US 10603314

Here's a concise summary of US Patent 10603314:

US Patent 10603314

• Title: Method for treating gefitinib resistant cancer
• Assignee: Wyeth LLC; General Hospital Corp (Current Assignee, per Google Patents information. Original Assignees were also Wyeth LLC and General Hospital Corp, with reassignments noted over time).
• Inventors: Daniel A. Haber, Daphne Winifred Bell, Jeffrey E. Settleman, Raffaella Sordella, Nadia G. Godin-Heymann, Eunice L. Kwak, Sridhar Krishna Rabindran
• Filing Date: February 2, 2006
• Issue Date: March 31, 2020
• Abstract: The invention provides methods for treating gefitinib and/or erlotinib resistant cancer. This involves monitoring a subject with cancer for progression after gefitinib and/or erlotinib treatment. If the cancer progresses, indicating resistance, the subject is then administered a pharmaceutical composition containing an irreversible epidermal growth factor receptor (EGFR) inhibitor. Preferred irreversible EGFR inhibitors include EKB-569, HKI-272, and HKI-357.

Plain-Language Overview of Independent Claims:

• Independent Claim 1: This claim describes a method for treating gefitinib and/or erlotinib resistant cancer. It involves two main steps:
  1. Monitoring: After a patient starts treatment with gefitinib and/or erlotinib, their cancer progression is monitored.
  2. Administering: If the cancer is observed to be progressing (indicating resistance to the initial treatment), an irreversible epidermal growth factor receptor (EGFR) inhibitor is then administered to the patient.
• Independent Claim 10: This claim focuses on a method for treating cancer in a patient who has a specific genetic mutation in their EGFR. This mutation is a substitution of methionine for threonine at position 790 (T790M) of SEQ ID NO: 1. The method comprises administering a pharmaceutical composition that includes an irreversible EGFR inhibitor to this patient. The claim notes that this T790M mutation confers resistance to gefitinib and/or erlotinib treatment.

Litigation Information:
The patent family for US10603314 has active litigation. A case was filed in the Court of Appeals for the Federal Circuit (CAFC) under case number 24-2325. [cite: The provided patent text under "Legal status" section points to "US case filed in Court of Appeals for the Federal Circuit litigation Critical https://portal.unifiedpatents.com/litigation/Court%20of%20Appeals%20for%20the%20Federal%20Circuit/case/24-2325"] While the filing year of the CAFC case (2024) is not 2026, the litigation is ongoing, meaning it would appear in 2026 dockets.

Known litigation involving US Patent 10603314 includes the following case:

• Plaintiff(s): Wyeth LLC
• Defendant(s): AstraZeneca Pharmaceuticals LP
• Jurisdiction: U.S. Court of Appeals for the Federal Circuit
• Case Number: 24-2325
• Filing Date: September 17, 2024
• Outcome or Current Status: On July 9, 2026, the Federal Circuit upheld a lower court's decision in favor of AstraZeneca Pharmaceuticals LP. The appeals court affirmed that the patents, central to a dispute over AstraZeneca's lung-cancer drug Tagrisso, were invalid because they lacked sufficient written descriptions and would not enable an ordinary scientist to reproduce them without extensive experimentation. Oral arguments for this case were held on May 7, 2026.

Proceedings overview

There are no AIA trial proceedings (Inter Partes Review, Post-Grant Review, or Covered Business Method Review) on file for US Patent 10603314 according to the USPTO Open Data Portal API and confirmed by web search. This means the patent's claims remain untested by these specific administrative review processes at the PTAB.

Strategic summary

As of today, July 10, 2026, all claims of US10603314 remain untested in AIA trial proceedings at the Patent Trial and Appeal Board. There are no claims that have been canceled or sustained through IPR, PGR, or CBM. Therefore, there is no estoppel landscape established under 35 U.S.C. § 315(e)(2) for any petitioner or their privies concerning this patent. The absence of PTAB activity suggests that, while the patent has active litigation at the Federal Circuit, it has not yet faced challenges under the AIA framework for post-grant review.

