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
This office action is a response to applicant’s communication submitted May 21, 2026, wherein claims 61, 64, 65, and 68-79 are amended and claims 62, 63, 66, 67, and 80 are canceled. This application is a national stage application of PCT/US2022/012120, filed January 12, 2022, which claims benefit of provisional applications 63/135549, filed March 24, 2021, and 63/136469, filed January 12, 2021.
Claims 61, 64, 65, and 68-79, are pending in this application.
Claims 61, 64, 65, and 68-79 as amended are examined on the merits herein.
Claim Interpretation
Independent claims 61, 72, and 77 refer to synthetic human milk oligosaccharides. P. 115 paragraph 330 of the specification defines “synthetic human milk oligosaccharide” as referring to an oligosaccharide not isolated from milk. Examples given include oligosaccharides made by chemical synthesis or fermentation by microorganisms. However, this definition does not provide any actual structural limitation that would differentiate an oligosaccharide obtained from milk from the same oligosaccharide obtained from some other source. Therefore for the sake of this office action any human milk oligosaccharide will be interpreted as falling within the scope of this limitation.
Withdrawn Rejections
Applicant’s amendment, submitted May 21, 2026, with respect to the rejection of claims 61-80 under 35 USC 112(b) for indefinitely referring to a subject who has been previously administered another therapy, has been fully considered and found to be persuasive as remove the rejection as the claims have been amended to explicitly claim both the initial colonization step and the maintenance phase. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted May 21, 2026, with respect to the rejection of claim 67 under 35 USC 112(b) for indefinitely reciting steps which could be reasonably be interpreted either as process or product-by-process steps, has been fully considered and found to be persuasive to remove the rejection as claim 67 has been canceled.
Applicant’s amendment, submitted May 21, 2026, with respect to the rejection of claims 63, 66-68, 72, 73, and 78-80 under 35 USC 112(b) for indefinitely referring to a broad range followed by a narrow range, has been fully considered and found to be persuasive as remove the rejection as the claims have been amended to explicitly claim both the initial colonization step and the maintenance phase. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted May 21, 2026, with respect to the rejection as claims 61, 62, and 65-70 under 35 USC 102(a)(1) for being anticipated by Kyle et al., has been fully considered and found to be persuasive to remove the rejection as the claims have been amended to require a specific dose and length of administration for the maintenance phase. Therefore the rejection nis withdrawn.
Applicant’s amendment, submitted May 21, 2026, with respect to the rejection of claims 61, 62, and 65-71 for claiming the same invention as claims 88 and 92-95 of US application 18/021043, has been fully considered and found to be persuasive to remove the rejection as the claims of ‘043 do not claim or suggest a method comprising separate colonization and maintenance steps or a specific dose and length of administration. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted May 21, 2026, with respect to the rejection of claims 61, 62, and 65-71 for claiming the same invention as claims 88 and 92-95 of US application 19/259517, has been fully considered and found to be persuasive to remove the rejection as the claims of ‘517 do not claim or suggest a method comprising separate colonization and maintenance steps or a specific dose and length of administration. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted Mat 21, 2026, with respect to the rejection of claims 61, 62, and 65-71 for claiming the same invention as claims 1-11 of U.S. Patent No. 12364721, has been fully considered and found to be persuasive to remove the rejection as the claims of ‘721 do not claim or suggest a method comprising separate colonization and maintenance steps or a specific dose and length of administration. Therefore the rejection is withdrawn.
The following rejections of record in the previous action are maintained:
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.
Claims 72 and 74-76 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kyle et al. (PCT international publication WO2017/156550, Reference FP47 included with 2/14/2024 PTO-1449)
Independent claim 72 is directed to a similar method of treating a subject, wherein the subject is described as being in need of treatment for one of a number of disorders including dysbiosis, inflammation, or infection. Dependent claims 74-76 further define these conditions as including irritable bowel syndrome, inflammatory bowel disease, and bacterial infections.
Kyle et al. discloses using probiotic microorganisms for which mammalian milk oligosaccharides serve as a selective energy source as a treatment for conditions including IBS, Crohn’s disease, ulcerative colitis, and intestinal bacterial infections. (p. 3 paragraph 9) In particular this method comprises administering a complex carbohydrate from a mammalian milk source and bifidobacteria which internalize the MMO. (p. 3 paragraph 10) The MMO is additionally described as being produced synthetically or as being purified or isolated from natural sources. In a particular embodiment the bifidobacterium is B. longum subsp infantis. (p. 8 paragraph 24) The MMO can be a human milk oligosaccharide. (p. 6 paragraph 20) The subject can be an adult human. (p. 10 paragraph 30) Kyle et al. further discloses that in one embodiment the process comprises administering a composition comprising the bifidobacteria and the oligosaccharide component for one period of time, followed by administering the oligosaccharide without the bacteria for a second period of time, to keep the bifidobacteria colonized. (p. 14 paragraph 43) Such a process is reasonably considered to comprise maintaining engraftment of the bifidobacteria in a subject who has previously been administered a synbiotic composition as recited in base claim 61, as well as a method of treating disease by administering said composition to a subject treated in this manner according to claims 72 and 74-76.
