DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Applicants’ Amendment
1) Acknowledgment is made of Applicants’ amendment filed 06/23/25 in response to the non-final Office Action mailed 12/23/24.
Status of Claims
2) Claims 1, 10, 25 and 27 have been amended via the amendment filed 06/23/25.
New claim 123 has been added via the amendment filed 06/23/25.
The examination has been extended to the Citrobacter rodentium pathogen species.
Claims 1, 4-6, 10, 21, 25, 27 and 123 are pending and are under examination.
Substitute Specification
3) Acknowledgment is made of Applicants’ substitute specification filed 06/23/25.
Allowable Subject Matter Indicated
4) The allowable subject matter, the acceptable claim language and issuance of a potential Examiner's amendment were conveyed to Applicants’ representative Ms. Elizabeth S. Mulski. She indicated that Applicants opt for an Office Action at this time. See attached Interview Summary.
Prior Citation of Title 35 Sections
5) The text of those sections of Title 35 U.S. Code not included in this action can be found in a prior Office Action.
Prior Citation of References
6) The references cited or used as prior art in support of one or more rejections in the instant Office Action and not included on an attached form PTO-892 or form PTO-1449 have been previously cited and made of record.
Objection(s) Withdrawn
7) The objections to the specification set forth in paragraphs 7(a), 7(b) and 7(c) of the Office Action mailed 12/23/24 are withdrawn in light of Applicants’ amendments.
8) The objection to claims 1 and 10 set forth in paragraph 17 of the Office Action mailed 12/23/24 is withdrawn in light of Applicants’ claim amendment.
Objection(s) to Claim(s) & Specification
9) 37 C.F.R 1.75(d)(1) provides, in part, that ‘the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description.’ Furthermore, 35 U.S.C § 132 states that no amendment shall introduce new matter into the disclosure of the invention.
Claim 1, as amended, includes the limitations: “inducing an immune response against a pathogen” ......... Citrobacter rodentium along with the deletion of the previous limitations “for the purpose of inducing an antigen-specific immune response against a pathogen”. The method as claimed requires induction of a general immune response, i.e., humoral and/or cellular, against the recited pathogen, for example, Citrobacter rodentium of no particular antigen-immunospecificity, i.e., irrespective of whether or not the pathogen is ica/pga PNAG-positive or non-ica/pga PNAG-positive, upon administration to a generic subject an effective amount of an isolated polysaccharide having the formula with the recited n, the recited R being -NH-CO-CH3 or -NH2 provided that less than 50% of the R are -NH-CO-CH3, wherein the isolated polysaccharide is conjugated to a carrier which is not required to be a protein carrier. However, there is no antecedent basis and descriptive support for the polysaccharide of the recited formula that is conjugated to any generic carrier including a non-protein carrier, which upon administration, by any route, induced an immune response against C. rodentium in a human or non-human subject. Applicants do not point to specific parts of the as-filed specification in support of the claim amendments. The as-filed specification lacks antecedent basis and descriptive support for the above-identified added limitations and for the current scope of the claim(s).
Rejection(s) Withdrawn
10) The provisional rejection of claims 1, 4-6, 10, 25 and 27 set forth in paragraph 9 of the Office Action mailed 12/23/24 on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 2, 5, 7, 8, 13, 16, 22, 23 and 25-27 of the U.S. application 17427763 is withdrawn in light of its issued status and Applicants’ claim amendments. This application has been issued as US patent 12397014.
11) The rejection of claims 1, 4-6, 10, 25 and 27 set forth in paragraph 10 of the Office Action mailed 06/23/25 on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1-3, 5, 7 and 30-37 of US patent 9474806 B2 (of record) is withdrawn in light of Applicants’ claim amendments.
12) The rejection of claims 1, 4-6, 10, 25 and 27 set forth in paragraph 11 of the Office Action mailed 06/23/25 on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1-3, 5-7 and 8-17 of US patent 10034927 B2 (of record) is withdrawn in light of Applicants’ claim amendments.