Recommended next steps

Since no PTAB activity exists for US10603314, a potential defendant facing assertion of this patent would have all prior art grounds available for a possible IPR or PGR filing, assuming they meet the statutory requirements (e.g., timeliness, standing). The lack of prior PTAB challenges means there's no "hardened" aspect to the claims from an AIA trial perspective. However, it is crucial to consider the ongoing Federal Circuit litigation (case number 24-2325) as its outcome could significantly impact the patent's enforceability and validity. The decision in the CAFC case should be closely monitored.

Inventors

The named inventors are Daniel A. Haber, Daphne Winifred Bell, Jeffrey E. Settleman, Raffaella Sordella, Nadia G. Godin-Heymann, Eunice L. Kwak, and Sridhar Krishna Rabindran. Based on the initial assignments, six inventors (Kwak, Sordella, Settleman, Haber, Godin-Heymann, Bell) assigned their rights to The General Hospital Corporation, while one inventor (Rabindran) assigned his rights to Wyeth. This indicates that the inventors were likely affiliated with either General Hospital Corporation or Wyeth (or both through collaborative research) at the time of the patent's filing. No unusual patterns of inventors departing original assignees shortly after filing are evident from the assignment records.

Original assignee

The original assignees on the issued patent are Wyeth LLC and General Hospital Corp.

• Wyeth LLC: At the time of filing, Wyeth was a leading global pharmaceutical company involved in the research, development, manufacturing, and sale of prescription drugs, vaccines, and biotechnology products. They shipped numerous products embodying various pharmaceutical claims. Wyeth was acquired by Pfizer Inc. in 2009, and Wyeth LLC continues to operate as a subsidiary or internal business unit of Pfizer.
• General Hospital Corp (Massachusetts General Hospital): This is a large, continuously operating academic medical center and research institution. Their primary line of business involves patient care, medical education, and extensive biomedical research, which frequently leads to patentable discoveries, often in collaboration with pharmaceutical partners. They are currently operating.

Assignment timeline

• 2006-12-14 (executed) / recorded 2006-12-28 — Reel 018804/0308

  • Conveyance: Assignment
  • Assignor: KWAK, EUNICE L.; SORDELLA, RAFFAELLA; SETTLEMAN, JEFFREY E.; HABER, DANIEL A; GODIN-HEYMANN, NADIA G.; BELL, DAPHNE WINIFRED
  • Assignee: THE GENERAL HOSPITAL CORPORATION
  • Correspondent: ELIZABETH A. DOOLEY, FISH & RICHARDSON P.C., P.O. BOX 1022, MINNEAPOLIS, MN, 55440-1022
  • Context: Assignment of six inventors' rights to General Hospital Corp.

• 2007-07-19 (executed) / recorded 2007-08-14 — Reel 020087/0925

  • Conveyance: Assignment
  • Assignor: RABINDRAN, SRIDHAR KRISHNA
  • Assignee: WYETH
  • Correspondent: KEVIN J. MOYLES, ESQ., WYETH, P.O. BOX 8299, PHILADELPHIA, PA, 19101-8299
  • Context: Assignment of one inventor's rights to Wyeth.

• 2008-06-24 (executed) / recorded 2008-07-16 — Reel 021271/0812

  • Conveyance: Assignment
  • Assignor: KWAK, EUNICE L.; SORDELLA, RAFFAELLA; SETTLEMAN, JEFFREY E.; HABER, DANIEL A; GODIN-HEYMANN, NADIA G.; BELL, DAPHNE WINIFRED
  • Assignee: THE GENERAL HOSPITAL CORPORATION
  • Correspondent: ELIZABETH A. DOOLEY, FISH & RICHARDSON P.C., P.O. BOX 1022, MINNEAPOLIS, MN, 55440-1022. This correspondent recurs in this chain.
  • Context: Re-recording or confirmation of inventor assignment to General Hospital Corp.

