Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Election/Restriction
Applicant elected, without traverse, Group I invention , drawn to a method of treating a subject for KRAS mutant cancer; and (i) sotorasib as the KRAS inhibitor species; (ii) KRAS mutant non-small cell lung cancer (NSCLC) as the KRAS mutant cancer species; (iii) previous treatment with a KRAS inhibitor (claim 12) as the prior cancer therapy species; and (iv) immunotherapy (from claim 25) as the additional cancer therapy species, in the reply filed on 07/31/2026.
Claims 1, 2, 6, 9, 10, 12, 13, 15, 21, 22, 24, 25, 33, 34, and 38 read on the elected invention and species.
Claims 26-28 and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Status of Claims
Claims 1, 2, 6, 9-13, 15, 21, 22, 24-28, 30, 33, 34, and 38 are pending in the instant application.
Claims 26-28 and 30 are withdrawn.
Claims 1, 2, 6, 9-13, 15, 21, 22, 24, 25, 33, 34, and 38 are currently under examination.
Priority
The instant application 18/293,144 filed on January 29, 2024, is 371 of PCT/US2022/074317 filed on July 29, 2022, which claims priority benefit of US provisional application No. 63/227,237 filed on July 29, 2021. Instant Example 2-9 were not disclosed in US provisional application No. 63/227,237.
Information Disclosure Statement
The information disclosure statements filed 06/21/2024, 01/22/2025, 04/14/2025, 07/01/2025, 08/03/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the reference listed in IDS are being considered by the Examiner.
Drawings
The drawings dated 01/29/2024 are objected to under 37 CFR 1.83(a). The drawings are objected to under 37 CFR 1.83(a) because they fail to show Figs 1-9 as described in the specification. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). The Drawings filed on 01/29/2024 are blank. There are no drawings/figures in WO 2023010121 A1 and US 20240374597A1.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because the description of Drawings/Figures 1-9 (See [0022]-[0030]) and Examples ([0114]-[0122]) lack sufficient support due to missing Drawings/Figures.
Claim Objections
Claims 1 and 34 are objected to because of following informalities:
Claim 1 recites “A method of treating a subject for KRAS mutant cancer”, which should read “A method of treating KRAS mutant cancer in a subject”.
Claim 34 recites alternative administration order while punctuation mark is missing between (a) and (b).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Written Description Rejection
Claims 1, 2, 9-13, 15, 21, 22, 24, 25, 33 and 34 are rejected under 35 U.S.C. 112 (a), first paragraph, as failing to comply with the written description requirement. Claims 1, 2, 9-13, 15, 21, 22, 24, 25, 33 and 34 contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor, at the time the application was filed, had possession of the full scope of method genus of treating all KRAS mutant cancer comprising administering to the subject an effective amount of any KRAS inhibitor and poziotinib. This is a written description rejection, rather than an enablement rejection under 35 U.S.C. 112, first paragraph. Applicant is directed to the MPEP 2163 and Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, 1st "Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.
MPEP 2163.02 states “ Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, the inventor was in possession of the invention, and that the invention, in that context, is whatever is now claimed.”
Instant claims are drawn to method of treating KRAS mutant cancer with combination of a KRAS inhibitor and poziotinib. Although claims 15 and 33 recites narrow scope of KRAS G12C mutant cancer, e.g. non-small cell lung cancer, instant claims are still drawn to vast variety of KRAS inhibitors that have different chemical structures, different chemical and physical properties and different pharmaceutical activity against different KRAS mutant cancer.
The Applicant is required to provide adequate written description and evidence of possession of instant claimed genus, i. e, method of treating variety of KRAS mutant cancer with combination genus of KRAS inhibitor genus and poziotinib. MPEP 2163 II states; “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above)”. While applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. “A representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus”.
