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 application is a national stage application of PCT/US2022/012120, filed January 12, 2022, which claims benefit of provisional applications 63/165549, filed March 24, 3031, and 63/136469, filed January 12, 2021. Claims 61-80 are pending in this application and examined on the merits herein. Applicant’s preliminary amendment submitted March 13, 2024 is acknowledged wherein claims 1-60 are canceled and new claims 61-80 are introduced.
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.
Claim Objections
Claim 65 is objected to because of the following informalities: This claim refers to administering a probiotic organism in an amount of at least 1x108 CFU per day. This appears to be a typographical error, and the appropriate amount is believed to be 1x108 CFU per day. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 61-80 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.
Base claims 61, 72, and 77 all refer to a process step involving administering a therapeutic agent to a subject described as one “who has previously been administered” a particular therapy. Because this limitation is not phrased as an explicit process step, it is unclear whether the claims are written so as to require an additional process step of administering the probiotic microorganism and milk permeate to be performed first before the step of “administering to the subject one or more synthetic human milk oligosaccharides.” Therefore the claims are indefinite.
Dependent claim 67 depends from base claim 61, which claims a process involving a step of administering a therapeutic agent to a subject. Claim 67 then describes the concentrated human milk permeate as being “obtained from human milk permeate,” and furthermore describes several steps including ultrafiltration of human skim milk, removing cream from pooled human milk, and pooling the milk of multiple donors. Because the base claim describes a process, it is unclear whether the additional steps described in dependent claim 67 are intended to refer to additional process steps required to infringe this claim, or whether they are intended to refer to product-by-process limitations that can be infringed without literally performing the recited process steps. Therefore it is unclear what is required to infringe this claim, rendering it indefinite.
Additionally, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 63 and 68 recite the broad recitation “at least 10g,” and the claim also recites “15g, 18g, 20g, or 25g,” which is the narrower statement of the range/limitation. Claims 65 and 70 additionally recite the broad range “at least 3 days,” and the narrow range “7 days, 9 days, or 14 days.” Claim 66 recites the broad range “at least 10,” and the narrow ranges “at least, at least 50, or at least 100.” Claim 67 recites the broad range “at least 50,” and the narrow ranges “100, or 150.” Claim 69 recites the broad range “at least 7,” and the narrow range “9 or 14.” Claims 72, 73, and 80 recite the broad range “at least 3 days,” and the narrow range “5 days, or 7 days.” Claim 78 recites the broad ranges “at least 7,” and “at least until 7,” and the narrow ranges “14, or 21,” and “14, 21, 28, 35.” Claim 79 refers to the broad range “antibiotics,” and the narrow range, “optionally wherein the antibiotic comprises one or more of,” a number of options. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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 61, 62, 65-70, 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 61 is directed to a process for maintaining engraftment of B. longum subsp infantis (B. infantis) in an adult subject comprising administering to the subject one or more synthetic human milk oligosaccharides. The claim further describes the subject as having previously been treated with B. infantis and a concentrated milk permeate. 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 claims 61 and 72 as presently pending describe 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.
Still further, as discussed under 35 USC 112(b) above, it is unclear whether the limitation “wherein the subject is an adult who has previously been administered,” appearing in these claims actually amounts to a limitation requiring that the subject being treated possess certain characteristics rather than requiring the performance of an initial process step of actually administering the recited compositions to the subject. Therefore according to the broadest reasonable interpretation this claim limitation is met if the subject to whom the HMO is administered is an adult who displays engraftment of B. longum subsp infantis, regardless of whether said engraftment was the result of a process involving administering a specific human milk permeate composition.
Regarding claim 62, p. 4 paragraph 10 of Kyle describes the MMO as comprising thirteen different oligosaccharides and mentions oligosaccharides recited in present claim 62. Regarding claims 65-70, 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.
For these reason Kyle et al. anticipates the present claims.
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)
The disclosure of Kyle et al. is discussed above. While as discussed under 35 USC 102 above, Kyle et al. is considered to anticipate the broadest reasonable interpretation of the claimed invention, even assuming for the sake of argument that the claims are interpreted as to claim a process comprising two separate steps, the first being administering a synbiotic comprising B. infantis and human milk permeate and the second comprising administering a synthetic HMO which is not human milk permeate, the claimed invention would still have been obvious over the prior art.
