CTNF 18/014,863 CTNF 87116 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 Responsive to communication entered 10/15/2025. Priority This application, Pub. No. US 2023/0287142 A1, published 09/14/2023, is a § 371 National Stage of International Patent Application No. PCT/US2021/040424, filed 07/06/2023, Pub. No. WO 2022/010830, and claims priority to US provisional application No. 63/048,352, filed 07/06/2020. 12-151 AIA 26-51 12-51 Status of Claims Claims 1-15, 21-24 and 27 are currently pending. Claims 1-31 have been originally filed. Claims 16-20, 25-26 and 28-31 have been cancelled, as set forth in Applicant’s Preliminary amendment filed 07/25/2023. Claims 1-15, 21-24 and 27 have been subject to election/restriction requirement mailed 08/15/2025. Claims 21-24 and 27 are withdrawn from consideration. Claims 1-15 are examined. Election/Restrictions Applicant’s election of Group I, Claims 1-15, drawn to a polypeptide, and the species: an antibody comprising the amino acid sequence of SEQ ID NO: 80, wherein: VH CDR1 has the sequence SEQ ID NO: 2, VH CDR2 has the sequence SEQ ID NO: 4, VH CDR3 has the sequence SEQ ID NO: 5, VL CDR1 has the sequence SEQ ID NO: 6, VL CDR2 has the sequence SEQ ID NO: 22, and VL CDR3 has the sequence SEQ ID NO: 25, as the species of the polypeptide; Horseradish Peroxidase (HRP) as a detectable label; 08-25-02 Loratadine as a therapeutic agent, in the reply filed on 10/15/2025 is acknowledged and entered. Because Applicant did not distinctly and specifically point out the supposed errors in the election/restiction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Applicant identified Claims 1-15 as readable on the elected species. 08-06 Claims 21-24 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to the nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/15/2025. Information Disclosure Statement The information disclosure statement, submitted on 01/06/2023, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the Examiner. Specification The use of the terms FAM™, TAMRA™, ROX™, JOE™, HEX™, BODIPY®, Texas Red®, Cy7®, Cy5®, Cy5.5® , Alavert®, Claritin®, etc., which are a trade name or a mark used in commerce, have been noted in this application. See, for example, paragraphs [00135] and [00144] of the specification filed 01/06/2023. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. PNG media_image1.png 174 914 media_image1.png Greyscale PNG media_image2.png 170 918 media_image2.png Greyscale PNG media_image3.png 170 968 media_image3.png Greyscale PNG media_image4.png 140 972 media_image4.png Greyscale Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required. 06-31 AIA The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification. Claim Rejection - 35 USC § 112 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 112 that form the basis for the rejections under this section made in this Office action: 07-30-01 AIA 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 his invention. 07-30-02 AIA 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. 07-31-01 Claims 1-15 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 (“genus-species”). The claims, as recited in independent Claim 1, are drawn to: PNG media_image5.png 640 1066 media_image5.png Greyscale PNG media_image6.png 504 1062 media_image6.png Greyscale PNG media_image7.png 452 1070 media_image7.png Greyscale MPEP § 2163(II)(A)(3)(a)(ii) states that the written description requirement for a claimed genus may be satisfied through description of: – A representative number of species by actual reduction to practice, reduction to drawings, or – Disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, – By functional characteristics coupled with a known or disclosed correlation between function and structure. It is the Examiner’s position that Claims 1-15 do not meet the written description provision of 35 U.S.C. §112(a). The Examiner’s position is based on the following facts and considerations. First, although the instant invention is entitled “HISTAMINE BINDING POLYPEPTIDES AND USES THEREOF,” the claims are broadly drawn to polypeptides, which function is not identified. Applicant is reminded that, according to MPEP 2107.01, IV. RELATIONSHIP BETWEEN 35 U.S.C. 112(a) or PRE-AIA 35 U.S.C. 112, FIRST PARAGRAPH, AND 35 U.S.C. 101, compliance with § 112 requires a description of how to use presently useful inventions. Second, the claims cover an enormous genus of polypeptides due to multiple combinations of the recited CDRs and their at least 85% identical analogs. Third, the instant disclosure is limited to preparation of a single chain variable fragment (ScFv) of SEQ ID NO: 82, wherein the VH and VL domains are linked by a peptide linker comprising the amino acid sequence EGKSSGSGSESKAS (SEQ ID NO: 26), which ScFv has VL CDRs of SEQ ID NOs: 20, 