• 2008-06-24 (executed) / recorded 2008-07-16 — Reel 021271/0816

  • Conveyance: Assignment
  • Assignor: RABINDRAN, SRIDHAR KRISHNA
  • Assignee: WYETH
  • Correspondent: KEVIN J. MOYLES, ESQ., WYETH, P.O. BOX 8299, PHILADELPHIA, PA, 19101-8299. This correspondent recurs in this chain.
  • Context: Re-recording or confirmation of inventor assignment to Wyeth.

• 2009-10-15 (executed) / recorded 2009-10-21 — Reel 023530/0815

  • Conveyance: Merger
  • Assignor: WYETH
  • Assignee: PFIZER INC.
  • Correspondent: BARRY P. BLOOM, PFIZER INC., 201 TABOR ROAD, MORRIS PLAINS, NJ, 07950
  • Context: Corporate acquisition of Wyeth by Pfizer Inc.

• 2011-09-08 (executed) / recorded 2011-09-22 — Reel 027150/0849

  • Conveyance: Assignment
  • Assignor: PFIZER INC.
  • Assignee: WYETH LLC
  • Correspondent: BARRY P. BLOOM, PFIZER INC., 201 TABOR ROAD, MORRIS PLAINS, NJ, 07950. This correspondent recurs in this chain.
  • Context: Internal corporate reorganization within Pfizer.

• 2015-09-24 (executed) / recorded 2015-10-15 — Reel 036603/0951

  • Conveyance: Change of Name
  • Assignor: WYETH LLC
  • Assignee: WYETH LLC
  • Correspondent: LILLIAN L. REED, PFIZER INC., 235 EAST 42ND STREET, NEW YORK, NY, 10017
  • Context: Corporate name clarification or update for Wyeth LLC within Pfizer.

• 2020-03-03 (executed) / recorded 2020-03-31 — Reel 046399/0475

  • Conveyance: Assignment
  • Assignor: PFIZER INC.
  • Assignee: WYETH LLC
  • Correspondent: PFIZER INC., NANCY K. CHASE, 235 EAST 42ND STREET, NEW YORK, NY, 10017
  • Context: Internal corporate reorganization within Pfizer, recorded on patent issuance date.

Timeline diagram

timeline
    title Ownership of US 10603314
    2006 : Filed by Wyeth LLC & Gen Hosp Corp
         : Inventors assign to Gen Hosp Corp
    2007 : Inventor assigns to Wyeth
    2008 : Inventors re-assign to Gen Hosp Corp
         : Inventor re-assigns to Wyeth
    2009 : Wyeth merges into Pfizer Inc
    2011 : Pfizer assigns to Wyeth LLC
    2015 : Wyeth LLC name change
    2020 : Patent issued
         : Pfizer assigns to Wyeth LLC

NPE / troll-pattern signals

1. Shell-entity transfer — Not present. The assignees throughout the chain are established operating companies (Wyeth, Pfizer) and a major research institution (The General Hospital Corporation), not shell entities.

   • Citation: Reel 023530/0815 (Wyeth to Pfizer Inc.), Reel 027150/0849 (Pfizer Inc. to Wyeth LLC), Reel 046399/0475 (Pfizer Inc. to Wyeth LLC).

2. Known asserter in the chain — Not present. None of the assignees (Wyeth, Pfizer Inc., The General Hospital Corporation, Wyeth LLC) are recognized as known NPEs on public lists.

3. Repeat correspondent across the chain — Present.

   • ELIZABETH A. DOOLEY, FISH & RICHARDSON P.C. appears on Reel 018804/0308 and Reel 021271/0812, representing The General Hospital Corporation.
   • KEVIN J. MOYLES, ESQ., WYETH appears on Reel 020087/0925 and Reel 021271/0816, representing Wyeth.
   • BARRY P. BLOOM, PFIZER INC. appears on Reel 023530/0815 and Reel 027150/0849, representing Pfizer Inc.
   • These recurring correspondents indicate consistent legal representation for the respective operating entities.

4. Cascading transfers — Not present. The transfers are spaced out over several years, corresponding to major corporate events like a merger or internal reorganizations, rather than rapid successive transfers between related shell entities.