13) The rejection of claim 1 set forth in paragraph 13(a) of the Office Action mailed 06/23/25 under 35 U.S.C § 112(b) or 35 U.S.C § 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in light of Applicants’ claim amendments.
14) The rejection of claim 5 set forth in paragraph 13(b) of the Office Action mailed 06/23/25 under 35 U.S.C § 112(b) or 35 U.S.C § 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in light of Applicants’ claim amendment.
15) The rejection of claims 25 and 27 set forth in paragraph 13(c) of the Office Action mailed 06/23/25 under 35 U.S.C § 112(b) or 35 U.S.C § 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in light of Applicants’ claim amendment.
16) The rejection of claims 4-6, 10, 25 and 27 set forth in paragraph 13(d) of the Office Action mailed 06/23/25 under 35 U.S.C § 112(b) or 35 U.S.C § 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in light of Applicants’ amendment to the base claim.
17) The rejection of claims 1, 4-6, 10, 21, 25 and 27 set forth in paragraph 15 of the Office Action mailed 06/23/25 under 35 U.S.C § 102(b) as being anticipated by Biemans et al. (US 8703148 B2, of record) (Biemans et al., ‘148) as evidenced by WO 2004/043405 A2 (of record) is withdrawn in light of Applicants’ claim amendments.
18) The rejection of claims 1, 4-6, 10, 21, 25 and 27 set forth in paragraph 16 of the Office Action mailed 06/23/25 under 35 U.S.C § 102(b) as being anticipated by Pier et al. (WO 2010/011284 A2, of record) (Pier et al., ‘284) is withdrawn in light of Applicants’ claim amendments.
Rejection(s) under 35 U.S.C § 112(a) or (Pre-AIA ) First Paragraph
19) The following is a quotation of 35 U.S.C § 112(a):
(a) IN GENERAL.- The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. § 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out the invention.
20) Claim 1 and the dependent claims 4-6, 10, 21, 27 and 123 are rejected under 35 U.S.C § 112(a) or 35 U.S.C § 112 (pre-AIA ), first paragraph, as containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claim 1, as amended, includes the limitations: “inducing an immune response against a pathogen” ......... Citrobacter rodentium ....” along with the deletion of the previous limitations “for the purpose of inducing an antigen-specific immune response against a pathogen”. The method as claimed requires induction of a general immune response, i.e., humoral and/or cellular, against the recited pathogen, Citrobacter rodentium, of no particular antigen-immunospecificity, i.e., irrespective of whether or not the pathogen is ica/pga PNAG-positive or non-ica/pga PNAG-positive, upon administration to a generic subject an effective amount of an isolated polysaccharide having the formula with the recited n, the recited R being -NH-CO-CH3 or -NH2 provided that less than 50% of the R are -NH-CO-CH3, wherein the isolated polysaccharide is conjugated to a carrier. The carrier to which said isolated polysaccharide is conjugated is not required to be a protein carrier, and therefore encompasses all non-protein carriers. However, there is no descriptive support for the polysaccharide of the recited formula that is conjugated to any generic carrier including a non-protein carrier, which upon administration, by any route, induced an immune response against C. rodentium. Applicants do not point to specific parts of the as-filed specification in support of the claim amendments. There is no descriptive support for the above-identified added limitations and for the claimed method of current scope. Therefore, the added limitations in the claims and the currently claimed scope of the claims and those dependent therefrom are considered to be new matter. See M.P.E.P 608.04 to 608.04(c).
Applicants are invited to point to the descriptive support in specific pages and lines of the disclosure, as originally filed, for the limitation identified above, or alternatively, remove the new matter from the claim(s). Applicants should specifically point out the support for any amendments made to the disclosure. See MPEP 714.02 and 2163.06.
