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 .
Election/Restrictions
Applicant's election with traverse of Species (1): claims 1-6 and 14-17 in the reply filed on June 30, 2025 is acknowledged. The traversal is on the ground(s) that the Examiner has not met the burden of establishing a serious search burden. This is not found persuasive because Applicant is reminded that the instant restriction requirement is made under lack of unity and establishing a serious search burden is not required.
The requirement is still deemed proper and is therefore made FINAL.
Claims 7-13 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on June 30, 2025.
Applicant's election with traverse of the species: BRAF inhibitor: vemurafenib, MEK inhibitor: trametinib dimethyl; and Cancer: melanoma in the reply filed on June 30, 2025 is acknowledged. The traversal is on the ground(s) that a reasonable number of species of inhibitors or agonists should be examined. This is not found persuasive because While the dependent claims are limited to a few species of inhibitors and agonists, the independent claims are generic and the broadest reasonable interpretation reads the entire genus of inhibitors and agonists. Therefore, the claims are not limited to a few species as argued by applicant. Additionally, the claims are directed to structurally and chemically distinct inhibitors and agonists which do not share a common core.
The requirement is still deemed proper and is therefore made FINAL.
Application Status
Claims 1-20 are pending.
Claims 7-13 and 18-20 are withdrawn.
Claims 1-6 and 14-17 are examined on the merits herein.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The use of the term Mekinist® (para 12 and 54), Abraxane® (para 55), Abitrexate™ (para 55), Sylatron™ (para 55), Zelboraf® (para 55) and a number of other terms in paragraph 55, Matrigel® (para 75) which are a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 102
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 1-6 and 14-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fritsch (US 2018/0153975 A1; IDS entered August 12, 2021).
Regarding claims 1-2, 5-6, and 17, Fritsch teaches method of treating or preventing a tumor in a population of subjects in need thereof, comprising administering to a subject an agent comprising an extracellular ligand-binding domain recognizing a tumor-specific neoepitope…wherein agent may be CAR or T cell receptor (para 0050). Fritsch further teaches that the treatment comprises an inhibitor of BRAF, such as Vemurafenib, used as an additional agent and that BRAF inhibition has been shown to be associated with an increase in melanoma antigen expression and T-cell infiltrate and a decrease in immunosuppressive cytokines in tumors of treated patients (para 0666), this would increase the sensitivity of cancer to ACT as required by claim 2. Fritsch further teaches wherein treatment efficacy is determined by monitoring a biomarker including IGF-II (IGF2R). As evidenced by the instant claims, treatment with a BRAF inhibitor will increase IGF2R.
Regarding claims 3 and 16, the solid tumor may be melanoma (para 0012).
Regarding claims 4 and 14-15, Fritsch teaches tumor specific mutations that are drug resistance mutations and that the drug resistant mutation can be induced by treatment with vemurafenib (para 0028), therefore the drug resistant mutation would induce BRAF inhibitor resistance.
Regarding claim 14, Fritsch teaches herein the population suffering from cancer was treated with, is being treated with, or is selected to be treated with RAF/MEK inhibitor (para 0086).
Claims 1-3, 5-6, and 16-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Svane (NCT02354690 record history 10/10/2018; PTO-892).
Regarding claims 1-3, 5-6, and 16-17, Svane teaches treatment of metastatic melanoma with tumor infiltrating lymphocytes with a BRAF inhibitor (vemurafenib) as vemurafenib has immunomodulatory effects thought to synergize with TIL therapy (brief summary). As evidenced by the instant claims, treatment with a BRAF inhibitor will increase IGF2R.
The immunomodulatory effects of vemurafenib that synergize with TIL therapy meet the limitation of increasing the sensitivity of a cancer to adoptive cell therapy as recited in claim 2.
Claim Rejections - 35 USC § 103
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 nonobviousness.
Claims 4, 14, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Svane (NCT02354690 record history 10/10/2018; PTO-892) as applied to claim 1-3, 5-6, and 16-17 above, and further in view of Kakadia (Onco Targets Ther, 2018 Oct 17, 11:7095-7107; IDS entered August 12, 2021).
The teachings of Svane are detailed above.
Svane does not teach wherein the cancer is BRAF inhibitor resistant cancer or wherein the method further comprises administering to the subject a MEK inhibitor.
Regarding claims 4 and 5, Kakadia teaches that treatment with a BRAF inhibitor results in a high response rate but that the response is short lived (introduction) and that combining adoptive T cell transfer with BRAF inhibitor treatment improves antitumor activity , in vivo cytotoxic activity and intratumoral cytokine secretion as one way to overcome BRAF inhibitor resistance (page 7099, col 1, para 1).
Regarding claim 14, Kakadia teaches that treatment with BRAF inhibitor and specifically vemurafenib leads to genetic alteration in over 50% of patients that result in reactivation of the MAPK and to a lesser extent the PI3K/Akt pathways which are acquired resistance mechanisms (page 7096, col 1, paras 2-3; summarized in Table 1). Kakadia further teaches that adding MEK inhibitor to BRAF inhibitor treatment can overcome resistance to BRAF inhibitors and enhance immunosurveillance (page 7098, last para- page 7099, first para). Kakadia further teaches combined BRAF-MEK inhibitor therapy is the standard of care for BRAF V600 mutant advanced melanoma, including vemurafenib combined with cobimetinib (page 7104, col 1, para 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to treat BRAF resistant cancer and to add a MEK inhibitor as taught by Kakadia to the method of treatment of melanoma with ACT and a BRAF inhibitor as taught by Svane. The ordinary artisan would have been motivated to do so as Kakadia teaches that treatment with a BRAF inhibitor has short term benefits and results in resistance in more than half of patients that are treated. Kakadia further teaches that adoptive cell transfer combination with BRAF inhibition treatment may overcome BRAF inhibitor resistance as it augments the antitumor activity. Kakadia further teaches that combination treatment with a BRAF inhibitor with a MEK inhibitor is an FDA approved standard of care for BRAF V600 advanced melanoma and a MEK inhibitor can overcome BRAF inhibitor resistance and enhance immunosurveillance. Therefore the ordinary artisan has a reasonable expectation of success to overcome BRAF resistance in cancer therapy with combination therapy comprising ACT and a BRAF inhibitor and further augmenting results with the addition of a MEK inhibitor.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMBER K FAUST whose telephone number is (703)756-1661. The examiner can normally be reached Monday - Thursday 9:00am-6:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMBER K FAUST/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643