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
Claims 1, 5-11 and 23 are pending.
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, or §365(c) is acknowledged. As noted in the Non-Final Office Action mailed 16 June 2025, Applicant has claimed the benefit of the filing date of the prior application, and designates the instant application as a "CON" of 15/603,916.
Claims 1, 5-11 and 23 have the effective filing date of 25 November 2014.
Drawings
One of the objections to the drawings received 15 March 2024, cited in the Non-Final Office Action mailed on 15 June 2025, is withdrawn in view of Applicants' amendment received 16 December 2025.
Replacement drawings were received on 16 December 2025. These drawings overcome the objection with regard to Figure 17D and Figure 17E being presented on more than one page; i.e., as 'continued' figures.
However, these drawings are in color.
Therefore, the drawings received on 15 March 2024 and 16 December 2025 are objected to.
All of the drawings except for Fig. 1B, Fig. 14A-D and Fig. 16A are in color or contain colored markings.
Applicant filed a petition under 37 CFR 1.84(a)(2) to accept color drawings on 16 December 2025. However, this petition was DISMISSED on 27 January 2026.
Color photographs and color drawings are not accepted unless a petition filed under 37 CFR 1.84(a)(2) is granted (MPEP 608.01(f)). Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), three sets of color drawings or color photographs, as appropriate, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification: The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2) and MPEP 608.02 (VIII). Note that the requirement for three sets of color drawings under 37 CFR 1.84(a)(2)(ii) is not applicable to color drawings submitted via EFS-Web. Therefore, only one set of such color drawings is necessary when filing via EFS-Web.
After review by appropriate personnel the petition will be granted or dismissed accordingly.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) (and/or appropriate amendment to the specification) 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.
Claim Objections
Claim 23 is objected to because of the following informalities:
Claim 23 recites: "The therapeutic composition of claim 1, wherein the one or more purified populations of a bacteria...", which should read: "The therapeutic composition of claim 1, wherein the one or more purified populations of bacteria..."
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 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 of this title, 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, 5-7, 10-11 and 23 are rejected under 35 U.S.C. §103 as being unpatentable over Allen-Vercoe et al. (WO 2013/037068 A1) in view of Pajon et al. ((2010) NCBI Blast search (SEQ ID NO.: 1); Downloaded on: 08 May 2025; pp. 1-4).
The term "therapeutic" and the phrase "for prophylaxis and/or treatment of graft versus host disease (GVHD) following bone marrow (BMT) or hematopoietic stem cell transplant (HSCT)" recited in claim 1 are considered to be intended use terminology. The intended use phrase is also recited in claim 23. The intended use language does not limit the scope of the claimed subject matter (MPEP 2111.02 (I)(II).
Regarding claims 1and 23, Allen-Vercoe et al. shows a synthetic stool preparation and methods of use thereof for treating disorders associated with dysbiosis of the gastrointestinal tract (pg. 1, para. 2). In another embodiment, synthetic stool preparations comprise only, or comprise predominantly (i.e., are "rich in") bacterial strains of the order Clostridiales, e.g., bacterial strains of the family Catabacteriaceae, Clostridiaceae, Erisipelotrichaceae, Eubacteriaceae, Lachnospiraceae, or Ruminococcaceae (pg. 24, para. 3). The described synthetic stool preparations comprise a mixture of purified intestinal bacterial cultures (pg. 14, para. 1). Therapeutic use of the synthetic stool preparations is described (pg. 14, para. 3).
Further regarding claim 1, pertaining to Ruminococcus obeum [elected species], Allen-Vercoe et al. shows that the described synthetic stool preparation comprises a mixture of bacterial strains, wherein the mixture comprises at least one bacterial strain selected from a group which includes, minimally, Ruminococcus obeum (pg. 4, para. 2). An embodiment of the synthetic stool preparation includes two different strains of R. obeum- 2MRS and 11FM1 (pg. 19, cont. Table 2).
Allen-Vercoe et al. does not show: the Ruminococcus obeum comprises a 16S rDNA sequence with 98% to 100% identity to the nucleotide sequence set forth in SEQ ID NO.: 1.
Pajon et al. shows a strain of Ruminococcus obeum which contains the same nucleotide sequence as represented by SEQ ID NO.: 1. The Ruminococcus obeum strain A2-162 genome was directly submitted by Pajon et al. on 23 March 2010 to the Sanger Institute, Wellcome Trust Genome Campus, Cambridge UK (pg. 3). That is, the deposited sequence was made known to the general public via recognition by the NIH/NLM (aka Blautia obeum) (pg. 4). An NCBI Blast search for the 16S rDNA nucleotide sequence of SEQ ID NO.: 1 shows a DNA sequence representing the genome of a Ruminococcus obeum strain A2-162 (locus FP929054), which contains a 16S rDNA sequence which is 100% identical to instant SEQ ID NO.: 1 (pp. 1-2).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified the therapeutic composition for prophylaxis and/or treatment of GVHD following BMT or HSCT comprising one or more purified populations of bacteria of the order Clostridiales, including Ruminococcus obeum, as shown by Allen-Vercoe et al., by including in the composition R. obeum bacteria comprising the 16S rDNA nucleotide sequence of SEQ ID NO.: 1 [species election], as shown by Pajon et al., with a reasonable expectation of success. It would have been obvious to one of ordinary skill in the art to have included the R. obeum strain A2-162, shown by Pajon et al., in the compositions shown by Allen-Vercoe et al., with the reasonably predictable expectation that the compositions would have been effective for their intended therapeutic use (MPEP 2143 (I)(G)).