Instant specification discloses working examples comprising sotorasib or adagrasib as exemplary KRAS inhibitor in combination with poziotinib in KRAS G12C mutant non-small cell lung cancer cell lines (See Example 7-9). Instant specification does not provide working example comprising other structurally distinct KRAS inhibitors in combination with poziotinib for treating any KRAS mutant cancer. Instant specification does not provide working example for treating KRAS mutant colorectal cancers or other KRAS mutant cancers. Instant specification does not provide working example wherein the subject was previously treated with other KRAS inhibitors. Instant specification does not provide working example wherein the subject is treated with additional cancer therapy. As such, the instant specification does not provide a sufficient written description to establish the full scope of instant claimed method of treating various KRAS mutant cancer with instantly claimed combination genus comprising KRAS inhibitor genus and poziotinib. The specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed.
Applicant is reminded that MPEP 2161 II makes clear that “ The written description requirement is separate and distinct from the enablement requirement”.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 6, 22, 34 and 38 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 2 and 34 recites “wherein the KRAS inhibitor and poziotinib are administered (a) substantially simultaneously, (b) the KRAS inhibitor and poziotinib are administered sequentially, (c) the KRAS inhibitor is administered prior to administering poziotinib, or (d) the KRAS inhibitor is administered subsequent to administering poziotinib”. Instant spec (See [0034]) discloses the KRAS inhibitor and poziotinib may be administered sequentially (at different times) or concurrently (at or at approximately the same time; also “substantially simultaneously”). These alternative administration order are overlapping and confusing wherein (b) KRAS inhibitor and poziotinib administered sequentially comprises (c) and (d).
Claim 6 recites “wherein the KRAS inhibitor is a KRASG12C inhibitor, sotorasib (AMG 510), or adagrasib (MRTX849)”. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 6 recites the broad recitation of “KRASG12C inhibitor” and the claim also recites “sotorasib (AMG 510), or adagrasib (MRTX849)” which is the narrower statement of the limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 22 recites the KRAS inhibitor and poziotinib are administered once per day for multiple days or twice per day for multiple days. It’s not clear what’s the time period of “multiple days”, two days or 20 days, or 100 days?
Claim 38 is drawn to “a method of claim 33, any of claims 33-37”. First, claims 35-37 are cancelled, it’s not clear what subject matter in claims 35-37 is claim 38 referred back to. Second, the scope of independent claim 33 is broader than dependent claim 34. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 38 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 38 is drawn to “a method of claim 33, any of claims 33-37”. Claims 35-37 are cancelled, it’s not clear what subject matter in claims 35-37 is claim 38 referring back to. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 6, 9-13, 15, 21, 22, 24, 25, 33 and 34 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Engstrom et al. ( WO2020/055756 A1, Applicant’s IDS dated 07/01/2025).
Engstrom discloses combination therapy comprising a KRAS G12C inhibitor with a pan ErbB family inhibitor (e.g. poziotinib), pharmaceutical compositions comprising therapeutically effective amount of the inhibitors and a pharmaceutically acceptable excipient, and method for use in the treatment of KRAS G12C-associated cancer (e.g. lung cancer) (See abstract, [0001], [0008], [0036] - [0038], [0180], Examples A, B; Table 3; claims 1-90). Engstrom discloses KRAS G12C inhibitor of formula (I) and explicitly teaches the pan ErbB family inhibitor is poziotinib (See [0038], [0095],[0164], [0166], Example A, Table 3, claim 63, etc. ). Engstrom teaches embodiments wherein the combination of pan ErbB family inhibitor and KRAS G12C inhibitor results in an increased duration of overall survival, an increased duration of progression free survival, an increase in tumor growth regression, an increase in tumor growth inhibition or an increased duration of stable disease in the subjects relative to treatment with only the Kras G12C inhibitor (See [0083], [0074], Experiment A, B, claim 76).
Regarding claim 2 and 34, Engstrom teaches pan ErbB family inhibitor and/or a Kras G12C inhibitor may be used simultaneously or sequentially, e. g. the pan ErbB family inhibitor is administered prior to or after administration of the KRas G12C inhibitor (See [0151]-[0152]).
