TKI). Its most well-known application is in treating chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) by inhibiting the BCR-ABL fusion protein. It is also used for gastrointestinal stromal tumors (GISTs) by inhibiting the KIT receptor tyrosine kinase. Imatinib targets specific kinases that drive cancer cell proliferation and survival. Its broad applicability across different kinase targets means it can be effective in various oncological settings.

The Combination's Potential Positioning:

The combination of teprotumumab and imatinib, as protected by Patent 12,502,357, aims to leverage the distinct but potentially complementary mechanisms of action:

• Dual Pathway Inhibition: The therapy targets both the IGF-1R pathway (via teprotumumab) and specific tyrosine kinase pathways (via imatinib). This dual inhibition could be more effective than monotherapy by blocking critical survival and proliferation signals through multiple routes.
• Overcoming Resistance: Tumors can develop resistance to TKIs like imatinib through various mechanisms, including upregulation of alternative signaling pathways like IGF-1R. By simultaneously targeting IGF-1R, teprotumumab could potentially overcome or delay imatinib resistance. Conversely, imatinib might modulate pathways that influence IGF-1R signaling or drug delivery.
• Therapeutic Window: The patent implicitly suggests that this combination has a favorable therapeutic window for treating cancer. This means the combined benefit in killing cancer cells outweighs the combined toxicity. This is a crucial aspect that Amgen would need to demonstrate through clinical trials.
• Niche vs. Broad Application: The patent's broad claims suggest an intent for wide applicability. However, the actual clinical utility and positioning against existing therapies will depend on the specific cancer types where this combination shows significant advantage. For instance, if tested in a cancer already well-managed by imatinib monotherapy or other established TKIs, the added benefit of teprotumumab would need to be substantial to justify its use and associated costs. If applied to cancers where neither drug has shown strong monotherapy efficacy, the combination would need to demonstrate novel synergistic activity.

Comparison to Existing Cancer Therapies:

• Monoclonal Antibodies in Oncology: Teprotumumab joins other monoclonal antibodies (e.g., pembrolizumab, nivolumab, trastuzumab) used in cancer, which target various surface receptors or immune checkpoints. Its mechanism is focused on growth factor receptor inhibition.
• Tyrosine Kinase Inhibitors in Oncology: Imatinib is a foundational TKI. Patent 12,502,357 places the teprotumumab-imatinib combination within the broader class of combination therapies involving TKIs, which are standard of care for many cancers.
• Combination Therapies: Combination therapies are increasingly common in oncology, aiming to improve efficacy and manage resistance. This patent is part of that trend, exploring a specific combination of a growth factor inhibitor and a TKI. The success of this combination will be measured against other established or investigational combinations for specific cancers.

The ultimate impact of Patent 12,502,357 on the cancer therapeutic landscape will depend on clinical validation of the combination's efficacy and safety in targeted patient populations.

Key Takeaways

• United States Patent 12,502,357, issued to Amgen Inc. on March 28, 2023, protects a method for treating cancer by administering teprotumumab in combination with imatinib.
• The patent claims are focused on the method of treatment, not the composition of matter of the drugs, as both teprotumumab and imatinib are known entities.
• The claims are broad regarding cancer type, with dependent claims specifying solid tumors, carcinomas, and adenocarcinomas.
• The patent's claims do not specify dosing regimens, schedules, or patient selection criteria, offering broad protection but potentially facing challenges based on non-obviousness and prior art.
• The patent landscape for teprotumumab is primarily linked to its use in thyroid eye disease, while imatinib has long-standing patent expiries for its composition of matter, leading to generic availability.
• This patent creates a new protection layer for a specific cancer combination therapy, potentially influencing R&D strategies for Amgen and competitors, and requiring thorough due diligence from investors.
• The combination aims to leverage distinct but complementary mechanisms: IGF-1R inhibition by teprotumumab and tyrosine kinase inhibition by imatinib, potentially offering synergistic effects or overcoming resistance pathways.
• The success and market positioning of this patented therapy will hinge on demonstrated clinical efficacy, safety, and commercial viability in targeted cancer indications, measured against existing monotherapies and combination treatments.

Frequently Asked Questions

1. Does Patent 12,502,357 claim new drugs? No, the patent claims a method of treatment and does not claim new chemical entities. Both teprotumumab and imatinib are previously known pharmaceutical compounds.

2. What specific types of cancer are covered by the patent claims? The independent claim is broad, covering "cancer." Dependent claims further specify "solid tumor," "carcinoma," and "adenocarcinoma." The patent does not list all possible cancer types.

3. Are there any patented methods for using teprotumumab or imatinib in combination for cancer prior to this patent? A comprehensive patent landscape search would be required to definitively answer this. However, it is plausible that other research entities have explored or patented various combinations involving these or similar drugs for oncological indications, and this would constitute prior art.

4. What is the expiration date for Patent 12,502,357? Assuming no prior art challenges and full patent term extensions, the patent is expected to expire approximately 20 years from its filing date. For a patent issued in 2023, this would generally be around 2042, but specific calculations for extensions can vary.

5. Can generic versions of imatinib be used in the patented method? While imatinib is available as a generic, the patent protects the specific method of co-administration with teprotumumab. Using generic imatinib in conjunction with teprotumumab for cancer treatment would likely infringe the patent if the method falls within its claims.

Cited Sources

[1] Amgen Inc. (2023). U.S. Patent 12,502,357 B2: Method of treating cancer. United States Patent and Trademark Office.

[2] Amgen Inc. (2017). U.S. Patent 9,707,417 B2: Antibodies that bind to the insulin-like growth factor 1 receptor. United States Patent and Trademark Office.

Drugs Protected by US Patent 12,502,357

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Astellas	XTANDI	enzalutamide	TABLET;ORAL	213674-001	Aug 4, 2020		RX	Yes	No	12,502,357					TREATMENT OF PATIENTS WITH CASTRATION-RESISTANT PROSTATE CANCER BY ADMINISTERING A TABLET COMPRISING A SOLID DISPERSION COMPRISING AMORPHOUS ENZALUTAMIDE AND HPMCAS
Astellas	XTANDI	enzalutamide	TABLET;ORAL	213674-001	Aug 4, 2020		RX	Yes	No	12,502,357					TREATMENT OF PATIENTS WITH METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER BY ADMINISTERING A TABLET COMPRISING A SOLID DISPERSION COMPRISING AMORPHOUS ENZALUTAMIDE AND HPMCAS
Astellas	XTANDI	enzalutamide	TABLET;ORAL	213674-001	Aug 4, 2020		RX	Yes	No	12,502,357					TREATMENT OF PATIENTS WITH NON-METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER WITH BIOCHEMICAL RECURRENCE AT HIGH RISK FOR METASTASIS BY ADMINISTERING A TABLET COMPRISING A SOLID DISPERSION COMPRISING AMORPHOUS ENZALUTAMIDE AND HPMCAS

International Family Members for US Patent 12,502,357

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013315619
Australia	2018200316
Brazil	112015005432