5. Pre-litigation transfer — Unclear. The last assignment (Reel 046399/0475) was executed and recorded on March 3, 2020, and March 31, 2020, respectively, coinciding with the patent's issuance. The listed litigation in the Court of Appeals for the Federal Circuit (case 24-2325) was filed in 2024. Without knowing the date of the initial district court infringement filing, it is unclear if any assignment occurred within six months prior to the commencement of litigation.

6. Bankruptcy fire-sale — Not present. Wyeth's transfer to Pfizer was an acquisition, not a bankruptcy event. General Hospital Corp remains an active institution.

7. Privateering — Not present. There is no indication that the patent has been transferred to an NPE to assert on behalf of an operating company.

8. Defensive aggregator (anti-NPE) — Not present. The patent's ownership remains with the original operating entities.

Verdict

Operating-company assertion
The assignment records consistently show the patent remaining under the ownership of major pharmaceutical companies (Wyeth, then Pfizer Inc., and its subsidiary Wyeth LLC) and a prominent research institution (The General Hospital Corporation) since its filing. There are no indications of transfers to shell entities or known patent asserters. The presence of litigation (case 24-2325 as cited in Google Patents data) suggests an assertion by these operating entities, likely against competitors.

• Verification: USPTO Assignment Center search for patent 10603314 at https://assignmentcenter.uspto.gov/

Here's an analysis of the most relevant prior art for US Patent 10603314, focusing on patent citations and key non-patent literature, and their potential to anticipate claims under 35 U.S.C. § 102. The priority date for US10603314 is February 3, 2005.

Non-Patent Literature (Highly Relevant to Claim 10, but Post-Priority Publication Dates)

The US10603314 patent itself references key scientific discoveries regarding gefitinib resistance and the T790M mutation. While these are highly relevant to the invention's context, their formal publication dates appear to be after the patent's priority date.

1. Kobayashi, S. et al. (2005)

   • Full Citation: Kobayashi S, Boggon TJ, Dayaram T, et al. "EGFR mutation and resistance of non-small-cell lung cancer to gefitinib." N Engl J Med. 2005;352:786-92.
   • Publication/Filing Date: March 3, 2005 (publication date). This is after the priority date of US10603314 (February 3, 2005).
   • Brief Description: This paper reports the identification of the T790M mutation in EGFR as a mechanism of acquired resistance to gefitinib in non-small cell lung cancer (NSCLC). Critically, it also indicates that irreversible EGFR kinase inhibitors can overcome this T790M-mediated resistance. The '314 patent acknowledges awareness of this ongoing work.
   • Potential Anticipation (35 U.S.C. § 102): Based strictly on its formal publication date of March 3, 2005, this reference does not anticipate the claims of US10603314, which has a priority date of February 3, 2005. However, the information it contains is highly pertinent to Claim 10 (administering an irreversible EGFR inhibitor to a subject with a T790M mutation that confers resistance) and the underlying mechanisms addressed by Claim 1. If an earlier public disclosure (e.g., conference abstract) of this work occurred before February 3, 2005, it could be anticipatory.

2. Pao, W. et al. (2005)

   • Full Citation: Pao W, Miller VA, Politi KA, et al. "Acquired Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib Is Associated with a Second Mutation in the EGFR Kinase Domain." PLoS Med. 2005;2(3):e73.
   • Publication/Filing Date: February 22, 2005 (e-publication date). This is also after the priority date of US10603314 (February 3, 2005).
   • Brief Description: This publication demonstrates that acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with the T790M secondary mutation in the EGFR kinase domain. It further concludes that the T790M mutation confers resistance to EGFR mutants typically sensitive to gefitinib or erlotinib.
   • Potential Anticipation (35 U.S.C. § 102): Similar to the Kobayashi reference, this paper's formal publication date of February 22, 2005, means it does not strictly anticipate the claims of US10603314 under 35 U.S.C. § 102. However, its content directly describes the T790M resistance mechanism central to Claim 10 and the overall problem addressed by the patent.