Regarding claim 9, Engstrom teaches embodiments for treating cancer in a subject comprising determining that cancer associated with a KRas G12C mutation (See [0179]).
Regarding claims 10-13, and 24-25, Engstrom teaches embodiments wherein the patient was previously treated with one or more of cancer therapy, e.g. chemotherapy with kinase inhibitor, etc. wherein previous treatment was unsuccessful (See [0190]). Engstrom teaches embodiments wherein pan ErbB family inhibitor (e.g. poziotinib), or a pharmaceutically acceptable salt or a pharmaceutical composition thereof is administered in combination with the Kras G12C inhibitor once disease progression has been observed for KRas G12C monotherapy, in which the combination therapy results in enhanced clinical benefit(See [0180]).
Regarding claims 15 and 33, Engstrom teaches method of treating variety of KRas G12C-associated cancer, e.g. non-small cell lung cancer, etc. (See [0178]-[0179], [0188], claims 86-87). Engstrom teaches embodiments wherein the pan ErbB family inhibitor synergistically increases the sensitivity of the cancer cells (e.g. lung cancer, etc.) to the KRas G12C inhibitor(See Example A, Table 3, claims 78-80).
Regarding claims 21 and 22, Engstrom teaches oral administration of KRas G12C inhibitor and pan ErbB inhibitor once a day during a period of time (See [0181]-[0182]).
Engstrom collectively teaches a method of treating KRAS mutant cancer (e.g. non-small cell lung cancer) in a subject in need thereof with combination therapy comprising a KRAS G12C inhibitor and ErbB family inhibitor (e.g. poziotinib). Thus, Engstrom anticipates instant claimed invention.
Claims 1, 2, 6, 9-13, 15, 21, 22, 24, 25, 33-34 and 38 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Kulkarni et al. (WO 2022031952 A2, Applicant’s IDS dated 06/21/2024).
Kulkarni discloses combination therapy comprising a KRAS G12C inhibitor (e.g. sotorasib/AMG 510) with ITGB4/PXN pathway inhibitor (e.g. carfilzomib, poziotinib), pharmaceutical compositions comprising therapeutically effective amounts of the inhibitors and a pharmaceutically acceptable excipient, and method for use in the treatment of cancers having KRAS mutations (e.g. lung cancer) (See abstract, [0007], [0009], [0012], [0084], [0203]-[0206], Examples 1-5, claims 1-72). Kulkarni teaches embodiments comprising poziotinib as ITGB4/PXN pathway inhibitor(See [0049], [0080], claim 36).
Regarding claim 2 and 34, Kulkarni teaches combination embodiments wherein the inhibitors /agents may be used simultaneously, concomitantly, or by sequential administration of two or more agents or compositions (See [0110]).
Regarding claims 6 and 38, Kulkarni teaches embodiments comprising variety of Kras inhibitor, e.g. sotorasib/AMG 510, adagrasib, etc. (See [0082], [0146]-[0153], Example 1-5) and ITGB4/PXN pathway inhibitor (e.g. carfilzomib, poziotinib) (See [0049], [0080], [0084]-[0085], [0143] , [0159], [0207], claim 36 and 59) and combination thereof. Kulkarni teaches combination of poziotinib and sotorasib at an effective amount wherein the cancer has a KRAS Gl2 mutation (See page 31, [0084])(which reads on instant elected species).
Regarding claim 9, Kulkarni teaches embodiments comprising identifying a homozygous KRAS mutation in a biological sample obtained from the subject; measuring a KRAS mutation in a biological sample obtained from the subject and cancers associated with a Kras G12C mutation (See [0012], [0127], [0135]-[0136], [0194], [0203]-[0204], [0251], claim 23).
Regarding claims 10-13, and 24-25, Kulkarni teaches embodiments wherein the patient was previously treated with one or more of cancer therapy, e.g. KRAS inhibitor, etc. (See [0054]). Kulkarni also teaches KRAS inhibitor resistant subject wherein patients who are initially responsive to
treatment with a KRAS inhibitor, but then became resistant to the KRAS inhibitor over time (See [0055], claim 4).
