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 2-127 and 131-137 are canceled. Claim 138 is new. Claims 1, 128-130 and 138 are pending and under consideration in this action.
The instant claims are entitled to an effective filing date of 01/05/2018.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 130, and 138 are rejected under 35 U.S.C. 103 as being obvious over Hsiao (US2016/0120920) in view of Sharon (US 2021/0317508 filed Aug. 1, 2017) and Anselmo (US2017/0165201).
Regarding claim 1, Hsiao teaches treating MIA mice offspring with B. thetaiotaomicron, and then assaying for autism spectrum disorder (ASD)-related gastrointestinal and behavioral symptoms. The treatment with B. thetaiotaomicron corrects deficits in intestinal barrier integrity. See [0032]. Hsiao teaches physiologically acceptable carriers that may comprise amino acids, and polyethylene glycol (PEG). See [0025]. Hsiao teaches probiotics that may be available in, for example, capsules. See [0027].
Hsiao does not teach Parabacteroides merdae.
Sharon discloses that Parabacteroides merdae and an sOTU closely related to Bacteroides thetaiotaomicron are prevalent in all TD samples and absent from autism spectrum disorder samples. See [0210]. TD samples are fecal samples from human typically developing. See [0202]. Sharon teaches a composition, device, method or kit comprising, consisting essentially of, or consisting of at least 2 of any of the bacteria listed in tables 1A and/or 1B. See [0053]. Table 1B includes Parabacteroides and Bacteriodetes. See [0047] for table 1B.1. Furthermore, Sharon teaches composition or kit comprising binding agents. See [0053]. The binding target is an antigen comprising, consisting essentially of, or consisting of a metabolite for example lysine (i.e. a 5AV precursor). See [0061].
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to combine Sharon’s Parabacteroides merdae with Hsaio’s B. thetaiotaomicron. One of ordinary skill in the art would have been motivated to do so because Sharon discloses that P. merdae and B. thetaiotaomicron are absent in autism spectrum disorder samples. There would have been a reasonable expectation of success because Hsiao discloses Bacteroides thetaiotaomicron compositions for autism spectrum disorder; and Sharon teaches compositions that can comprise or consist essentially of Parabacteroides and Bacteriodetes (which is the phylum that includes the genus Bacteroides).
Hsiao and Sharon do not teach a taurine precursor and/or a 5-Aminovaleric acid precursor. However, Sharon suggests compositions comprising lysine, which is a 5-AV precursor.
Hsiao and Sharon do not teach a composition that is encapsulated in a pH-sensitive coating.
Anselmo teaches a formulation of mucoadhesive polymeric encapsulated microorganisms or antigenic components thereof. See claim 1 of Anselmo. The one or more mucoadhesive polymers comprise an outer layer of pH-responsive polymers. See claim 2 of Anselmo. Some pH-responsive polymers include poly(L-lysine) (i.e. the 5AV precursor lysine). See [0132]. The one or more mucoadhesive polymers are applied sequentially layer-by-layer onto the microorganism (i.e. a coating). See claim 4 of Anselmo. Anselmo teaches lubricants and binders including polyethylene glycol (PEG). See [0173]. Furthermore, Anselmo suggests that PEGylation is a preferred chemical modification for pharmaceutical usage. See [0191]. Anselmo further teaches pH-responsive (i.e. pH-sensitive) polymers that are polymethacrylate polymers. See claim 7 of Anselmo.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to combine Sharon’s P. merdae and Hsaio’s B. thetaiotaomicron with Hsaio’s PEG carrier in view of Anselmo, and to further add the poly(L-lysine), and pH-responsive polymethacrylate polymer of Anselmo. One of ordinary skill in the art would have been motivated to select PEG from the list of carriers taught by Hsiao because Anselmo suggests that PEG can act as a lubricant, a binder, and it can be used for PEGylation in pharmaceuticals. There would have been a reasonable expectation of success because Hsiao teaches PEG amongst a finite list of three surfactant carriers, and Hsiao further suggests using lubricants and binders ([0025] of Hsiao). One of ordinary skill in the art would have been further motivated to add the poly(L-lysine) of Anselmo because Anselmo suggests that protein-based probiotic encapsulates may enhance survival of probiotics ([0004] of Anselmo). There would have been a reasonable expectation of success because in paragraph [0132] Anselmo teaches the poly(L-lysine) amongst a finite list of other pH-responsive polymers to choose from. One of ordinary skill in the art would have been further motivated to add an additional pH-responsive polymer including the polymethacrylate polymer of Anselmo because Anselmo explicitly teaches formulations in which the pH-responsive polymers are polymethacrylate polymers (claim 7 of Anselmo). There would be a reasonable expectation of success because Anselmo teaches sequentially layering polymers onto a microorganism (claim 3 of Anselmo).