One of ordinary skill in the art would have been motivated to have made those modifications, because including at least one strain of a specific species (e.g., Ruminococcus obeum) in a composition intended to be used for therapeutic purposes would be improved in the event that the different strains have some complementary biochemical properties that contribute to the overall efficacy of the composition.
Regarding claim 5, Allen-Vercoe et al. shows that the synthetic stool preparation may be freeze-dried (pg. 6, para. 4).
Regarding claims 6 and 7, the synthetic stool preparation of the invention comprises some or all of the 31 bacterial strains listed in Table 2. In the synthetic stool preparation, amounts were adjusted to give, on average, a total cell count of ~4 to 7 x 109 Colony Forming Units/ml (pg. 18, para. 1 and Table 2). [Table 2 includes Ruminococcus obeum (pg. 19, cont. Table 2).]
Regarding claim 10, in other embodiments, the synthetic stool preparation is adapted for administration orally (pg. 6, para. 4).
Regarding claim 11, in an embodiment, the synthetic stool preparation is adapted for administration via rectal enema by the colonoscopic route (pg. 6, para. 4).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claims 8 and 9 are rejected under 35 U.S.C. §103 as being unpatentable over Allen-Vercoe et al. in view of Pajon et al., as applied to claims 1, 5-7, 10-11 and 23 above, and further in view of McKenzie et al. (WO 2014/121302 A2).
Allen-Vercoe et al. in view of Pajon et al. do not show: the bacteria are present in a dose of 106 to 108 CFUs [Claim 8]; and said bacteria ferment an oligosaccharide selected from xylose, raffinose, cellobiose or melezitose [Claim 9].
McKenzie et al. shows therapeutic compositions containing nonpathogenic, germination-competent bacterial spores, for the prevention, control, and treatment of gastrointestinal diseases, disorders and conditions and for general nutritional health (pg. 2, para. [009]). Preferred bacterial genera include, minimally, Clostridiales and Ruminococcus (pg. 26, para. [0116] [nexus to Allen-Vercoe et al.- composition comprising one more populations of Clostridiales bacteria, including Ruminococcus]). The bacterial composition comprises at least one and preferably more than one of the following from a group which includes, minimally, Ruminococcus obeum (pg. 30, para. [0132] thru pg. 31, cont. para. [0132] [nexus to Allen-Vercoe et al.- composition containing R. obeum]).
Regarding claim 8, the composition is formulated such that a single oral dose contains at least about 1x104 colony forming units of the bacterial spores, and a single oral dose will typically contain about 1x104, 1x105, 1x106, 1x107, 1x108, 1x109, 1x1010, 1x1011, 1x1012, 1x1013, 1x1014, 1x1015, or greater than 1x1015 CFUs of the bacterial spores (pg. 42, para. [0175]).
Regarding claim 9, McKenzie et al. shows that, in some embodiments, the composition comprises at least one carbohydrate. A carbohydrate can be a monosaccharide, a disaccharide, trisaccharide, oligosaccharide, or polysaccharide. The most basic carbohydrate is a monosaccharide, such as, minimally, xylose. Exemplary disaccharides include, minimally, cellobiose. Typically, an oligosaccharide includes between three and six monosaccharide units (e.g., raffinose) (pg. 65, para. [0244]).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified the therapeutic composition for prophylaxis and/or treatment of GVHD following BMT or HSCT comprising one or more purified populations of bacteria of the order Clostridiales, including Ruminococcus, as shown by Allen-Vercoe et al. in view of Pajon et al., as applied to claims 1, 5-7, 10-11 and 23 above, by formulating the composition in which the bacteria are present in a dose of 106 to 108 CFUs [Claim 8], as shown by McKenzie et al., with a reasonable expectation of success, because McKenzie et al. shows a therapeutic composition comprising one or more purified bacteria of the order Clostridiales, including Ruminococcus, which is the composition shown by Allen-Vercoe et al. (MPEP 2143 (I)(G)). Instant claim 5 describes the bacteria in the composition as, minimally, bacterial spores.