While base claim 72 as presently pending describes the process of administering step as comprising administering a synthetic oligosaccharide and the prior treatment as administering a human milk permeate comprising human milk oligosaccharides, as discussed under the section “claim interpretation,” there is no necessary structural difference between natural and synthetic human milk oligosaccharides. Therefore the limitations of the present claim will be met regardless of the actual method by which the two HMO compositions were obtained.
For these reason Kyle et al. anticipates the present claims.
Response to Arguments: Applicant’s arguments, submitted May 21, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. Specifically, regarding independent claim 72 and its dependent claims, Applicant argues that claim 72 has been amended to incorporate the subject matter of former claim 64. However, a review of the amendment submitted 5/21/2026 indicates that in fact the amendment to claim 72 merely lists specific saccharides and does not incorporate the subject matter of claim 64, which specifies a particular dosage of saccharides. Therefore this argument is moot and the claims is maintained.
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 61-66 and 68-76 are rejected under 35 U.S.C. 103 as being unpatentable over Kyle et al. (PCT international publication WO2017/156550, Reference FP47 included with 2/14/2024 PTO-1449)
Independent claim 61 is directed to a process for maintaining engraftment of B. longum subsp infantis (B. infantis) in an adult subject comprising a colonization step wherein the bacterium is coadministered with concentrated human milk permeate, and a maintenance phase in which at least one human milk oligosaccharide is administered without further administration of the bacterium. Independent claim 72 is directed to a similar method of treating a subject, wherein the subject is described as being in need of treatment for one of a number of disorders including dysbiosis, inflammation, or infection. Dependent claims 74-76 further define these conditions as including irritable bowel syndrome, inflammatory bowel disease, and bacterial infections.
Kyle et al. discloses using probiotic microorganisms for which mammalian milk oligosaccharides serve as a selective energy source as a treatment for conditions including IBS, Crohn’s disease, ulcerative colitis, and intestinal bacterial infections. (p. 3 paragraph 9) In particular this method comprises administering a complex carbohydrate from a mammalian milk source and bifidobacteria which internalize the MMO. (p. 3 paragraph 10) The MMO is additionally described as being produced synthetically or as being purified or isolated from natural sources. P. 4 paragraph 10 of Kyle describes the MMO as comprising thirteen different oligosaccharides and mentions oligosaccharides recited in present claims 61 and 72. In a particular embodiment the bifidobacterium is B. longum subsp infantis. (p. 8 paragraph 24) The MMO can be a human milk oligosaccharide. (p. 6 paragraph 20) The subject can be an adult human. (p. 10 paragraph 30)
Kyle et al. further discloses that in one embodiment the process comprises administering a composition comprising the bifidobacteria and the oligosaccharide component for one period of time, followed by administering the oligosaccharide without the bacteria for a second period of time, to keep the bifidobacteria colonized. (p. 14 paragraph 43) Such a process is reasonably considered to comprise colonization and maintenance phases as recited in base claim 61, as well as a method of treating disease by administering said composition to a subject treated in this manner according to claims 72 and 74-76.
While base claims 61 and 72 as presently pending describe the first step as comprising administering a human milk permeate and the second step as comprising administering a synthetic oligosaccharide, as discussed under the section “claim interpretation,” there is no necessary structural difference between natural and synthetic human milk oligosaccharides. Therefore the limitations of the present claim will be met regardless of the actual method by which the two HMO compositions were obtained.
Regarding claims 65 and 68-70, these dependent claims specify properties of the process of previously administering the synbiotic composition which in the broadest reasonable interpretation is not an actually required process step, and therefore do not necessarily distinguish the subject from the subject described by Kyle et al.
Kyle et al. does not specifically describe the claimed doses, frequency, or length of administration recited in independent claims 61 and 72. However, Kyle describes doses and administration schedules for the bacteria and MMO which overlap the claimed amounts. (p. 9 paragraph 27, p. 10 paragraph 29, p. 11 paragraph 33) One of ordinary skill in the art would therefore have regarded these parameters as result-effective variables and would have found it to be obvious to determine the appropriate dose and schedule of administration within the broad disclosure described by Kyle et al.