Regarding claim 130, Anselmo teaches pH-responsive polymers including poly(L-lysine) (i.e. a 5AV precursor). See [0132].
Regarding claim 138, Hsiao teaches that B. thetaiotaomicron improves anxiety-like repetitive and communication behavior in MIA mice. See [0032]. Hsiao teaches improving an anxiety behavior. See [0037] and [0046]. Hsiao teaches improving anxiety and/or repetitive behavior. See [0050] and [0052].
Claims 128 and 129 are rejected under 35 U.S.C. 103 as being obvious over Hsiao (US2016/0120920), Sharon (US 2021/0317508 filed Aug. 1, 2017) and Anselmo (US2017/0165201), as applied to claims 1, 130 and 138 above, and further in view of Kern (J Am Nutraceut Assoc, 2008, 11, 36-41), with evidence from Matsuda (Nutrients. 2024 May 25;16(11):1622).
Regarding claim 128, Hsiao teaches physiologically acceptable carriers that may comprise amino acids, and polyethylene glycol (PEG). See [0025].
Anselmo teaches using whey proteins to encapsulate microorganism. See [0096] and [0083].
Hsiao, Sharon and Anselmo do not teach a composition that consists of the taurine precursor and the 5AV precursor.
Kern teaches supplementing children with autism or autism spectrum disorder with non-denatured whey protein isolate (NWPI) (i.e. a taurine precursor). See the abstract. Kern suggests that glutathione (GSH) is lower in children with autism. Cysteine is the rate-limiting substrate for GSH production. See the first and third paragraphs of the introduction. NWPI is cysteine rich. See the second paragraph on page 37. Kern suggests that children with autism do not have problems tolerating cysteine in this form. See the left column on page 39.
Evidentiary reference Matsuda states that whey protein intake may elevate taurine. See the second paragraph of section 4.2 on page 9.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to add the NWPI of Kern to the composition of Hsiao, Sharon and Anselmo discussed above. One of ordinary skill in the art would have been motivated to do so because Kern suggests that children with autism tolerate cysteine in this form. There would have been a reasonable expectation of success because Anselmo suggests that whey protein can be added encapsulate microorganisms, and Kern demonstrates administering the NWPI to children with autism.
Regarding claim 129, Kern teaches that NWPI is cysteine rich. See the second paragraph on page 37.
Response to Arguments
Applicant's arguments, filed 07/01/2026, have been fully considered but they do not apply to the new grounds of rejection set forth above.
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 1, 119-123, and 128-135 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,224,624 B2 to Needham, hereinafter Needham ‘624 (priority to Feb. 14, 2017), in view of Sharon (US 2021/0317508 filed Aug. 1, 2017), Anselmo (US 2017/0165201), and Kern (J Am Nutraceut Assoc, 2008, 11, 36-41), with evidence from Matsuda (Nutrients. 2024 May 25;16(11):1622).
Claim 1 of Needham ‘624 recites a composition or product combination comprising a genetically engineered Bacteroides ovatus comprising a loss-of-function mutation in a gene encoding BO1194, and a genetically engineered Lactobacillus plantarum comprising a loss-of function mutation in a gene encoding phenolic acid decarboxylase (PAD).
