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 .
Status of the Claims
Claims 1-3, 5-17, and new claim 18 are under consideration in this office action.
Withdrawn Rejections
Any objection or rejection of record pertaining to cancelled claim 4 is rendered moot by applicant’s cancellation of said claim.
The rejection of claim 9 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of applicant’s amendment.
The rejection of claims 1-3 and 10-17 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO-2018226690 (“Gajewski”) is withdrawn in view of the new limitation of claim 1 directed to a subject who is refractory to anti-PD-1 antibody therapy.
New Rejections Necessitated by Amendment
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.
Claim 15 is 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 15 recites that “the anti-PD-1 antibody is pembrolizumab or nivolumab”. This claim, which is dependent on amended claim 1, is indefinite because it is unclear which antibody of claim 1 this limitation of claim 15 is directed. There are two anti-PD-1 antibodies in claim 1; the antibody that is administered to the subject in a method of treating and the antibody that was administered to the responsive donor. In the interest of compact prosecution, the antibody will be interpreted to be the one administered to the subject in need.
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, 5-6, 8, 14-17 and new claim 18are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Baruch et al, published online December 10, 2020 (instant PTO-892).
Baruch et al teaches a method of treating metastatic melanoma patients who are refractory to anti-PD-1 therapy with fecal microbiota transplantation (FMT) and anti-PD-1 therapy (abstract), which reads on the method of claim 1 and the refractory anti-PD-1 melanoma and anti-PD-1 metastatic melanoma of claims 2-3. FMT donors were two metastatic melanoma patients who achieved durable complete response following treatment with anti-PD-1 monotherapy for metastatic melanoma (abstract, pg 1, column 2, para 1), which reads on the limitation of claim 1 wherein the donor is responsive to an anti-PD-1 antibody therapy, the limitation of claim 5 wherein the subject is less responsive to anti-PD-1 antibody than the donor, and the limitation of instant claim 7 wherein the donor has been diagnosed with melanoma.
As shown in Table 1 of Baruch et al, recipients 1, 3-4, and 9 of the combination FMT/anti-PD-1 therapy were non-responsive to previous anti-PD-1 antibody monotherapy (pg 4), which reads on instant claim 6. The FMT was administered every 14 days for 90 days (pg 1, column 3, para 0), which reads on the limitation of claim 14 directed to a method comprising one or more additional administrations of the anti-PD-1 antibody to the subject. Baruch et al teaches that the patients received nivolumab (pg 1, column 3, para 0), which reads on instant claim 15.
Regarding the human limitation of new claim 18, Baruch et al teaches administration of the combination therapy to patients (abstract).
While Baruch et al 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 the level of bacteria of phylum Bacteroides 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 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.
Claims 1-3, 5-17 and new claim 18 are rejected under 35 U.S.C. 103 as being unpatentable over Baruch et al, published online December 10, 2020 in view of WO 2018226690, published December 13, 2018 (“Gajewski”; IDS from 6/9/2023).
The teachings of Baruch et al are discussed above. Baruch et al does not explicitly teach
wherein the donor is responsive to a combination of anti-PD-1 antibody and anti-CTLA-4 antibody of instant claim 7. Baruch et al does not teach wherein the donor has a progression-free survival of at least 36 months, as required by instant claim 9. Baruch does not teach the bacterial composition of the fecal material from a donor that is a responder to anti-PD-1 therapy, as required by instant claims 10-12. Baruch does not teach the limitation wherein the fecal sample is only administered once, as required by claim 13.
Gajewski teaches method for treating cancer in a subject by co-administering an anti-PD-1 antibody and fecal material from a donor that is a responder to anti-PD-1 therapy (Figure 3).
Regarding claim 7, 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).
With respect to claim 9 and the limitation wherein the donor has a progression-free survival of at least 36 months, Baruch et al teaches that FMT donors had achieved a complete response for at least 1 year (pg 1, column 2, para 1). Further, 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). Given that Baruch et al teach donors who exhibit a complete response for at least a year, and further given that Gajewski teaches metrics for assessing responsiveness to anti-PD-1 therapy, as determined by RECIST criteria, it would have been obvious to the ordinary artisan to select donors that exhibit durable long-term responses, including PFS of 36 months, to increase likelihood of therapeutic efficacy. In the absence of unexpected results, such a modification would be considered optimization of a known parameter.
Regarding the bacteria limitations of instant claims 10-12, Gajewski identified anti-PD-1 responders and non-responders by assessing relative abundance of differentially abundant taxa of bacteria (see Figure 1A-B); Lachnospiraceae bacterium and Bifidobacterium longum are elevated in responders (see Table 5). Given that Baruch et al teach a method of treating anti-PD-1 refractory melanoma comprising administering an anti-PD-1 antibody and a FMT from a donor that is responsive to anti-PD-1 therapy, and further given that Gajewski identifies the claimed bacteria in anti-PD-1 therapy responsive patients, it would have been obvious to one of ordinary skill in the art that the bacteria composition of the donor would be comprised of the same bacteria, as the donor samples are derived from the same patient population. One would have a reasonable expectation of identifying the specific bacteria of Gajewski in the donor material of Baruch et al.
Regarding the limitation wherein the fecal sample is administered once of instant claim 13, the bacterial formulation of Gajewski is administered in some embodiments as two or more doses or one dose (pg 7, 10). Because Gajewski recognizes that dose number are a result-effective variable and a part of routine optimization, it would have been obvious to a person of ordinary skill in the art to modify the teachings of Baruch et al in view of Gajewski to arrive at the claimed method wherein the fecal sample is administered once. The determination of the number of doses is well within the skill of those skilled artisans. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215,219 (CCPA 1980). It is the examiner’s position that the result-effective variables of dose number was determined by routine optimization by methods that were already known in the art.
Response to Arguments
Applicant’s arguments with respect to the rejection of claims 1-3 and 4-17 under 35 U.S.C. 103 as being obvious over Gajewski have been considered but are moot because the new ground of rejection does not rely on this reference alone as applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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