Regarding claims 15 and 33, Kulkarni teaches variety of KRas G12C-associated cancer, e.g. non-small cell lung cancer, pancreatic cancer. etc. (See [0083], [0085], [0223], [0227]-[0228], [0248], claims 56, 57).
Regarding claims 21 and 22, Kulkarni teaches oral formulation (See [0098], [0101]) and combination therapy can be administered to the subjects on a daily, twice daily, bi-weekly or any applicable basis that is therapeutically effective (See [0110], [0305]).
Regarding claims 24-25, Kulkarni teaches additional cancer therapy, e.g. anticancer agent, chemotherapy agent, etc. can be used (See [0104]-[0107]).
Kulkarni collectively teaches a method of treating KRAS mutant cancer (e.g. non-small cell lung cancer) in a subject in need thereof with combination therapy comprising a KRAS G12C inhibitor (e.g. sotorasib, adagrasib, etc. ) and ITGB4/PXN pathway inhibitor (e.g. poziotinib). Thus, Kulkarni anticipates instant claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, 6, 9-13, 15, 21, 22, 24, 25, 33, 34, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Engstrom et al. ( WO2020/055756 A1, Applicant’s IDS dated 07/01/2025) in view of LUMAKRAS™ (sotorasib) label 2021.
The collective teachings of Engstrom are elaborated in preceding 102 rejection and applied as before. Engstrom collectively teaches a method of treating KRAS mutant cancer (e.g. non-small cell lung cancer) in a subject in need thereof with combination therapy comprising a KRAS G12C inhibitor and ErbB family inhibitor (e.g. poziotinib).
Engstrom is silent about sotorasib/AMG 510 as the KRAS inhibitor as recited in instant claims 6 and 38.
LUMAKRAS™ (sotorasib) is an inhibitor of RAS GTPase family, approved by FDA in 2021 for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy(See INDICATIONS AND USAGE).
Combination therapy is a well-known practice in cancer treatment as demonstrated by Engstrom. It would have been prima facie obvious to one of the ordinary skilled in the art before the effective filing date of instantly claimed invention to explore Engstrom combination therapy comprising a KRAS inhibitor and ErbB family inhibitor (e.g. poziotinib) by incorporating sotorasib/AMG 510 as the KRAS inhibitor, together with general knowledge of cancer treatment and arrived instantly claimed invention with reasonable expectation of success. A skilled artisan would be motivated to explore sotorasib/AMG 510 as the KRAS inhibitor since sotorasib/AMG 510 is approved by FDA for treating KRAS G12C-mutated non-small cell lung cancer (NSCLC), and reasonably expected that combination of sotorasib/AMG 510 with ErbB family inhibitor (e.g. poziotinib) would provide an alternative combination therapy for KRAS G12C-mutated cancer (e.g. non-small cell lung cancer).
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and exploration/optimization based on the general knowledge of cancer treatment. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 2, 6, 9-13, 15, 21, 22, 24, 25, 33, 34, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Engstrom et al. (WO2020/055756 A1, Applicant’s IDS dated 07/01/2025), in view of Lipford et al. (US 2020/0222407 A1, Applicant’s IDS dated 06/21/2024).
The collective teachings of Engstrom are elaborated in preceding 102 rejection and applied as before. Engstrom collectively teaches a method of treating KRAS mutant cancer (e.g. non-small cell lung cancer) in a subject in need thereof with combination therapy comprising a KRAS G12C inhibitor and ErbB family inhibitor (e.g. poziotinib).
Engstrom is silent about sotorasib (AMG 510) recited in instant claims 6 and 38.
