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 .
Election/Restrictions
Applicant’s election of the species vancomycin in the reply filed on October 4, 2024, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Vancomycin reads on amended claims 1-4, 6-7, 9, 29, and 33.
The elected species vancomycin was searched and prior art was found. The search was not extended in accordance with MPEP § 803.02.
Claim Rejections - 35 USC § 112 - withdrawn
The rejections of claim 10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, and under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, are withdrawn because the claim is cancelled.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-4, 6-7, 9, 29, and 33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that "[w]hile there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure" (see, e.g., MPEP § 2163(I)(B)).
Claim 1 has been amended as follows:
the method comprising administering only one antibiotic composition one time, the antibiotic composition consisting of: i) a pharmaceutically acceptable carrier and ii) one antibiotic
Accordingly, the claim has been amended to a single administration of a single antibiotic, whereas the claims were originally directed to a method comprising administering a single antibiotic, which includes multiple administrations.
The standards for determining compliance with the written description requirement is discussed at MPEP § 2163. Notably, the introduction of claim changes which involve narrowing the claims by introducing elements or limitations which are not supported by the as-filed disclosure is a violation of the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. Here, the issue is whether or not the original disclosure provided support specifically for a single administration of a single antibiotic.
Lack of Express Disclosure
Neither the amended claim nor the amended claim language literally appears in the originally-filed disclosure. Zero examples of the instantly claimed invention literally appear in the originally-filed disclosure. Accordingly, the amended claim scope is not supported by express disclosure in the originally-filed disclosure.
Lack of Implicit or Inherent Support
In the Reply filed January 2, 2026, Applicant identified paragraphs [0042], [0080], [0109], and original claim 7 as providing support for the amended claim scope (Reply filed January 2, 2026 at page 4, first paragraph). However, none of these sections of the specification disclose a single administration of a single antibiotic. Paragraph [0042] describes “mice treated with antibiotic water (cefoxitin, vancomycin, gentamicin and metronidazole)”. This antibiotic water contains multiple antibiotics, not only one. Furthermore, there is no indication that the antibiotic water is administered only once. Paragraph [0080] describes the class of antimicrobial peptides but does not disclose administering a single dose of only one of the antimicrobial peptides. Paragraph [0109] describes “the GI tract was decontaminated with broad spectrum oral antibiotics (vancomycin, gentamicin, metronidazole and cefoxitin) for 2 weeks”. This suggest that multiple antibiotics, not only one, were used for GI tract contamination. Furthermore, there is no indication that “for 2 weeks” means administered only once. Therefore, the specification does not provide inherent or implicit support for the newly amended claim scope.
The dependent claims fail to remedy this issue.
Accordingly, amended claims 1-4, 6-7, 9, 29, and 33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
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.
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 1-4, 6-7, 9, 29, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Van den Brink et al. (WO 2016/086161 A1) in view of Isaac et al. (“Short- and long-term effects of oral vancomycin on the human intestinal microbiota,” J Antimicrob Chemother 2017; 72: 128–136).
Van den Brink et al. teach a method of reducing the risk of graft versus host disease (GVHD) comprising administering the elected species vancomycin by an oral route in combination with ampicillin to a transplant recipient prior to the transplant recipient receiving pre-transplant conditioning therapy (paragraph [00102]):
C57BL/6 mice purchased from The Jackson Laboratory (Bar Harbor, Maine) were treated with oral vancomycin and ampicillin. Following decontamination, mice were housed in autoclaved conditions (caging, bedding, water and food) to eliminate nearly all endogenous Clostridia present within the flora of mice. Mice were then treated by gavage with either a liquid suspension of cultured Enterococcus faecalis as a control, or a Blautia isolate. Mice were then exposed to a myeloablative dose of total body irradiation (TBI, 1 1 Gy) and then transplanted by intravenous injection with bone marrow and purified T cells from fully MHC-mismatched B10.BR mice (H2k into H2b). Effects on intestinal pathology and overall survival were evaluated as described. Mice colonized by Blautia, compared to those harboring Enterococcus, were protected from GVHD, with improved survival (Figure 9).
The mice in the reference were treated orally with a two day course of vancomycin, a two day course of ampicillin, then inoculated five and seven days later with Blautia or Enterococcus of murine origin, and then two weeks later irradiated and transplanted with B10.BR bone marrow and T cells (paragraph [0036]). The mice receiving vancomycin, ampicillin, and Blautia experienced protection from GVHD.