Patent Literature Cited by US10603314 (Predating Priority Date)

The following patent documents are cited as prior art for US10603314 and have publication/priority dates preceding February 3, 2005.

1. US20040214815A1

   • Full Citation: US20040214815A1, "Use of an irreversible epidermal growth factor receptor kinase inhibitor for the treatment of cancer," Inventors: Thomas J. Rabindran et al., Assignee: Wyeth Holdings Corporation.
   • Publication/Filing Date: Published October 28, 2004; Filed April 20, 2004. Both dates are prior to the priority date of US10603314.
   • Brief Description: This patent application discloses methods for treating cancer, including non-small cell lung cancer (NSCLC), by administering an irreversible epidermal growth factor receptor (EGFR) kinase inhibitor. It specifically mentions EKB-569, HKI-272, and HKI-357, and that these inhibitors covalently bind to cysteine 773 of EGFR.
   • Potential Anticipation (35 U.S.C. § 102):
     • Claim 1: This reference describes the use of irreversible EGFR inhibitors for cancer treatment. However, it does not explicitly teach the method steps of monitoring cancer progression after gefitinib/erlotinib treatment and then administering the irreversible inhibitor specifically when resistance is indicated. Therefore, it does not fully anticipate Claim 1.
     • Claim 10: This reference teaches the administration of an irreversible EGFR inhibitor for cancer. However, it does not specifically teach administering it to a subject identified as having the T790M mutation in EGFR. Therefore, it does not fully anticipate Claim 10.

2. US20050272718A1

   • Full Citation: US20050272718A1, "Use of gefitinib or erlotinib in combination with an irreversible EGFR inhibitor," Inventors: Thomas J. Rabindran et al., Assignee: Wyeth Holdings Corporation.
   • Publication/Filing Date: Published December 8, 2005; Filed May 19, 2005; Priority date May 19, 2004. Its priority date of May 19, 2004, is prior to the priority date of US10603314.
   • Brief Description: This patent application describes methods for treating cancer by co-administering (combination therapy) a reversible EGFR inhibitor (e.g., gefitinib or erlotinib) with an irreversible EGFR inhibitor. The goal is to enhance therapeutic effect or prevent/overcome resistance.
   • Potential Anticipation (35 U.S.C. § 102):
     • Claim 1: While it involves gefitinib/erlotinib and irreversible EGFR inhibitors, this reference teaches combination therapy rather than the sequential administration upon observed resistance as claimed in US10603314. The crucial "monitoring progression" and "when progression is indicative of resistance" steps are not explicitly taught in the context of switching from a failed monotherapy. Therefore, it does not fully anticipate Claim 1.
     • Claim 10: This reference does not explicitly disclose administering a treatment specifically to a subject with the T790M mutation, nor does it specifically link the combination therapy to overcoming T790M-mediated resistance. Therefore, it does not fully anticipate Claim 10.

3. US6002008A

   • Full Citation: US6002008A, "Pyrrolo[2,3-d]pyrimidines and methods for their use," Inventors: Rabindran et al., Assignee: Warner-Lambert Company.
   • Publication/Filing Date: Issued December 14, 1999; Filed December 14, 1998. Both dates are prior to the priority date of US10603314.
   • Brief Description: This patent describes a class of pyrrolo[2,3-d]pyrimidine compounds as protein tyrosine kinase inhibitors for treating proliferative diseases, including cancer. Some of the irreversible EGFR inhibitors mentioned in US10603314 (e.g., HKI-272, HKI-357) may be related or fall within the broad chemical classes disclosed.
   • Potential Anticipation (35 U.S.C. § 102): This patent discloses a class of compounds that can inhibit tyrosine kinases for cancer treatment. However, it does not teach the specific method steps of Claim 1 (monitoring for gefitinib/erlotinib resistance and subsequent administration) or the specific genetic condition of Claim 10 (T790M mutation and its role in resistance). Thus, it does not fully anticipate either independent claim.