Lipford teaches combination therapy comprising a KRAS G12c inhibitor (e.g. sotorasib/AMG510) and one or more additional pharmaceutically active agents, e.g. chemotherapeutic agent, HER kinases inhibitor, EGFR inhibitor, etc. for treatment of KRAS mutant cancer (See abstract, [0009], [0014] -[0236], Examples, Table A, claims 1-86). Lipford teaches enhanced efficacy in combination therapy wherein combinations of AMG 510 with other pathways inhibitors might enhance tumor cell killing and overcome resistance (See [0595]-[0596]), Lipford teaches embodiments comprising variety of EGFR inhibitors/antibodies, e.g. afatinib, erlotinib, lapatib, cetuximab, etc. (See [0027]-0032], [0147], [0574],Table A ) and AMG 510 combined with afatinib is synergistic in inhibiting NCI-H358 cell line (human non-small cell lung cancer )(See [0265]).
Regarding claim 2 and 34, Lipford teaches Kras G12C inhibitor and one additional pharmaceutically active agent are administered simultaneously or separately (See [0230]-[0231], [0463], claims 85-86).
Regarding claim 9, Lipford teaches embodiments for treating cancer in a subject comprising determining if the subject has a KRAS, HRAS or NRAS G12C mutation (See [0389]-[0395]).
Regarding claims 10-13, Lipford teaches embodiments wherein the patient was previously treated with one or more of cancer therapy, e.g. chemotherapy etc. (See [0594]). Lipford teaches KRAS mutations have been found to confer resistance to epidermal growth factor receptor (EGFR) targeted therapies, accordingly, the mutational status of KRAS can provide important information for TKI therapy (See [0004]).
Regarding claims 15 and 33, Lipford teaches method of treating variety of KRas G12C-associated cancer, e.g. non-small cell lung cancer, etc. (See [0018], claim 7-8). Lipford teaches KRAS mutations are observed in about 25% of patients with NSCLC(See [0004]).
Regarding claims 21 and 22, Lipford teaches oral administration of KRas G12C inhibitor (AMG 510) and other anticancer agent, e.g. MEK inhibitor, once a day for a period of time (See [0530], [0615], [0617]-[0618]).
Regarding claims 24-25, Lipford teaches embodiments wherein the patient was treated with at least one additional pharmaceutically active agent, e.g. anti-PD-1 inhibitor, a MEK inhibitor, an EGFR inhibitor, a TOR inhibitor, a SHP2 inhibitor, a PI3K inhibitor or an AKT inhibitor (See [0112], [0136], [0161], claims 12,39).
Combination therapy is a well-known practice in cancer treatment as demonstrated by Engstrom and Lipford. It would have been prima facie obvious to one of the ordinary skilled in the art before the effective filing date of instantly claimed invention to explore Engstrom combination therapy comprising a KRAS inhibitor and ErbB family inhibitor (e.g. poziotinib) by incorporating sotorasib/AMG 510 taught by Lipford as the KRAS G12C inhibitor, together with general knowledge of cancer treatment and arrived instantly claimed invention with reasonable expectation of success. Lipford teaches variety of combination therapy comprising sotorasib/AMG 510 wherein the combination comprising sotorasib/AMG 510 and afatinib synergistically inhibits KRAS mutant cell lines. A skilled artisan would be motivated to explore sotorasib/AMG 510 as the KRAS G12C inhibitor and reasonably expect that combination of sotorasib/AMG 510 with ErbB family inhibitor (e.g. poziotinib) would provide an alternative combination therapy for KRAS G12C-mutated cancer (e.g. non-small cell lung cancer) with complementary pathways that enhance efficacy in treatment and overcome resistance.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and exploration/optimization based on the general knowledge of cancer treatment. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 2, 6, 9-13, 15, 21, 22, 24, 25, 33, 34, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Lipford et al. (US 2020/0222407 A1, Applicant’s IDS dated 06/21/2024), in view of Robichaux et al. (WO2018094225 A1, hereafter Robichaux’ 225, Applicant’s IDS dated 06/21/2024).
The collective teachings of Lipford are elaborated in preceding 103 rejection and applied as before. Lipford collectively teaches a method of treating KRAS mutant cancer (e.g. non-small cell lung cancer) in a subject in need thereof with combination therapy comprising a KRAS G12 inhibitor (sotorasib /AMG 510) and a variety of HER kinases inhibitor, EGFR inhibitor (e.g. afatinib), etc..