Furthermore with respect to the specific oligosaccharides recited in the independent claims, Thurl et al. (Reference of record in previous action) evidences that all of the oligosaccharides recited in this claim occur in human milk. (See p. 1266 table 4, p. 1267 table 5, p. 1268 table 7) Therefore the human milk permeate described by Kyle et al. would reasonably be considered to include all of these oligosaccharides.
Therefore the invention taken as a whole is prima facie obvious.
Response to Arguments: Applicant’s arguments, submitted May 21, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant argues that the invention is based on the surprising finding that a human milk permeate comprising all of the various recited oligosaccharides is surprisingly effective for promoting the initial engraftment of B. longum subsp. Infantis, but that it is not necessary for maintaining engraftment, and a composition comprising fewer oligosaccharides is sufficient. This amounts to an argument based on a finding of unexpected results.
In order to support such an argument, objective evidence must be provided demonstrating the unexpected result. According to table E1 in example 2 of the specification, subjects were administered HMO as human milk permeate for 14 days, with B. infantis probiotic administered for the first seven of those days. This experimental method involves separate colonization and maintenance phases as claimed but uses the same human milk permeate in both steps. Therefore it does not address the question of whether a maintenance composition using fewer than the full number of human milk oligosaccharides would be equally effective.
Example 3 in the specification describes a study which is more relevant to the claimed process, comparing administration of probiotic for 14 days and permeate for 28 days with a method wherein permeate is administered only for nine days before switching to a mixture of two oligosaccharides. (2’-FL and LNnT, see table E4 on p. 120) However, the specification describes the experimental protocol but does not describe the results of the study, thereby failing to provide objective evidence of any unexpected result.
Additionally, even if such evidence were provided and showed evidence of a surprising result, such evidence would not be commensurate in scope with the claims as currently pending. In particular, while example 3 in the specification describes the synthetic HMO composition used in the maintenance phase as comprising the two synthetic HMOs 2’FL and LNnT, the maintenance phase described in the present claims comprises one or more HMOs selected from eight specific HMOs, and optionally comprising any number of additional HMOs. While this genus encompasses the specific two oligosaccharides described in the examples, it does not require them, nor is it limited to these two. In particular, the exact same combination of oligosaccharides could infringe both the first (permeate) step and the second (synthetic) step. Furthermore the description of the second maintenance phase never specifically excludes continuing administration of the B. infantis probiotic. All of these differences indicate that example 3 would not be exemplary of the full scope of processes recited in the claims.
For these reasons the rejection is deemed proper and maintained.
Claims 77-79 are rejected under 35 U.S.C. 103 as being unpatentable over Kyle et al. as applied
to claims 61-66 and 68-71 above, and further in view of Noor et al. (Reference of record in previous action)
The disclosure of Kyle et al. is discussed above. Kyle et al. does not disclose a method wherein the patient being treated has received or will receive an allogenic stem cell transplant.
Noor et al. discloses that patients undergoing allogenic human stem cell transplant (allo-HSCT) after treatment of hematological malignancies often develop graft-versus-host disease, or GVHD. (p. 408 left column third paragraph) This is found to be associated with disruptions to gut microbiota. (p. 408 right column first and second paragraphs) Modulation of gut microbiota is seen as a way to alleviate and prevent GVHD. (p. 409 right column first paragraph) Probiotics and prebiotics are additionally describes as therapeutics to alleviate GVHD. (p. 410 left column third paragraph – right column second paragraph)
It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the therapeutic intervention described by Kyle et al. as a treatment or prevention for GVHD in a patient receiving allo-HSCT.
In particular, one of ordinary skill in the art would have seen the description of the effect of Kyle’s synbiotics on mucosal healing and susceptibility to infections (see paragraphs 9-10 of Kyle) and Noor’s description of the use of probiotics and prebiotics to prevent infections and improve intestinal health in GVHD, as both suggesting that Kyle’s therapy would be useful in this subset of patients.
Regarding claim 79, Noor further describes the use of antibiotics in patients suffering from or at risk for GVHD. (p. 409 left column last paragraph – p. 410 right column first paragraph) This would suggest to one of ordinary skill in the art to additionally administer antibiotic therapy. Regarding the specific dosages or lengths of treatment recited in claims 78-79, as discussed previously Kyle describes doses and administration schedules for the bacteria and MMO which overlap the claimed amounts. (p. 9 paragraph 27, p. 10 paragraph 29, p. 11 paragraph 33) One of ordinary skill in the art would therefore have regarded these parameters as result-effective variables and would have found it to be obvious to determine the appropriate dose and schedule of administration within the broad disclosure described by Kyle et al.