Even in the absence of McKenzie et al., it would have been obvious to have formulated the composition to contain 106 to 108 CFUs of bacteria, because Allen-Vercoe et al. shows that the composition is formulated to contain ~4 to 7 x 109 Colony Forming Units/ml. Therefore, one of ordinary skill in the art of formulating microbial compositions for treating gastrointestinal dysbiosis would have used routine optimization to have determined the optimal amount of bacteria (e.g., 106 to 108 CFUs) in the compositions shown by Allen-Vercoe et al. depending on, e.g., the type of dysbiosis, the number of different bacterial species in the composition, the administration regimen etc., barring a showing of criticality for the specific limitation (MPEP 2144.05 (II)(III)).
It would have been further obvious to have selected bacteria that ferment an oligosaccharide selected from xylose, raffinose or cellobiose [Claim 9], as shown by McKenzie et al., with a reasonable expectation of success, because McKenzie et al. shows that described compositions may include oligosaccharides, such as xylose, raffinose or cellobiose, from which it would be understood by one of ordinary skill in the art that, therefore, said oligosaccharides would be fermentable by the bacteria in the described compositions (MPEP 2143 (I)(G)).
In addition, Allen-Vercoe et al. teaches that the synthetic stool preparation further comprises a prebiotic. Any prebiotic known in the art may be used. Non-limiting examples of prebiotics include oligosaccharides (pg. 38, para. 4). Therefore, even in the absence of McKenzie et al., it would have been obvious to have included any of xylose, raffinose, cellobiose or melezitose in the compositions shown by Allen-Vercoe et al., barring a showing of criticality for the specific limitations, because these sugars are described as oligosaccharides in instant claim 9, which are taught by Allen-Vercoe et al. (MPEP 2143 (I)(G)).
One of ordinary skill in the art would have been motivated to have made those modifications, because Allen-Vercoe et al. teaches that a prebiotic may provide a bolus of nutrients for the strains in the synthetic stool preparation to assist their early growth after administration to the patient (pg. 38, para. 4). Therefore, one of ordinary skill in the art of developing therapeutic microbial/probiotic compositions would have included bacteria which are able to ferment prebiotic oligosaccharides- and, then, included said oligosaccharides in the compositions- because the oligosaccharide sugars would aid in promoting the fast growth of the bacteria.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Response to Arguments
Applicant’s arguments, pp. 11-13, filed 16 December 2025, with respect to the prior art references cited in the 35 U.S.C. §103 rejections, have been fully considered, but they are not persuasive.
1. Applicant remarks (pg. 12, para. 3), that although Allen-Vercoe and McKenzie disclose Ruminococcus obeum, there is no disclosure or suggestion in either reference that a Ruminococcus obeum strain having the 16S rDNA sequence set forth in SEQ ID NO: 1 can be used in a therapeutic composition. Allen-Vercoe discloses two Ruminococcus obeum strains recited as "2 MRS" and" 11 FMl" and McKenzie discloses that Ruminococcus obeum strain associated with Accession No. AY169419 and both do not disclose or suggest a Ruminococcus obeum strain having the 16S rDNA sequence set forth in SEQ ID NO: 1. Pajon is silent with respect to the use of the Ruminococcus obeum strain having the 16S rDNA sequence set forth in SEQ ID NO: 1 in a therapeutic composition. It is the instant application that discloses in Table 1 that a Ruminococcus obeum strain having the 16S rDNA sequence set forth in SEQ ID NO: 1 is associated
with reduced risk or incidence of GVHD in a patient and that such a strain can be used in a therapeutic composition.
However, in response to Applicant, Allen-Vercoe et al. shows that an embodiment of the described synthetic stool preparation includes Ruminococcus obeum bacteria. The synthetic stool preparation is used in methods for treating disorders associated with dysbiosis of the gastrointestinal tract (see 103 rejection above). That is, the preparation or composition has a therapeutic use. Dysbiosis of the gastrointestinal tract (GI) could include graft versus host disease (GVHD) which is characterized by selective damage to the liver, skin, mucosa and GI tract. (However, treatment of GVHD is considered to be an intended use and does not limit the instantly-claimed subject matter.)
Further in response to Applicant, although Pajon et al. does not describe a therapeutic use for Ruminococcus obeum strain A2-162, it would have been obvious to have included this strain in the therapeutic compositions shown by Allen-Vercoe et al., because these compositions may comprise at least one R. obeum strain (see 103 rejection above). Applicant is reminded that the Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether or not Applicants' strain differs, and if so to what extent, from the strains discussed in the references. Accordingly, it has been established that the prior art strains, which have the same genus and species classification and share the property of being able to be included in a therapeutic composition demonstrate a reasonable probability that it is substantially identical to the strain as claimed. Therefore, the burden of establishing novelty or non-obviousness by objective evidence is shifted to Applicants.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHARON M PAPCIAK whose telephone number is (571)272-6235. The examiner can normally be reached M-F 8:30am-5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/SMP/Examiner, Art Unit 1657