Lipford is silent about poziotinib.
Robichaux’ 225 teaches methods of treating cancer in a patient determined to have an EGFR and/or HER2 exon 20 mutation by administering a third-generation tyrosine kinase inhibitor, e.g. poziotinib or afatinib (See abstract, [0007]-[0017], [0036], claims 1-65). Robichaux’ 225 teaches combination therapy comprising poziotinib or afatinib in combination with at least one additional therapy, e.g. chemotherapy to improve the therapeutic efficacy (See [0081]- [00104], claims 35, 64-65).
Regarding claim 2 and 34, Robichaux’ 225 teaches poziotinib may be administered before, during, after, or in various combinations relative to the additional cancer therapy for a period of time (See [0083]).
Regarding claims 15 and 33, Robichaux’ 225 teaches method of treating variety of cancer, e.g. non-small cell lung cancer, etc. (See [0011], [0017], [0076], claims 18 and 52).
Regarding claims 21 and 22, Robichaux’ 225 teaches oral administration of poziotinib and/or anti-cancer therapy two times daily, every other day, or weekly (See [0010], claims 14 and 16).
Regarding claims 24-25, Robichaux’ 225 teaches embodiments comprising poziotinib in combination with at least one additional therapy, e.g. chemotherapy, radiotherapy, gene therapy, surgery, hormonal therapy, anti-angiogenic therapy or immunotherapy (See [0081], claims 12-13).
"It is prima facie obvious to combine two compositions, each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." Jn re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Combination therapy is a well-known practice in cancer treatment as demonstrated by Lipford and Robichaux’ 225. It would have been prima facie obvious to one of the ordinary skilled in the art before the effective filing date of instantly claimed invention to explore more combination therapy comprising a KRAS inhibitor and tyrosine kinase inhibitors (e.g. poziotinib) based on the combined beneficial teachings of Lipford and Robichaux’ 225, together with general knowledge of cancer treatment and arrived instantly claimed invention with reasonable expectation of success. Lipford teaches variety of combination therapy comprising sotorasib/AMG 510 for treating KRAS mutant cancer (e.g. non-small cell lung cancer) , wherein the combination comprising sotorasib/AMG 510 and afatinib synergistically inhibits KRAS mutant NSCLC cell lines. Robichaux’ 225 teaches poziotinib and combination therapy for treating non-small cell lung cancer. In search for alternative combination therapy for treating KRAS mutant cancer, a skilled artisan would be motivated to explore combination of KRAS G12C inhibitor and poziotinib, and reasonably expect that combination of sotorasib/AMG 510 with poziotinib would provide an alternative combination therapy for KRAS G12C-mutated cancer (e.g. non-small cell lung cancer) with complementary pathways that enhance efficacy in treatment and overcome resistance.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and exploration/optimization based on the general knowledge of cancer treatment. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 6, 9-13, 15, 21, 22, 24, 25, 33- 34 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-10 and 14 of U.S. Patent No. 11446302, in view of Kulkarni et al. (WO 2022031952 A2, Applicant’s IDS dated 06/21/2024).
Reference claims are directed to a method of treating cancer in a subject comprising administering an effective amount of poziotinib to the subject, wherein the subject has a tumor that has been determined to have one or more EGFR exon 20 insertion mutations.
Reference claims 7-10 recite administering an additional anti-cancer therapy.
Reference claim 14 recites variety of cancer, e.g. non-small cell lung cancer.
Reference claims are silent about the additional anti-cancer therapy is KRAS inhibitor.
The collective teachings of Kulkarni are elaborated in preceding 102 rejection and applied as before. Kulkarni collectively teaches a method of treating KRAS mutant cancer (e.g. non-small cell lung cancer) in a subject in need thereof with combination therapy comprising a KRAS G12C inhibitor (e.g. sotorasib, adagrasib, etc. ) and ITGB4/PXN pathway inhibitor (e.g. poziotinib).