21) Claim 1 and the dependent claims 4-6, 21, 27 and 123 are rejected under 35 U.S.C § 112(a) or 35 U.S.C § 112 (pre-AIA ), first paragraph, as containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The purpose of the written description requirement is ‘to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him.’ In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978). The analysis of whether the as-filed specification complies with the written description requirements calls for the Office to compare the scope of the claims with the scope of the description to determine whether Applicants have demonstrated possession of the full scope of the claimed invention at the time of the invention. In the instant application, an analysis of the scope of the claims indicates the following.
Independent claim 1 is representative of the claimed invention. Claim 1, as amended, is drawn to a method comprising administering to a generic subject an effective amount of an isolated polysaccharide having the formula with the recited n and the recited R being -NH-CO-CH3 or -NH2 provided that less than 50% of the R are -NH-CO-CH3, wherein the isolated polysaccharide is conjugated to a carrier, wherein the method is required to induce an immune response, humoral and/or cellular, to the recited Citrobacter rodentium, the pathogen species being examined currently. The carrier genus to which said isolated polysaccharide is conjugated is not required to be a protein carrier, but encompasses all non-protein carrier species. The as-filed specification states that the carrier can be a polysaccharide carrier (see last full paragraph of page 4) and therefore, a fully acetylated, partially de-acetylated, and a fully deacetylated N-acetyl beta 1-6 glucosamine polysaccharide or oligosaccharide species are encompassed within the scope of the recited carrier genus. The step of administering includes any route of administration including local administration as is claimed in the dependent claim 27. The immune response, i.e., humoral and/or cellular, induced to the pathogen Citrobacter rodentium is of no particular antigen-immunospecificity. Page 2 of the instant specification (WO 2013/181348) states that the Citrobacter rodentium pathogen lacks an identifiable genetic locus related to the ica locus of Staphylococci or a pga locus of E. coli, which encodes proteins involved in PNAG and related polysaccharide synthesis in certain bacteria. The pathogen is therefore referred to as non-ica/pga pathogen to indicate that it does not have identifiable ica or pga loci. The claimed method is required to induce an immune response to this non-ica/pga Citrobacter rodentium pathogen species. Citrobacter rodentium is recognized in the art as a host-adapted mouse pathogen and as a natural non-invasive bacterial pathogen which infects the distal colon of mice. See the 1st sentence of Abstract of MacDonald et al. Int. J. Med. Microbiol. 293: 87-93, 2003. The dependent claim 21 requires the subject to whom the polysaccharide-carrier conjugate is administered to be a human, and the administered polysaccharide-carrier conjugate in the method of the dependent claim 123 is required to induce an immune response in a subject having an infection caused by this mouse pathogen Citrobacter rodentium. However, at the time of the invention, Applicants were not in possession of the method as claimed, wherein the polysaccharide of the recited formula conjugated to any carrier, upon administration by any route including a local route to any subject, mouse or human having or not having an infection caused by Citrobacter rodentium, induced a humoral and/or cellular immune response against the Citrobacter rodentium mouse pathogen. At the time of the invention, Applicants were not in possession of the full scope of the method as claimed.
A review of the instant specification indicates that a showing of possession in the instant application is limited to the disclosure in Table 1, Example 2, and the sentence bridging pages 34 and 35. Table 1 documents a green positive result when the F598 monoclonal antibody was used with a strain of Citrobacter rodentium. The sentence bridging pages 34 and 35 of the as-filed specification states that PNAG was detected around microbes associated with the epithelial cells in the GI tract of a mouse experimentally infected with C. rodentium. Example 2 states that Mab F598 is a human IgG1 specific to PNAG and that when GI tract samples of an infected mouse was reacted with Mab F598, the presence of PNAG in Citrobacter rodentium colonies in the mouse GI tract was observed. However, these in vitro observations are insufficient to show possession, at the time of the invention, of the claimed in vivo method of administering to a subject including a human subject the isolated polysaccharide of the recited formula that is conjugated to any carrier, protein or non-protein carrier, wherein said conjugate induced an antibody and/or cell-mediated immune response in vivo in the subject to the Citrobacter rodentium, a pathogen identified in the specification as a non-ica/pga pathogen. These in vitro results observed with the use of the Mab F598 are not equivalent to the claimed method of inducing an immune response of no particular antigen-immunospecificity to the non-ica/pga C. rodentium pathogen upon administration to a mammalian or a non-mammalian subject having or not having a C. rodentium infection, the recited polysaccharide-carrier conjugate.