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively, and its 19 mutated variants (mutations are indicated in bold and underlined) having the following specific combinations of VH and VL CDRs set forth in Tables 1 and 2 of the specification as follows: (1) VL CDRs SEQ ID NOs: 20, 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (2) VL CDRs SEQ ID NOs: 19 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (3) VL CDRs SEQ ID NOs: 20, 21 , 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (4) VL CDRs SEQ ID NOs: 20, 22, 24 , respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (5) VL CDRs SEQ ID NOs: 20, 22, 25, respectively, and VH CDRs SEQ ID NOs: 1 , 4, 5, respectively; (6) VL CDRs SEQ ID NOs: 20, 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 3 , 5, respectively; (7) VL CDRs SEQ ID NOs: 20, 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 83 , respectively; (8) VL CDRs SEQ ID NOs: 6 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (9) VL CDRs SEQ ID NOs: 7 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (10) VL CDRs SEQ ID NOs: 8 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (11) VL CDRs SEQ ID NOs: 9 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (12) VL CDRs SEQ ID NOs: 10 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (13) VL CDRs SEQ ID NOs: 11 , 22, 23 , respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (14) VL CDRs SEQ ID NOs: 12 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (15) VL CDRs SEQ ID NOs: 13 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (16) VL CDRs SEQ ID NOs: 14 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (17) VL CDRs SEQ ID NOs: 15 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; (18) VL CDRs SEQ ID NOs: 16 , 22, 25, respectively, and VH CDRs SEQ ID NOs:2, 4, 5, respectively; (19) VL CDRs SEQ ID NOs: 17 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively; and (20) VL CDRs SEQ ID NOs: 18 , 22, 25, respectively, and VH CDRs SEQ ID NOs: 2, 4, 5, respectively. Fourth, the art is highly unpredictable with regard to antibodies, at least because correlation between structure and function is less likely for antibodies than for other molecules. As illustration of the unpredictability in the art, CN 110028579 A , published 07/19/2019, teaches an anti-Nipah virus G protein monoclonal antibody comprising VL CDRs, which are identical to the instantly claimed VL CDR1 of SEQ ID NO: 6, VL CDR2 of SEQ ID NO: 22, and VL CDR3 of SEQ ID NO: 25: PNG media_image8.png 334 936 media_image8.png Greyscale Further evidence of lack of correlation between function and structure for the instantly claimed genus of polypeptides is Applicant’s own data set forth in Table 1 of the specification showing that not all of the claimed polypeptides can be useful for histamine detection: PNG media_image9.png 460 854 media_image9.png Greyscale Therefore, it is deemed that the specification fails to provide adequate written description for the scope of Claims 1-15 and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. 07-34-01 AIA Claim 5 is 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 pre-AIA the applicant regards as the invention. Recitation in Claim 5 “wherein the polypeptide is selected from the group consisting of comprise the group consisting of” renders unclear whether the claim is intended to be in Markush format. Regarding the elected species (2) , Horseradish Peroxidase (HRP) as a detectable label, Buckler et al ., US 5,112,738 A, published 05/12/1992, teach: PNG media_image10.png 194 620 media_image10.png Greyscale Col. 12; Emphasis added Regarding the elected species (3) , Loratadine as a therapeutic agent, the Examiner notes that one of skill in the art would have known about the use of antibody-drug conjugates: PNG media_image11.png 172 976 media_image11.png Greyscale PNG media_image12.png 172 974 media_image12.png Greyscale Accordingly, it would be obvious to make a conjugate of the instantly claimed polypeptide with a commercially available antihistamine drug loratadine. Conclusion No claims are allowed. Patentable Subject Matter Regarding the elected species (1) , no prior art was found for a histamine binding polypeptide comprising VH CDR1 of SEQ ID NO: 2, VH CDR2 of SEQ ID NO: 4, VH CDR3 of SEQ ID NO: 5, VL CDR1 of SEQ ID NO: 6, VL CDR2 of SEQ ID NO: 22, and VL CDR3 of SEQ ID NO: 25. Any inquiry concerning this communication or earlier communications from the examiner should be directed to GALINA M YAKOVLEVA whose telephone number is (571)270-3282. The examiner can normally be reached on M-F 8:30 AM-5:00 PM. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GREGORY S EMCH can be reached on (571)272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /GALINA M. YAKOVLEVA/Primary Examiner, Art Unit 1678 Application/Control Number: 18/014,863 Page 2 Art Unit: 1678