Combination therapy is a well-known practice in cancer treatment as demonstrated by Kulkarni. It would have been prima facie obvious to one of the ordinary skilled in the art to explore combination therapy comprising poziotinib taught by reference claims and KRAS inhibitor based on the combined beneficial teachings of Kulkarni, together with general knowledge of cancer treatment and arrived at instant claimed invention with reasonable expectation of success.
The instant application shares at least one common inventor/applicant with the reference patent. Further, instant application is not related to the reference patent and thus no 35 USC 121 shield exists.
Claims 1, 2, 6, 9-13, 15, 21, 22, 24, 25, 33- 34 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, and 11-14 of U.S. Patent No. 12629375, in view of Kulkarni et al. (WO 2022031952 A2, Applicant’s IDS dated 06/21/2024).
Reference claims are directed to a method of treating cancer in a subject comprising administering an effective amount of poziotinib to the subject, wherein the subject has a tumor that has been determined to have one or more EGFR exon 21 insertion mutations.
Reference claims 4-5 recite the subject is resistant to the previously administered tyrosine kinase inhibitor.
Reference claims 11-12 recite administering an additional anti-cancer therapy.
Reference claim 13-14 recites variety of cancer, e.g. non-small cell lung cancer.
Reference claims are silent about the additional anti-cancer therapy is KRAS inhibitor.
The collective teachings of Kulkarni are elaborated in preceding 102 rejection and applied as before. Kulkarni collectively teaches combination therapy comprising a KRAS G12C inhibitor (e.g. sotorasib, adagrasib, etc. ) and ITGB4/PXN pathway inhibitor (e.g. poziotinib) for treating KRAS mutant cancer (e.g. non-small cell lung cancer) in a subject in need thereof.
Combination therapy is a well-known practice in cancer treatment as demonstrated by Kulkarni. It would have been prima facie obvious to one of the ordinary skilled in the art to explore combination therapy comprising poziotinib taught by reference claims and KRAS inhibitor based on the combined beneficial teachings of Kulkarni, together with general knowledge of cancer treatment and arrived at instant claimed invention with reasonable expectation of success.
The instant application shares at least one common inventor/applicant with the reference patent. Further, instant application is not related to the reference patent and thus no 35 USC 121 shield exists.
Claims 1, 2, 6, 9-13, 15, 21, 22, 24, 25, 33- 34 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7- 18 of U.S. Patent No. 12714708, in view of Kulkarni et al. (WO 2022031952 A2, Applicant’s IDS dated 06/21/2024).
Reference claims are directed to a method of treating cancer in a subject comprising administering an effective amount of poziotinib to the subject, wherein the subject has a tumor that has been determined to have one or more HER2 exon 19 mutations.
Reference claims 7-8 recite administering an additional anti-cancer therapy.
Reference claim 17 recites non-small cell lung cancer.
Reference claims are silent about the additional anti-cancer therapy is KRAS inhibitor.
The collective teachings of Kulkarni are elaborated in preceding 102 rejection and applied as before. Kulkarni collectively teaches combination therapy comprising a KRAS G12C inhibitor (e.g. sotorasib, adagrasib, etc. ) and ITGB4/PXN pathway inhibitor (e.g. poziotinib) for treating KRAS mutant cancer (e.g. non-small cell lung cancer) in a subject in need thereof.
Combination therapy is a well-known practice in cancer treatment as demonstrated by Kulkarni. It would have been prima facie obvious to one of the ordinary skilled in the art to explore combination therapy comprising poziotinib taught by reference claims and KRAS inhibitor based on the combined beneficial teachings of Kulkarni, together with general knowledge of cancer treatment and arrived at instant claimed invention with reasonable expectation of success.
The instant application shares at least one common inventor/applicant with the reference patent. Further, instant application is not related to the reference patent and thus no 35 USC 121 shield exists.
Conclusion
No claims are allowed.
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/LIYUAN MOU/ Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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