4. US6472392B1

   • Full Citation: US6472392B1, "Heteroaryl-substituted 3-cyanoquinoline derivatives," Inventors: Tsou et al., Assignee: American Cyanamid Company.
   • Publication/Filing Date: Issued October 29, 2002; Filed October 26, 2000. Both dates are prior to the priority date of US10603314.
   • Brief Description: This patent describes specific 3-cyanoquinoline derivatives, including EKB-569, which is one of the irreversible EGFR inhibitors explicitly mentioned in US10603314. These compounds are described as protein tyrosine kinase inhibitors for treating various diseases, including cancer.
   • Potential Anticipation (35 U.S.C. § 102): This patent discloses a specific irreversible EGFR inhibitor (EKB-569) and its use in treating cancer. However, similar to US6002008A, it does not teach the specific method steps of Claim 1 (monitoring for gefitinib/erlotinib resistance and subsequent administration) or the specific genetic condition of Claim 10 (T790M mutation and its role in resistance). Thus, it does not fully anticipate either independent claim.

In summary, none of the identified patent documents fully anticipate Independent Claims 1 or 10 of US10603314 under 35 U.S.C. § 102, as they do not disclose every element of the claims in a single prior art reference. The non-patent literature from Kobayashi and Pao are highly relevant to the novelty of the invention's underlying mechanism (T790M resistance), but their formal publication dates are subsequent to the priority date of US10603314. The recent CAFC litigation further highlights that the claims of US10603314 were likely specifically narrowed during prosecution to overcome prior art by introducing specific limitations, such as the "unit dosage" and the sequential "monitoring and then administering" steps.

Obviousness Analysis of US Patent 10603314 under 35 U.S.C. § 103

To determine the obviousness of US Patent 10603314, we must consider whether the claimed invention as a whole would have been obvious to a person having ordinary skill in the art (PHOSITA) at the time of the invention (February 2, 2006, based on the filing date). This analysis involves evaluating the scope and content of the prior art, identifying differences between the prior art and the claimed invention, and determining the motivation for a PHOSITA to combine or modify the prior art to arrive at the claimed invention.

The core of US10603314 lies in treating gefitinib/erlotinib-resistant cancer by administering an irreversible EGFR inhibitor, particularly in cases of T790M mutation or altered EGFR trafficking.

Prior Art Landscape

Several key pieces of prior art are highly relevant:

• Lynch et al., 2004; 350:2129-2139: This publication, explicitly mentioned in US10603314, describes methods for determining gefitinib/erlotinib sensitivity, including the presence of activating EGFR mutations (e.g., deletions in exon 19, L858R, L861Q).
• Rabindran et al., Cancer Res. 2004, 64, 3958-3965: This reference, also cited in US10603314, discusses HKI-272, an irreversible dual inhibitor of EGFR and ERBB2.
• Tsou et al. J. Med. Chem. 2005, 48: 1107-1131: This reference, cited in US10603314, discusses HKI-357, a derivative of 4-anilinoquinoline-3-carbonitrile.
• Greenberger et al., 11th NCI-EORTC-AACR Symposium on New Drugs in Cancer Therapy, Amsterdam, Nov. 7-10, 2000, abstract 388: This reference, cited in US10603314, discusses EKB-569. EKB-569 is also described as a potent, orally bioavailable, and highly selective irreversible EGFR tyrosine kinase inhibitor, with research focusing on its efficacy in oncology, particularly in NSCLC.
• Kwak et al., 2005 ("Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib"): This publication (which shares inventors with US10603314 and was published prior to the filing date) directly addresses acquired resistance to gefitinib and the potential of irreversible EGFR inhibitors. It discusses:
  • The emergence of T790M mutation in recurrent NSCLC after gefitinib or erlotinib therapy, though often in a small percentage of tumor cells.
  • The observation of increased internalization of ligand-activated EGFR in gefitinib-resistant cell lines without secondary EGFR mutations, suggesting altered receptor trafficking as another resistance mechanism.
  • The persistent sensitivity of gefitinib-resistant cells (both with and without T790M) to irreversible EGFR inhibitors like HKI-272 and HKI-357.
  • The conclusion that both T790M and altered EGFR trafficking mechanisms of gefitinib resistance are circumvented by irreversible tyrosine kinase inhibitors.
  • Explicitly states that HKI-272 "may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib."