Therefore the invention taken as a whole is prima facie obvious.
Response to Arguments: Applicant’s arguments, submitted May 21, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant’s arguments are the same as those made with respect to the rejection over Kyle et al. alone, and are found to be not persuasive for the same reasons. Therefore the rejection is deemed proper and maintained.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 72 and 74-76 are provisionally rejected on the ground of nonstatutory double
patenting as being unpatentable over claims 79, 84 and 92-25 of copending Application No. 18/021043 (reference application, US pre-grant publication 2024/0139222, cited in PTO-892, herein referred to as ‘043). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘043 render the present claims obvious.
Specifically, claim 79 of ‘043 claims a method for treating a subject who has undergone bacteriotherapy, comprising administering to the patient a mixture of prebiotic oligosaccharides and a probiotic microorganism. Dependent claim 84 defines the probiotic microorganism as B. longum subsp infantis. Dependent claim 93 further describes the prebiotic mixture as including oligosaccharides falling within those recited in present claim 62. Dependent claim 87 describes the disease being treated as selected from a list falling within the scope of present claims 72 and 74-76. While the claims of ‘043 do not specifically describe administering two separate colonization and maintenance phases, it is noted that the present claims refer to a method “comprising administering to the subject one or more synthetic human milk oligosaccharides,” but do not exclude co-administering a probiotic. Therefore administering the synbiotic described in claim 79 of ‘043 over an extended period (i.e. two or more times” would infringe the claimed method as some of the doses could be regarded as colonization doses and some as maintenance doses. Still further as discussed under 35 USC 102 and 103, there is no necessary difference between a patient treated with synthetic HMO as opposed to human milk permeate, these limitations do not serve to differentiate the present claims form those of ‘043. Since one of ordinary skill in the art would have naturally administered the therapy over as long a period of time as necessary, doing so would render the present claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Argument: Applicant’s arguments, submitted May 21, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant argues that claim 72 has been amended to incorporate the subject matter of claim 64. However, a review of the amendment submitted 5/21/2026 indicates that in fact the amendment to claim 72 merely lists specific saccharides and does not incorporate the subject matter of claim 64, which specifies a particular dosage of saccharides. Therefore this argument is moot and the claims is maintained.
Claims 72 and 74-76 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-10, and 27 of copending Application No. 19/259517 (reference application, unpublished, cited in PTO-892, herein referred to as ‘517). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘043 render the present claims obvious.
Specifically, claim 1 of ‘517 claims a method for treating a subject suffering from one of a number of disorders, comprising administering to the patient a mixture of prebiotic oligosaccharides and a probiotic microorganism. Dependent claim 5 defines the probiotic microorganism as B. longum subsp infantis. Dependent claim 27 further describes the prebiotic mixture as including oligosaccharides falling within those recited in present claim 62. Dependent claims 9-10 describe the disease being treated as selected from a list falling within the scope of present claims 72 and 74-76. While the claims of ‘517 do not specifically describe administering a HMO composition to a subject who previously received the synbiotic composition, it is noted that the present claims refer to a method “comprising administering to the subject one or more synthetic human milk oligosaccharides,” but do not exclude co-administering a probiotic. Therefore administering the synbiotic described in claim 79 of ‘517 over an extended period (i.e. two or more times) would infringe the claimed method as some of the doses could be regarded as colonization doses and some as maintenance doses. Still further as discussed under 35 USC 103, there is no necessary difference between a patient treated with synthetic HMO as opposed to human milk permeate, these limitations do not serve to differentiate the present claims form those of ‘517. Since one of ordinary skill in the art would have naturally administered the therapy over as long a period of time as necessary, doing so would render the present claims obvious.
Still further as discussed under 35 USC 102 and 103, there is no necessary difference between a patient treated with synthetic HMO as opposed to human milk permeate, these limitations do not serve to differentiate the present claims form those of ‘517. Since one of ordinary skill in the art would have naturally administered the therapy over as long a period of time as necessary, doing so would render the present claims obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Argument: Applicant’s arguments, submitted May 21, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant argues that claim 72 has been amended to incorporate the subject matter of claim 64. However, a review of the amendment submitted 5/21/2026 indicates that in fact the amendment to claim 72 merely lists specific saccharides and does not incorporate the subject matter of claim 64, which specifies a particular dosage of saccharides. Therefore this argument is moot and the claims is maintained.
Conclusion
No claims are allowed in this action. THIS ACTION IS MADE FINAL. 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 ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 7/16/2026
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