In particular, as discussed previously Kyle describes using MMO isolated from natural sources. Additionally, Kyle discloses a process for obtaining HMO by defatting human milk to obtain skim milk, ultrafiltering the skim milk, and obtaining a permeate comprising lactose and human milk oligosaccharides. (p. 15 paragraphs 50-51)
It would have been obvious to one of ordinary skill in the art at the time of the invention to perform the initial B. infantis administration step using a human milk permeate such as that described in example 1 of Kyle. It would furthermore have been obvious to perform the later steps of administering the HMO in the absence of a probiotic using HMO produced synthetically. Specifically, Kyle et al. describes both synthetic production and isolation form human milk as viable sources for obtaining HMOs for use in the disclosed treatment. Therefore one of ordinary skill in the art would have considered them to be equivalents usable for the same purpose and would have found it to be obvious to substitute one for the other absent a finding of criticality.
Regarding claims 63-66 and 68-71, Kyle et al. does not specifically describe the claimed doses, frequency, or length of administration. 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 claim 66, Thurl et al. (Reference included with PTO-892) 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.
Claim 67 is 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 John et al. (Reference included with PTO-892)
The disclosure of Kyle et al. is discussed above. Kyle et al. does not specifically disclose a method wherein the milk is pooled from multiple donors. However, John et al. discloses that donated human milk is pooled in milk banks. (p. 3 first – third paragraphs, p. 5 second paragraph) Including milk form more donors in a pool reduced nutrient variability. (pp. 7-8, “results”) It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to produce the human milk permeate from pooling of donor milk from multiple samples. One of ordinary skill in the art would have considered this to be obvious based on the suggestion that such pooling reduced variability in the quality of the milk. Furthermore regarding the number of donors used in the pool, one of ordinary skill in the art would have seen John et al. as suggesting that the number of donors is a result-effective variable and would have found it to be obvious to increase the number of donors in the pool in order to reduce variability.
Therefore the invention taken as a whole is prima facie obvious.
Claims 77-80 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 included with PTO-892)
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 78-80, 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.
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 61, 62, 65-72, and 74-76 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 88 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 88 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 92 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 95 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 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 88 of ‘043 over an extended period (i.e. two or more times” would infringe a method of administering it to a patient who had already received the B longum subsp infantis synbiotic. 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.
Still further, as discussed under 35 USC 112(b) above, it is unclear whether the limitation “wherein the subject is an adult who has previously been administered,” appearing in these claims actually amounts to a limitation requiring that the subject being treated possess certain characteristics rather than requiring the performance of an initial process step of actually administering the recited compositions to the subject. Therefore according to the broadest reasonable interpretation this claim limitation is met if the subject to whom the HMO is administered is an adult who displays engraftment of B. longum subsp infantis, regardless of whether said engraftment was the result of a process involving administering a specific human milk permeate composition as recited in present claims 62-71.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 61, 62, 65-72, 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 88 of ‘043 over an extended period (i.e. two or more times” would infringe a method of administering it to a patient who had already received the B longum subsp infantis synbiotic. 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.
Still further, as discussed under 35 USC 112(b) above, it is unclear whether the limitation “wherein the subject is an adult who has previously been administered,” appearing in these claims actually amounts to a limitation requiring that the subject being treated possess certain characteristics rather than requiring the performance of an initial process step of actually administering the recited compositions to the subject. Therefore according to the broadest reasonable interpretation this claim limitation is met if the subject to whom the HMO is administered is an adult who displays engraftment of B. longum subsp infantis, regardless of whether said engraftment was the result of a process involving administering a specific human milk permeate composition as recited in present claims 62-71.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 61, 62, and 65-71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12364721. (Cited in PTO-892, herein referred to as ‘721) Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘721 render the present claims obvious.
Specifically, claim 1 of ‘721 claims a method for treating a subject comprising administering to the patient a mixture of prebiotic oligosaccharides falling within those recited in present claim 62 and a probiotic microorganism which is B. longum subsp infantis. Dependent claim 11 describes the subject as an adult human.
While the claims of ‘721 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 88 of ‘043 over an extended period (i.e. two or more times” would infringe a method of administering it to a patient who had already received the B longum subsp infantis synbiotic. 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 ‘721. 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 112(b) above, it is unclear whether the limitation “wherein the subject is an adult who has previously been administered,” appearing in these claims actually amounts to a limitation requiring that the subject being treated possess certain characteristics rather than requiring the performance of an initial process step of actually administering the recited compositions to the subject. Therefore according to the broadest reasonable interpretation this claim limitation is met if the subject to whom the HMO is administered is an adult who displays engraftment of B. longum subsp infantis, regardless of whether said engraftment was the result of a process involving administering a specific human milk permeate composition as recited in present claims 62-71.
.
Conclusion
No claims are allowed in this action.
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/ERIC OLSON/ Primary Examiner, Art Unit 1693 11/18/2025