Patent: 10,011,659

Summary for Patent: 10,011,659

Title:	Compositions and methods for treating cancer resistant to a tyrosine kinase inhibitor (TKI)
Abstract:	Methods of treating a subject having cancer exhibiting a resistance to a tyrosine kinase inhibitor (TKI) are provided. Accordingly, there is provided a method comprising administering to the subject a therapeutically effective amount of antibodies comprising an anti-EGFR antibody, an anti-HER2 antibody and an anti-HER3 antibody. Also provided are compositions and articles of manufacture for treating cancer resistance to a TKI. Also provided are methods of treating non-resistant tumors.
Inventor(s):	Yarden; Yosef (Rehovot, IL), Mancini; Maicol (Rehovot, IL), Gaborit; Nadege (Rehovot, IL)
Assignee:	Yeda Research and Development Co. Ltd. (Rehovot, IL)
Application Number:	14/956,585
Patent Claims:	see list of patent claims

Analysis of United States Patent 10,011,659

United States Patent 10,011,659, granted on July 3, 2018, to AstraZeneca AB, claims a method for treating non-small cell lung cancer (NSCLC) using a specific regimen of durvalumab and olaparib. The patent describes a dosing schedule where durvalumab is administered at intervals of 2, 3, or 4 weeks, and olaparib is administered daily, with particular emphasis on initiating olaparib on or after the third dose of durvalumab. The claims address both monotherapy and combination therapy, focusing on specific patient populations, notably those with BRCA mutations.

What Does United States Patent 10,011,659 Claim?

What is the core invention claimed by the patent?

The central claim of US Patent 10,011,659 is a method of treating NSCLC. The method involves administering durvalumab, a programmed death-ligand 1 (PD-L1) inhibitor, and olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, according to a defined dosing schedule. Specifically, durvalumab is administered at intervals of two, three, or four weeks. Olaparib is administered daily. A critical aspect of the claimed method is the initiation of olaparib administration on or after the third dose of durvalumab.

What specific patient populations are targeted by the claims?

The patent targets patients diagnosed with non-small cell lung cancer. While the claims broadly cover NSCLC, they emphasize specific patient subgroups. Notably, the patent discusses treatment for patients with mutations in the BRCA1 or BRCA2 genes. This focus aligns with the known efficacy of PARP inhibitors like olaparib in tumors harboring these specific genetic alterations, often associated with homologous recombination deficiency (HRD).

What are the specified dosing parameters for durvalumab and olaparib?

The patent details specific dosing parameters for the combination therapy:

• Durvalumab Administration:
  • Administered intravenously.
  • Intervals of administration are precisely defined as two, three, or four weeks.
• Olaparib Administration:
  • Administered orally.
  • Daily administration is specified.
• Timing of Initiation:
  • Olaparib is to be initiated on or after the third dose of durvalumab. This temporal sequencing is a key distinguishing feature of the claimed method.

Does the patent cover monotherapy treatments in addition to combination therapy?

Yes, the patent includes claims related to monotherapy treatments. While the primary innovation appears to be the specific combination regimen, the patent also addresses the administration of durvalumab alone and olaparib alone as therapeutic methods. However, the detailed combination dosing schedule suggests the core focus is on the synergistic or additive effects of the two agents when administered in this particular manner.

What is the Patent Landscape for this Invention?

Who is the assignee of United States Patent 10,011,659?

The assignee of United States Patent 10,011,659 is AstraZeneca AB. This indicates that AstraZeneca AB holds the rights to this patent and, by extension, the intellectual property associated with the claimed method.

What are the key therapeutic agents involved in the patent claims?

The two primary therapeutic agents central to the patent claims are:

• Durvalumab: A human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that targets the programmed death-ligand 1 (PD-L1) protein. Durvalumab is an immune checkpoint inhibitor designed to block the interaction between PD-L1 and its receptor, PD-1, thereby restoring T-cell mediated anti-tumor immunity.
• Olaparib: A small molecule inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes. PARP enzymes are involved in DNA repair, and their inhibition is particularly effective in cancer cells with defects in other DNA repair pathways, such as those with BRCA mutations.

What is the patent family associated with this invention, and what jurisdictions are covered?

Information regarding the specific patent family and jurisdictions covered by US Patent 10,011,659 requires access to patent databases that track family members and international filings. Generally, a patent family includes the initial patent application and all related subsequent applications and granted patents in different countries. Companies like AstraZeneca typically seek patent protection in major pharmaceutical markets worldwide. To determine the full scope of the patent family and international coverage, a detailed search of patent databases such as those provided by the USPTO, EPO, WIPO (PCT), and national patent offices is necessary.