Van den Brink et al. do not teach that the method is limited to administering only oral vancomycin in the absence of ampicillin.
It would have been obvious to perform the protocol with three different treatment groups: only vancomycin, only ampicillin, and the combination of vancomycin and ampicillin. One of ordinary skill in the art would have been motivated to do so to identify the minimal treatment needed for decontamination. There would have been a reasonable expectation of success given that the protocol is taught in the art and modification of antibiotic administration is within the ordinary skill in the art. In addition, Isaac et al. report that vancomycin depletes most bacterial operational taxonomic units found in the intestinal tract (abstract).
There is no evidence on record, either in the original specification nor in a declaration, that oral administration of a composition consisting of vancomycin exhibits results that are unexpected in view of the prior art teaching the combination of vancomycin and ampicillin.
With respect to claims 2-4, Van den Brink et al. teaches that the vancomycin is administered prior to the conditioning therapy.
MPEP § 2144.05(I) states: In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). In the instant case, the prior art teaches administration of vancomycin before conditioning therapy, which is a range that overlaps with the claimed ranges of at least three days prior, at least seven days prior, and at least two weeks prior.
In addition, MPEP § 2144.05(II)(A) states: "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In the instant case, the prior art teaches that the time interval between vancomycin administration and conditioning therapy is sufficient for eliminating endogenous Clostridia present within the flora of the subject. It would have been obvious to optimize the time interval using routine optimization to achieve this disclosed effect.
With respect to claims 6-7 and 33, Van den Brink et al. teaches vancomycin, a broad-spectrum antibiotic
With respect to claim 9, Van den Brink et al. teaches administering a probiotic, specifically a liquid suspension of cultured Enterococcus faecalis, or a Blautia isolate, after administration of the vancomycin and before the condition therapy.
Regarding the functional limitations in claims 1 and 29, Van den Brink et al. is silent on the effect of the vancomycin on the transplant recipient’s gut microbiome and MHC class II expression on intestinal epithelial cells and on all of the functional limitations of these claims. Because the prior art teaches the same composition (elective species vancomycin) administered to the same patients (transplant recipients) at the same time (prior to pre-transplant conditioning therapy), the prior art inherently achieves these claimed effects.
Response to Arguments
Applicant's arguments filed January 2, 2026, have been fully considered but they are not persuasive.
First, Applicant refers to paragraphs [0053]-[0060], [0109] and Figures 3 and 7 of the specification for evidence that the claimed invention is based on one antibiotic alone being sufficient and critical to achieve targeted modulation of the microbiome. However, none of these paragraphs discloses a single, one time administration of a single antibiotic, as required by the amended claims.
Second, Applicant traverses the rejection on the grounds that because Van den Brink teaches a multi-agent therapy that functions by a different mechanism, and that Isaac teaches protentional negative side effects, there was no motivation to combine the references to arrive at a single-agent, mechanism-based method as claimed. This argument is not persuasive. POSITA would be motivated to begin with Van den Brink’s teaching of the combination of vancomycin and ampicillin for decontamination, and to identify the minimal treatment needed for decontamination. The logical application starting from Van den Brink would be to test vancomycin alone, and ampicillin alone, and to compare these single treatments to the combination. Because Isaac et al. report that vancomycin depletes most bacterial operational taxonomic units found in the intestinal tract (abstract), there was a reasonable expectation that the single therapy of vancomycin would be successful. There is no evidence on record, either in the original specification nor in a declaration, that oral administration of a composition consisting of vancomycin exhibits results that are unexpected in view of the prior art teaching the combination of vancomycin and ampicillin.
In response to applicant's argument that Van den Brink teaches that the antibiotics modulate SCFA/Treg rather than underlying effect in the claimed invention, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Third, Applicant traverses the rejection on the grounds that the claimed time interval of administration is not routine optimization. This argument is not persuasive because Applicants have not rebutted the prima facie case of obviousness by showing the criticality of the claimed administration step of a single, one time administration of a single antibiotic. There is no evidence that the claimed invention was disclosed in the specification let alone that it achieves an unexpected result relative to the prior art.
For these reasons, the rejection is maintained.
Conclusion
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 CHRISTINA MARCHETTI BRADLEY whose telephone number is (571)272-9044. The examiner can normally be reached Monday-Friday, 7 am - 3 pm.
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/CHRISTINA BRADLEY/Primary Examiner, Art Unit 1654