The written description inquiry is case and context-specific. It “depend[s] on the nature of the claimed invention and the knowledge of one skilled in the art at the time an invention is made and a patent application is filed.” Ariad, 560 at 1372. A number of factors guide the inquiry, including “the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, and the predictability of the aspect at issue.” Ariad, 560 at 1372 [Emphasis added]. According to MPEP 2163 [Emphasis added]:
The description needed to satisfy the requirements of (pre-AIA ) 35 U.S.C § 112 “varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084. Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art.
Evidence required to demonstrate possession of the invention is fact-specific and varies inversely with the maturity and predictability of the technology area. Inventions in “unpredictable” arts, as in the instant case, are subject to greater scrutiny under the written description requirement, and require a greater showing of possession than more predictable arts. In the instant application, the precise structure of the isolated polysaccharide having the formula with the recited n and the recited R being -NH-CO-CH3 or -NH2 provided that less than 50% of the R are -NH-CO-CH3, wherein the isolated polysaccharide is conjugated to structurally variable species of the huge carrier genus has not been correlated with the requisite function of induction of an immune response in a subject, mammalian or non-mammalian, to Citrobacter rodentium, a pathogen identified in the specification as a non-ica/pga pathogen. The results of in vitro reaction with Mab F598 and in vitro detection of Citrobacter rodentium in gastrointestinal samples of a mouse infected with Citrobacter rodentium are not relevant since the claimed method is not a method of detecting Citrobacter rodentium in the gastrointestinal samples of an infected mouse. These in vitro results are insufficient to meet the written description requirements. A mere plan or wish of inducing an immune response against the Citrobacter rodentium pathogen is insufficient to satisfy the provisions of 35 U.S.C § 112(a) or (pre-AIA ), first paragraph. To satisfy the written description provision of 35 U.S.C § 112 (pre-AIA ), first paragraph or 35 U.S.C § 112(a), a convincing structure-function relationship must exist between the structure of the administered polysaccharide-carrier genus conjugate and the required function of induction of an immune response against the mouse pathogen Citrobacter rodentium, which correlative evidence and a showing of possession at the time of the invention is lacking. Note that the written description provision of 35 U.S.C § 112 (pre-AIA ), first paragraph is severable from its enablement provision. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991) states “we hereby reaffirm, that 35 U.S.C § 112 (pre-AIA ), first paragraph, requires a ‘written description of the invention’ which is separate and distinct from the enablement requirement”. In re Ruschig, 379 F.2d 990 (CCPA 1967) states that written description is one of three distinct requirements under 35 U.S.C § 112 (pre-AIA ), first paragraph. MPEP § 2163.02 states: ‘an objective standard for determining compliance with the written description requirement is, does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed’. It must be noted that "[t]he applicant must ....... convey to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention." Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed.Cir.1991). The invention, is for purposes of the ‘written description’ inquiry, whatever is now claimed.” See page 1117. In sum, at the time of the invention, Applicants were not in possession of the method as claimed.
Conclusion
22) No claims are allowed.
23) Applicants’ claim 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 C.F.R 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 C.F.R 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.
Correspondence
24) Any inquiry concerning this communication or earlier communications from the Examiner should be directed to S. Devi, Ph.D., whose telephone number is (571) 272-0854. A message may be left on the Examiner’s voice mail system. The Examiner is on a flexible work schedule, however she can normally be reached Monday to Friday from 7.00 a.m. to 4.00 p.m. (EST). If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's Supervisor, Gary Nickol, can be reached at (571) 272-0835. The fax phone number for the organization where this application or proceeding is assigned (571) 273-8300.
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/S. DEVI/
S. Devi, Ph.D.Primary Examiner
Art Unit 1645
October, 2025