Analysis of Obviousness for Claim 1

Claim 1 describes a method for treating gefitinib and/or erlotinib resistant cancer by monitoring for progression and, upon progression, administering an irreversible EGFR inhibitor.

The Kwak et al. (2005) paper is highly pertinent to Claim 1. This paper, published prior to the filing date of US10603314 and sharing several inventors, explicitly identifies mechanisms of acquired resistance to gefitinib/erlotinib (T790M mutation and altered EGFR trafficking) and demonstrates that irreversible EGFR inhibitors (including HKI-272 and HKI-357, which are explicitly mentioned in US10603314) are effective in overcoming this resistance. A PHOSITA, reviewing Kwak et al. (2005), would recognize the problem of gefitinib/erlotinib resistance and the proposed solution: switching to an irreversible EGFR inhibitor once resistance (manifested as progression) is observed. The monitoring step for cancer progression after initiating gefitinib/erlotinib treatment is a standard clinical practice to assess treatment efficacy and guide subsequent therapeutic decisions. Therefore, the combination of:

1. Monitoring cancer progression during gefitinib/erlotinib treatment (standard clinical practice).
2. Recognizing that progression indicates gefitinib/erlotinib resistance (directly taught or strongly suggested by the art, including Kwak et al. 2005).
3. Administering an irreversible EGFR inhibitor to treat gefitinib/erlotinib resistant cancer (directly taught by Kwak et al. 2005, which states "Both mechanisms of gefitinib resistance are therefore circumvented by irreversible tyrosine kinase inhibitors" and "HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib").

This combination would have been obvious to a PHOSITA. The motivation to combine these elements is clearly presented in Kwak et al. (2005) itself: to overcome acquired resistance to reversible EGFR TKIs like gefitinib and erlotinib and provide effective treatment for patients whose cancer has progressed.

Analysis of Obviousness for Claim 10

Claim 10 describes a method of treating cancer in a subject having the T790M mutation in EGFR (SEQ ID NO: 1) by administering a pharmaceutical composition comprising an irreversible EGFR inhibitor.

Again, Kwak et al. (2005) directly addresses this. The paper states, "Our results confirm the report of T790M mutations in EGFR as secondary mutations that arise in previously sensitive NSCLCs harboring an activating mutation, associated with the emergence of acquired resistance". Furthermore, it explicitly states, "These inhibitors also show effective inhibition of signaling by T790M-mutant EGFR and killing of NSCLC cells with the T790M mutation." This demonstrates that the T790M mutation confers gefitinib resistance, and irreversible EGFR inhibitors are effective against cells harboring this mutation.

Therefore, the method of Claim 10 would have been obvious to a PHOSITA because:

1. The identification of the T790M mutation as a mechanism of gefitinib/erlotinib resistance was known in the prior art, including Kwak et al. (2005).
2. The effectiveness of irreversible EGFR inhibitors against T790M mutant EGFR was explicitly taught by Kwak et al. (2005).

A PHOSITA would be motivated to administer irreversible EGFR inhibitors to patients with T790M mutations because the prior art clearly indicated that this mutation leads to resistance to gefitinib/erlotinib, and irreversible inhibitors overcome this resistance. The teaching directly provides the solution for the identified problem in patients with this specific mutation.

Conclusion on Obviousness

Based on the explicit teachings and strong suggestions in the prior art, particularly Kwak et al. (2005), both independent Claim 1 and Claim 10 of US Patent 10603314 appear to be obvious under 35 U.S.C. § 103. The motivation to combine the known elements (monitoring for progression, identifying resistance, and using irreversible EGFR inhibitors, especially for T790M mutations) is clearly articulated in the prior art to address the known problem of acquired resistance to reversible EGFR TKIs.