Claim 4 of Needham ‘624 recites a method of reducing or inhibiting production of 4-ethylphenol (4EP) and/or 4-ethylphenyl sulfate (4EPS) in a subject in need thereof, the method comprising:
a) administering to the subject a therapeutically effective amount of a composition or product combination comprising a genetically engineered Bacteroides ovatus comprising a lose-of-function mutation in a gene encoding BO 1194, and a genetically engineered Lactobacillus plantarum comprising a loss-of-function mutation in a gene encoding phenolic acid decarboxylase (PAD); and
b) permitting the genetically engineered Bacteroides ovatus and the genetically engineered Lactobacillus plantarum to proliferate in a gastrointestinal tract of the subject, whereby production of 4EP and/or 4EPS in the subject is reduced or inhibited.
Claim 5 of Needham ‘624 recites the method of claim 4, wherein reducing the levels of 4EP and/or 4EPS ameliorates, delays the onset of, or decreases the likelihood of a symptom associated with anxiety and/or autism spectrum disorder (ASD) in the subject.
Claim 18 of Needham ‘624 recites the composition or product combination of claim 1, further comprising Bacteroides fragilis or Bacteroides thetaiotaomicron.
Claim 19 of Needham ‘624 recites the composition or product combination of claim 1, wherein the probiotic composition or product combination is present in a food product.
Claim 20 of Needham ‘624 recites the composition or product combination of claim 1, further comprising a pharmaceutically acceptable carrier or excipient.
The patent claims of Needham ‘624 lack: a composition consisting of: a) Parabacteroides merdae and one or more types of isolated bacteria selected from Bacteroides ovatus, and Bacteroides thetaiotaomicron; b) a taurine precursor and/or a 5AV precursor; c) PEG and d) wherein the composition is encapsulated in a pH-sensitive coating (relevant to instant claim 1); wherein b) consists of the taurine and 5AV precursors (relevant to instant claim 128); a taurine precursor that is cysteine , cysteine sulfinic acid, homocysteine, cystathionine, hypotaurine or a mixture thereof (relevant to instant claim 129); a 5AV precursor that is lysine, cadaverine, 1-piperdeine or a mixture thereof (relevant to instant claim 130); and one or more symptoms associated with ASD that comprises a sociability disorder, anxiety, and/or a repetitive behavior (relevant to instant claim 138).
However, Sharon discloses that Parabacteroides merdae and an sOTU closely related to Bacteroides thetaiotaomicron are prevalent in all TD samples and absent from autism spectrum disorder samples. See [0210]. Sharon teaches a composition, device, method or kit comprising, consisting essentially of, or consisting of at least 2 of any of the bacteria listed in tables 1A and/or 1B. See [0053]. Table 1B includes Parabacteroides and Bacteriodetes. See [0047] for table 1B.1. Anselmo teaches a formulation of mucoadhesive polymeric encapsulated microorganisms, wherein the one or more mucoadhesive polymers comprise an outer layer of pH-responsive polymers. See claims 1-2 of Anselmo. Anselmo teaches pH-responsive polymers including poly(L-lysine) (i.e. the 5AV precursor lysine) and polymethacrylate polymers. See [0132] and claim 7 of Anselmo. Anselmo teaches lubricants and binders including polyethylene glycol (PEG). See [0173]. Furthermore, Anselmo suggests that PEGylation is a preferred chemical modification for pharmaceutical usage. See [0191]. Kern teaches supplementing children with autism or autism spectrum disorder with non-denatured whey protein isolate (NWPI), which is cysteine rich. See the abstract and the second paragraph on page 37. Evidentiary reference Matsuda states that whey protein intake may elevate taurine. See the second paragraph of section 4.2 on page 9.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to combine only the B. ovatus and/or B. thetaiotaomicron of Needham ‘624 with the P. merdae of Sharon, and Anselmo’s PEG, poly(L-lysine) and pH-responsive polymethacrylate polymer, and to further add the NDWPI of Kern in order to reduce one or more symptoms or conditions associated with autism spectrum disorder.
Response to Arguments
Applicant's arguments, filed 07/01/2026, have been fully considered but they do not apply to the new grounds of rejection set forth above.
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 KIMBERLY C BREEN whose telephone number is (571)272-0980. The examiner can normally be reached M-Th 7:30-4:30, F 8:30-1:30 (EDT/EST).
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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
/K.C.B./Examiner, Art Unit 1657
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