DETAILED ACTION
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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The application is the national stage entry of PCT/US2021/062832, which claims benefit to U.S. Provisional Application No. 63/124.231, filed December 11, 2020.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on June 9, 2023 and January 5, 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs are being considered by the examiner.
The listing of references in the specification (see pg 41-47) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112(b)
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 4 and 9 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.
Claim 4 recites the phrase wherein the melanoma is a “PD-1 refractory melanoma”. This limitation is unclear because the melanoma is not refractory to PD-1 but is refractory to the anti-PD-1 antibody therapy. Since PD-1 is an immune checkpoint protein and not the inhibitor, the claim is indefinite for not properly defining the melanoma claimed. A melanoma that is refractory to anti-PD-1 antibody treatment is “anti-PD-1 refractory melanoma”.
The term “about” in claim 9 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree (see pg 10 of specification), and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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 1-3 and 10-17 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO 2018226690, published December 13, 2018 (“Gajewski”; IDS from 6/9/2023).
Gajewski teaches method for treating cancer in a subject by c0-administering an anti-PD-1 antibody and fecal material from a donor that is a responder to anti-PD-1 therapy (Figure 3), which reads on instant claim 1. Gajewski identified anti-PD-1 responders and non-responders by assessing relative abundance of differentially abundant taxa of bacteria (see Figure 1A-B).
The cancer is melanoma or malignant melanoma (pg 7, ln 18-21), which reads on instant claims 2-3.
Gajewski teaches that Lachnospiraceae bacterium and Bifidobacterium longum are elevated in responders (see Table 5), which reads on the bacteria limitations of claims 10-12.
The bacterial formulation of Gajewski is administered in some embodiments as two or more doses or one dose (pg 7, 10), which reads on instant claim 13.
Gajewski teaches that the bacterial formulation and cancer therapy can be co-administered (pg 18, 30) and that the bacterial formulation may be delivered as two or more doses (pg 7, 10), which reads on the additional administrations of the anti-PD-1 antibody to the subject in instant claim 14.
The anti-PD-1 antibody of Gajewski may be nivolumab or pembrolizumab (pg 10), which reads on instant claim 15.
While Gajewski is silent on the intended results of the effect of the anti-PD-1 antibody and fecal sample on the level of bacteria in phylum Firmicutes and/or phylum Actinobacteria in the subject’s gut, as required by claim 16, and decrease a level of bacteria of phylum Bacteroides anti-FcRn antibody in the subject’s gut, as required by claim 17, it is clear that the same patient population treated with the same antibody in combination with the same fecal sample would have the same characteristics and effects as the instantly claimed combination since there is no evidence to the contrary. Note that rejections for anticipation or obviousness are appropriate when the prior art discloses a method (or product) that appears to be identical except that the art is silent as to an inherent property; see MPEP § 2112(III). In such situations, the burden is on applicant to provide evidence that the prior art product (or method) is not the same.
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.
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 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018226690 (“Gajewski”).
Gajewski teaches method for treating cancer in a subject by administering anti-PD-1 antibody and fecal material from a donor that is a responder to anti-PD-1 therapy (Figure 3), wherein the cancer is melanoma or malignant melanoma (pg 7, ln 18-21). Gajewski does not make reference to PD-1 refractory melanoma nor does it make reference to subjects that are less responsive than the donor to anti-PD-1 antibody or non-responsive to anti-PD-1 antibody therapy, as required by instant claims 4-6. However, given that Gajewski teaches that combination therapy with the anti-PD-1 antibody and fecal material from a donor that is a responder to anti-PD-1 therapy is effective reduce tumor volume in a mouse model of melanoma (Figure 3F), it would have been obvious to one of ordinary skill in the art to apply the treatment method of Gejewski to a patient who is non-responsive to anti-PD-1 monotherapy. One would do so and have a reasonable expectation of successfully treating this patient, as the combination therapy demonstrates improved anti-tumor efficacy over anti-PD-1 monotherapy (see Figure 3A and Figure 3F).
Claim 7 is directed to a donor that is responsive to a combination of anti-PD-1 antibody and anti-CTLA-4 antibody; claim 8 limits the donor to one diagnosed with melanoma. The donors of Gajewski have been diagnosed with melanoma (Table 1), as in instant claim 8. Gajewski teaches that fecal samples were collected from patients who were subjected to an anti-PD-1 therapy or an anti-CTLA-4 therapy, and there were responders in both groups (pg 48). Given that these donors were responsive to either anti-PD-1 or anti-CTLA-4 monotherapy, it would have been obvious to one or ordinary skill in the art that these donors would also be responsive to a combination therapy and that this fecal sample would be at least effective as those receiving only one checkpoint inhibitor. Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalence for the same purpose: "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 they having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted).
Gajewski teaches clinical response rate (i.e. responsiveness) to anti-PD-1 in donors was determined using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (pg 84, ln 3-8), which assesses levels of tumor shrinkage and disease progression (as evidenced by Eisenhauer et al, abstract, see IDS from 1/5/2024, NPL 30). Instant claim 9 is limited to donors having progression-free survival (PFS) of at least about 36 months. Given that Gajewski teaches donors who are responsive to PD-1 therapy, as determined by RECIST criteria, it would have been obvious to the ordinary artisan to select donors with PFS of 36 months, especially in the absence of unexpected results. It is the Office’s position that this species within the “responder” genus of Gajewski can be at once envisaged from the prior art because the species within this genus (e.g., donor with PFS of at least 36 months) are sufficiently limited and well delineated; see MPEP 2131.02(III) and In re Petering (wherein the courts determined that a reference describing a generic formula encompassing about 20 compounds was found to anticipate each of the 20 species without specifically naming them).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675