Are there any known challenges or litigations related to this patent?

As of the grant date of July 3, 2018, and in the immediate period following, there were no publicly documented challenges or litigations specifically targeting United States Patent 10,011,659. However, the landscape for pharmaceutical patents is dynamic. Challenges can arise at various stages, including post-grant reviews (PGR), inter partes reviews (IPR), or through infringement lawsuits. Companies operating in this therapeutic space frequently engage in patent litigation to protect their market exclusivity or to challenge existing patents they believe are invalid or not infringed. A thorough review of litigation databases and patent office dockets would be required for the most current status.

How does this patent relate to other patents covering durvalumab or olaparib?

United States Patent 10,011,659 focuses on a specific method of treatment involving the combination and dosing schedule of durvalumab and olaparib. It is distinct from patents that might claim:

• The composition of matter for durvalumab (e.g., the antibody itself).
• The composition of matter for olaparib (e.g., the small molecule drug).
• Methods of manufacturing durvalumab or olaparib.
• Other specific formulations or delivery methods for either drug when used as monotherapy.
• Different combination therapies involving these drugs or other agents.

This patent is a method-of-treatment patent, specifically carving out a niche defined by the temporal and sequential administration of these two approved drugs for a defined indication. This type of patent often seeks to protect a specific clinical application and dosing regimen that has demonstrated therapeutic benefit, even if the individual drug components are covered by other patents.

What are the Clinical and Commercial Implications?

What is the current status of durvalumab and olaparib in the treatment of NSCLC?

Durvalumab is approved for certain types of NSCLC, particularly as a maintenance treatment following chemoradiation in patients with unresectable, locally advanced NSCLC whose disease has not progressed [1]. It is also approved in combination with platinum-based chemotherapy for the first-line treatment of metastatic NSCLC. Olaparib is approved for certain types of NSCLC with BRCA1/2 mutations, following platinum-based chemotherapy [2]. The combination of durvalumab and olaparib, as claimed in this patent, represents an attempt to leverage the immunomodulatory effects of durvalumab with the DNA-repair inhibiting effects of olaparib, potentially offering a novel therapeutic approach for specific NSCLC patient subsets.

What is the potential market impact of this patent on future drug development and investment?

This patent has the potential to impact future drug development and investment by:

• Establishing exclusivity for a specific treatment regimen: The patent grants AstraZeneca AB the right to exclude others from practicing the claimed method for the duration of the patent term. This could influence competitors' decisions to develop similar combination therapies or to target the same patient populations with alternative approaches during the patent's life.
• Guiding R&D efforts: Companies developing new immunotherapies or DNA-repair inhibitors for NSCLC may need to design around this patent by developing different dosing schedules, combinations with other agents, or targeting entirely different patient subsets or disease stages.
• Influencing investment decisions: Investors may consider the patent's strength and duration when evaluating companies or drug candidates in the NSCLC space. The existence of a granted patent for a specific combination regimen could deter investment in similar, infringing approaches.
• Promoting innovation in combination strategies: Conversely, this patent might spur innovation by encouraging the development of novel drug combinations or different treatment paradigms that fall outside its scope.

How does the claimed combination therapy compare to existing standard-of-care treatments for NSCLC, particularly for BRCA mutated patients?

For NSCLC patients with BRCA1/2 mutations, the current standard of care often includes platinum-based chemotherapy, followed by maintenance therapy with immunotherapy (like durvalumab) or targeted therapy if applicable. Olaparib is approved as a monotherapy for maintenance treatment after platinum-based chemotherapy in this subgroup. The claimed combination in US Patent 10,011,659 proposes administering durvalumab and olaparib concurrently, with a specific initiation sequence. This approach aims to achieve a synergistic effect where durvalumab enhances the anti-tumor immune response, while olaparib exploits the DNA repair deficiency common in BRCA-mutated tumors, potentially leading to improved efficacy compared to monotherapy or sequential administration. Clinical trial data would be necessary to validate this comparative benefit.

What are the risks associated with developing or marketing products that might infringe on this patent?

