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
Response to Amendment
Applicants’ submission of the replacement drawings filed 2 January 2026 is acknowledged. Applicants’ amendments of the specification and claims filed 2 January 2026 have been entered. Applicants’ remarks filed 2 January 2026 are acknowledged.
Claims 8-18 are cancelled. Claim 32 has been added. Claims 1-7 and 19-32 are pending and under examination to the extent they read on the elected species: A-a) wherein the autoimmune or inflammatory disease is inflammatory bowel disease; and B-a) wherein the inflammatory bowel disease is Crohn’s disease.
Drawings
The objection to the drawings (Figures 2A-2B, 3A-3B, 4 and 5) under 37 CFR 1.83(a), because they fail to show details as described in the specification, is withdrawn in response to Applicants’ submission of the replacement drawings.
Specification
The objection to the specification for not including the updated status of the related applications is withdrawn in response to Applicants’ amendment of the specification.
Claim Rejections Withdrawn
The rejection of claims 19-26 under 35 U.S.C. 112(b), as being indefinite for using the phrase "such as", is withdrawn in response to Applicants’ amendment of the claims.
The rejection of claims 1-7 under 35 U.S.C. 112(a), as failing to comply with the enablement requirement, is withdrawn in response to Applicants’ amendment of independent claims 1 and 6 to limit “treating an autoimmune or inflammatory disease that comprises TNFa-mediated inflammation, IL-23-mediated inflammation, or both TNFa-mediated inflammation and IL-23 mediated inflammation”.
New Grounds of Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 his invention.
Claims 1-7 and 32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The specification as originally filed does not provide support for the invention as now claimed: “A method of treating an autoimmune or inflammatory disease that comprises TNFa-mediated inflammation, IL-23-mediated inflammation, or both TNFa-mediated inflammation and IL-23 mediated inflammation”. Applicants assert that no new matter has been added to the amendment of the claims filed 2 January 2026, and points to Examples 6-8 of the specification for support. However, while the specification discloses using the multispecific ISVD construct as claimed to treat an autoimmune or inflammatory disease that comprises inflammation mediated by IL-23, or inflammation mediated by both TNFa and IL-23, the instant specification as filed does not have support for treating an autoimmune or inflammatory disease that comprises “TNFa-mediated inflammation”. In Example 6, the specification shows multispecific ISVD construct inhibition of TNFa-induced NFkB activation in vitro, and there is no support for treating an autoimmune or inflammatory disease that comprises “TNFa-mediated inflammation”. In Examples 7-8, the specification shows the inhibitory effects of the multispecific ISVD construct on IL-23-induced mIL-22 production ex vivo and on IL-23-induced SIE promoter activation in vitro, and there is no support for treating an autoimmune or inflammatory disease that comprises “TNFa-mediated inflammation”. Since the instant claims recite limitations which were not clearly disclosed in the specification as filed, such limitations introduce new concepts and do not comply with the written description requirement set forth under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Applicants are required to cancel the new matter in the response to this Office Action. Alternatively, Applicants are invited to provide sufficient written support for the “limitations” indicated above. See MPEP 714.02 and 2163.06.
New claim 32 is further rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain 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.
Claim 32 recites a polypeptide that specifically binds TNFa and the p19 subunit of IL-23, wherein the polypeptide comprises at least three immunoglobulin single variable domains (ISVDs), wherein each of said ISVDs comprises three complementarity determining regions (CDR1 to CDR3, respectively), and each of the CDRs is defined as encompassing an amino acid sequence with 2 or 1 amino acid difference(s). For example, “a first ISVD comprises i) a CDR1 that is the amino acid sequence of SEQ ID NO: 6 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 6; ii) a CDR2 that is the amino acid sequence of SEQ ID NO: 10 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 10; and iii) a CDR3 that is the amino acid sequence of SEQ ID NO: 14 or an amino acid sequence with 2 or 1 amino acid difference(s) with SEQ ID NO: 14”. The specification, however, does not provide adequate written description for the variant polypeptides. It is well established in the art that the conformation of the CDRs influences binding to its target epitope (see Knappik et al., J. Mol. Biol., 2000, Vol. 296(1):57-86). The art teaches that even minor changes in sequence can result in major changes in function, especially if the minor sequence change occurs within an active site or alters the overall conformation of the molecule. For example, Rudikoff et al. (Proc. Natl. Acad. Sci, USA, 1982, Vol. 79:1979-1983) teaches that alteration of a single amino acid in the CDR of an antibody resulted in the loss of antigen-binding function. Further, Rabia et al. (Biochem. Eng. J., 2018, Vol. 137:365-374) teaches that it is extremely challenging to define the sequence determinants of antibody specificity; most mutations that increase affinity – such as those that simply increase hydrophobicity or charge – also reduce specificity. Without further testing, the skilled artisan cannot envision the detailed structures of the encompassed variant polypeptides that specifically bind to TNFa and the p19 subunit of IL-23, let alone those useful for treating an autoimmune or inflammatory disease in a subject.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making of the claimed product, or any combination thereof. In this case, there is no sufficient teaching regarding the correlation of structure and function. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed structures of the encompassed variant polypeptides, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that is part of the invention and reference to a method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, the specification only describes a polypeptide that specifically binds TNFa and the p19 subunit of IL-23, wherein the polypeptide comprises at least three immunoglobulin single variable domains (ISVDs), wherein each of said ISVDs comprises three complementarity determining regions (CDR1 to CDR3, respectively), optionally linked via one or more peptidic linkers; and wherein: a) a first ISVD comprises CDR1 to CDR3 set forth in the amino acid sequences of SEQ ID NOs: 6, 10 and 14, respectively; b) a second ISVD comprises CDR1 to CDR3 set forth in the amino acid sequences of SEQ ID NOs: 7, 11 and 15, respectively; and c) a third ISVD comprises CDR1 to CDR3 set forth in the amino acid sequences of SEQ ID NOs: 9, 13 and 17, respectively. There is no adequate written description for the full scope of the claimed molecules in the disclosure.
Allowable Subject Matter
Claims 19-31 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
CLAIMS 19-31 ARE OBJECTED.
CLAIMS 1-7 AND 32 ARE REJECTED.
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 Xiaozhen Xie, whose telephone number is 571-272-5569. The examiner can normally be reached on M-F, 8:30-5.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa L. Ford, can be reached on 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/XIAOZHEN XIE/Primary Examiner, Art Unit 1674
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