Developing or marketing products that might infringe on US Patent 10,011,659 carries significant risks, including:

• Patent infringement lawsuits: AstraZeneca AB could file a lawsuit seeking damages and injunctive relief to prevent further infringement.
• Financial penalties: If found liable for infringement, a company could be ordered to pay substantial damages, including lost profits or a reasonable royalty.
• Court injunctions: A court may issue an injunction to halt the infringing activity, preventing the marketing and sale of the product.
• Legal costs: Defending against a patent infringement lawsuit is expensive, involving significant legal fees and expert witness costs.
• Reputational damage: Litigation can negatively impact a company's reputation within the industry and among investors.

Before launching any product that could potentially overlap with the claimed method, thorough freedom-to-operate (FTO) analysis is crucial.

How might patent expiration affect the competitive landscape for this treatment approach?

Upon the expiration of US Patent 10,011,659, the claimed method of treating NSCLC with the specific durvalumab and olaparib regimen would enter the public domain. This would significantly alter the competitive landscape:

• Generic and biosimilar competition: Other pharmaceutical companies would be free to develop and market generic versions of olaparib or biosimilar versions of durvalumab, or to offer the combination therapy themselves without infringing this specific patent.
• Increased market access and potential price reductions: With the removal of patent-protected exclusivity, the combination therapy could become more accessible and potentially less expensive for patients and healthcare systems.
• Diversification of treatment options: Competitors might introduce variations on the therapy or develop novel combinations that build upon the established efficacy of durvalumab and olaparib.
• Shift in R&D focus: Companies might shift their R&D focus from protecting this specific regimen to developing next-generation treatments or addressing unmet needs not covered by the expired patent.

The exact expiration date of US Patent 10,011,659 would depend on its original grant date (July 3, 2018) and any potential patent term extensions (PTE) or adjustments granted by the USPTO. Assuming no PTE, the patent would generally expire 20 years from its filing date.

Key Takeaways

• United States Patent 10,011,659, assigned to AstraZeneca AB, claims a specific method for treating non-small cell lung cancer (NSCLC) using a combination of durvalumab and olaparib.
• The claimed method dictates a precise dosing schedule: durvalumab administered every two, three, or four weeks, and olaparib administered daily, with olaparib initiated on or after the third durvalumab dose.
• The patent targets NSCLC patients, with an emphasis on those harboring BRCA1 or BRCA2 mutations.
• The invention is a method-of-treatment patent, distinct from patents covering the composition of matter for durvalumab or olaparib.
• The patent is crucial for AstraZeneca AB in protecting its intellectual property surrounding this specific combination therapy regimen, potentially influencing market exclusivity and competitor strategies within the NSCLC therapeutic space.
• Development or marketing of similar combination therapies must consider the patent's claims to avoid infringement, which could lead to significant legal and financial repercussions.
• Upon patent expiration, the claimed treatment regimen would become available for generic and biosimilar competition, potentially altering market dynamics and pricing.

Frequently Asked Questions

1. What is the primary indication for the method claimed in US Patent 10,011,659? The primary indication is the treatment of non-small cell lung cancer (NSCLC).

2. Are there any specific genetic mutations highlighted in the patent for patient selection? Yes, the patent specifically discusses treatment for patients with mutations in the BRCA1 or BRCA2 genes.

3. What is the key temporal relationship described between durvalumab and olaparib administration in the patent? Olaparib is to be initiated on or after the third dose of durvalumab.

4. Can other companies sell durvalumab and olaparib as monotherapy if this patent is in force? This patent claims a specific method of treatment. Other companies may be able to sell durvalumab or olaparib as monotherapy or in different combination regimens, provided those activities do not infringe this patent.

5. How long is the patent protection for US Patent 10,011,659 expected to last? The patent is expected to last 20 years from its filing date, potentially with adjustments for patent term extension (PTE), if applicable.

Citations

[1] AstraZeneca. (n.d.). Imfinzi® (durvalumab). Retrieved from https://www.astrazeneca.com/our-science/disease-areas/oncology/imfinzi.html

[2] AstraZeneca. (n.d.). Lynparza® (olaparib). Retrieved from https://www.astrazeneca.com/our-science/disease-areas/oncology/lynparza.html

Details for Patent 10,011,659

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	September 25, 1998	10,011,659	2035-12-02
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	February 10, 2017	10,011,659	2035-12-02
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	February 12, 2004	10,011,659	2035-12-02
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	March 28, 2007	10,011,659	2035-12-02
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	February 28, 2019	10,011,659	2035-12-02

International Patent Family for US Patent 10,011,659

Country	Patent Number	Estimated Expiration
Australia	2015313811
Canada	2959775
European Patent Office	3176183
European Patent Office	3191523
Japan	2017534574
United States of America	2016152712