DETAILED ACTION 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. Claims 4-23 are pending in the application, per the amendment filed on 10 September 2023. No Requirement for Restriction/Election has been mailed. Priority Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S .C. 120, 121, 365(c), or 386(c) is acknowledged. This application is the national stage entry of PCT/CN2021/1211285 filed on 28 September 2021, which claims the benefit of the Chinese foreign patent Application No. CN202011054187.5 file on 29 September 2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Claims 4-23 have an earliest effective US filing date of 29 September 2020 . Information Disclosure Statement The information disclosure statements (IDSs) submitted on: 03/28/2023 ; 01/14/2025; 07/11/2025; 09/05/2025; 12/04/2025; and 03/03/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Specification The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Specifically page 11 of the disclosure states: “ available at http://www.gcg.com ” twice. 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 appl icant regards as his invention. Claims 10-11, 16, 18, 20 and 22 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. Claims 10-11, 16, 18 , and 20 are indefinite wherein they recite the phrase "such as". This phase renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claim 10 recites, “ a single chain antibody (such as scFv ), (Fab')2, a single domain antibody, such as VHH ” and it is unclear if the scope of the claim encompasses scFv and VHH. Claim 11 recites, “wherein the antibody is multispecific antibody, such as bispecific antibody ” and it is unclear if bispecific antibodies are part of the invention. Claim 16, recites, “other substances, such as labels” ; it is unclear if the scope of the claim includes labels. Claim 18 recites, “ one or more other therapeutic agents, such as chemotherapeutic agent s”. It is unclear if the scope of the claim is intended to encompass chemotherapeutics. Claims 7 and 20 are indefinite wherein they recite "preferably". This renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention or not. Claim 7 recites, “ an amino acid sequence having one or more (preferably no more than 20 or 10, more preferably no more than 5, 4, 3, 2, 1) amino acid changes (preferably amino acid substitution, more preferably amino acid conservative substitution), compared to the amino acid sequence of SEQ ID NO: 100 ” and it is unclear whether or not the claim is limiting the changes to one or more, or 10, or no more than 1, since the claim recites all of these. MPEP § 2173.05(c) states 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. Claim 7 is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language (i.e. “more preferably no more than …1” is (a) merely exemplary, and therefore not required, or (b) a required feature of the claim , which happens to also recite “one or more…” . Claim 20 is similarly indefinite wherein it recites, “ preferably the therapeutic mode comprise radiotherapy or surgery ”. It is unclear if this limitation is merely exemplary or required. Claims 12-15 are directed to a n isolated nucleic acid that encodes the light chain variable region or heavy chain variable region, or light chain or heavy chain of the antibody binding to CD3 or antigen-binding fragment . Claim 12 depends from claim 4 which comprises sequences that have undefined amino acid residues ( exs . SEQ ID NOS: 103-107). Given the variability of the genetic code, the scope of nucleic acid molecules encoding wild-cared amino acid residues is entirely indefinite. Claim 22 is indefinite wherein it recites, “ an amino acid sequence of anyone of SEQ ID NO: 50, and the amino acid sequence having the mutations selected from the following at 1, 2 or 3 positions of H31, H32, H33, H52, H52A, H52C, H53, H54, H95, H96, H97, H98, H99, H100, H100A, H100B, H100C (Kabat number) according to the Kabat numbering ” and “ an amino acid sequence of anyone of SEQ ID NO: 80, and the amino acid sequence having the mutations selected from the following at 1, 2 or 3 positions of L24, L28, L29, L30, L31, L53, L91, L92, L93, L94 (Kabat number) according to the Kabat numbering ” . Reciting “ Anyone o f” followed by a single identified sequence , renders the scope of the claim unclear. Further, for example, SEQ ID NO: 50 is a 125 amino acid sequence yet residue 31 is not Histidine, so it is unclear what “H31” of the claim refers to. Even if, en arguendo , this indicates residue 31, then the scope of residues “100A”, “100B” and “100C” , as claimed, are entirely unclear. For purposes of applying prior art the claim will be interpreted as reading upon a humanized anti-CD3 antibody comprising mutations within the VH or VL variable regions, but outside of the antigen-binding regions (CDRs). 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 5 and 7 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. In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claim 5 recites amino acid sequences having at least 90% identity to any of the claimed VH or VL sequences; Claim 7 recites an amino acid sequence having at least 85%, 90%, 91%, 92%,93%, 94%, 95%, 96%, 97%, 98% or 99% identity with the amino acid sequence s recited in the claim . The se claims do not require that the sequences having identity possess any particular conserved sequence, structure , or other distinguishing feature . T herefore , the claims are drawn to a genus of antibody chain molecules. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see MPEP 2163(II)(3)(a)( i )(A), reduction to drawings MPEP 2163(II)(3)(a) ( i )(B), or by 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, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus MPEP 2163(II)(3)(a) ( i )(C). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. In the instant case, the only factor present in the claim is a recitation of requisite percent identity and a required function of binding CD3 . However, the specification does not identif y any particular portion of a sequence that must be conserved for this activity. It is well established that even a single amino acid change within the heavy chain can significantly alter the antigen binding ( Rudikoff et al., Proc Natl Acad Sci U S A. 1982 Mar;79(6):1979–1983 ). Thus, without adequate description of those variants that have >85% or >90% identity, but which retain anti-CD3 function, then there is inadequate written description for the genus encompassed by these claims. Additionally, t he specification fails to provide a representative number of species within the recited genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristic s or representative number of species, the specification does not provide adequate written description of the claimed genus. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115). Claims 19-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling fo r treating a tumor in a subject comprising administering the antibody of instant claim 4 , does not reasonably provide enablement for preventing tumors . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The factors to be considered in determining whether a disclosure would require undue experimentation include: A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands , 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01. T he breadth of the claims : The broadest reasonable interpretation of the claimed method is that it provides prevention of cancer (tumor of the claims) comprising administering an effective amount of the anti-CD3 antibodies of the claims. A skilled artisan would not know how to use the method with a reasonable expectation of success based solely on what is disclosed in the specification. T he amount of direction and existence of working examples : The specification teaches the antibodies of the invention reduces tumor size in an art-accepted models of gastric cancer (pg. 59, Example 13) and pancreatic cancer (pg. 60, Example 14). The art at the time of filing demonstrates other anti-CD3 antibodies have been approved for the treatment of hematological cancers (see Table 1; Lloyd et al. Frontiers in Oncology, 15: 1548446, Feb 2025). There is no evidence , however, within the disclosure as filed or in the art before the effective filing date, that demonstrates prevention of cancer comprising anti-CD3 antibodies, with a reasonable expectation of success . Thus, w hat is enabled by the working examples is narrow in comparison to the breadth of the claims . The level of one of ordinary skill : A person who could administer prophylactic cancer treatment would have to have a high level of skill and would be on the order of an Oncologist. The quantity of experimentation needed : The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success . A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. In the decision of Genentech, Inc, v. Novo Nordisk, 42 USPQ 2d 1001, (CAFC 1997), the court held that: "[p] atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" and that "[t] ossing out the mere germ of an idea does not constitute enabling disclosure". The court further stated that "when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art", "[ i ]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement". The instant specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, and practice the method as claimed without first making a substantial inventive contribution. Nature of the invention : Given that the nature of the invention is in vivo prevention of cancer , a person having ordinary skill in the art would have to perform multiple further in vivo experiments, in animal models that are predictive of preventing different cancers , in order to demonstrate use of the method with a reasonable expectation of success. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine’ within the art, and constitutes undue further experimentation in order to use the method with a reasonable expectation of successfully preventing tumors . Therefore, Claims 19-20 are rejected under 35 U.S.C. 112, first paragraph, for failing to meet the enablement requirement. Claim Rejections - 35 USC § 102 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis ( i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. 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. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim s 4 , 6- 7, and 9 -2 2 are rejected under 35 U.S.C. 102 (a)(1), or in the alternative under 102(a)(2), as being anticipated by WO 2007042261 , Micromet AG, published on 19 April 2007, and being effectively filed on 11 October 2005 (hereafter the Micromet AG publication). Regarding Claim 4 , drawn to an anti-CD3 antibody comprising the sequences of the claim, the Micromet AG prior art teaches many antibodies that are encompassed by instant claim 4. Specifically, the publication teaches the identical antibody of part s (16) comprising HCDR1 as shown in SEQ ID NO: 103, HCDR2 as shown in SEQ ID NO: 104, and HCDR3 as shown in anyone of SEQ ID NO: 105; LCDR1 as shown in SEQ ID NO: 29, LCDR2 as shown in SEQ ID NO: 30 and LCDR3 as shown in SEQ ID NO: 31; part (19) comprising HCDR1 as shown in SEQ ID NO: 1, HCDR2 as shown in SEQ ID NO: 2, and HCDR3 as shown in SEQ ID NO: 105; LCDR1 as shown in SEQ ID NO: 29, LCDR2 as shown in SEQ ID NO: 30 and LCDR3 as shown in SEQ ID NO: 31; part (21) comprising HCDR1 as shown in SEQ ID NO: 103, HCDR2 as shown in SEQ ID NO: 2, and HCDR3 as shown in SEQ ID NO: 105; LCDR1 as shown in SEQ ID NO: 29, LCDR2 as shown in SEQ ID NO: 30 and LCDR3 as shown in SEQ ID NO: 31; and part (22) comprising HCDR1 as shown in SEQ ID NO: 1, HCDR2 as shown in SEQ ID NO: 104, and HCDR3 as shown in SEQ ID NO: 105; LCDR1 as shown in SEQ ID NO: 29, LCDR2 as shown in SEQ ID NO: 30 and LCDR3 as shown in SEQ ID NO: 31 . Specifically, SEQ ID NO s : 1 , 2, and 103-105 of the instant claims are 100% identical to amino acid sequences within SEQ ID NO s: 38, 66, and 68 (this is not an exhaustive list of alignments, there are many more sequences within the prior art that have 100% alignment). SEQ ID NO: 29 of the instant claims is 100% identical to SEQ ID NO: 118 of the reference (but also appears within several other sequences, i.e. SEQ ID NOs: 4, 10, 12, 38, 40, 66, 68, 74, and 76) . SEQ ID NO: 30 of the instant claims is 100% identical to SEQ ID NO: 117 of the prior art reference. SEQ ID NO: 31 of the instant claim is 100% identical to SEQ ID NO: 116 of the prior art publication (as stated above, this is not an exhaustive list this sequence also appears within SEQ ID NOs: 12, 31, 68, 148, 168, 170, 172, 174 ,176, 178, 182, 186, 188, 190, 192, and 194 of the prior art) . The prior art further discloses these antibodies are humanized (pg. 31, line 29; pg. 32, line 13 through pg. 33, line 5). Regarding claim 6 , which is drawn to the antibody further comprising heavy chain constant region and/or light chain constant region, the Micromet AG publication teaches antibodies comprising a single chain (paragraph bridging pages 6-7) , namely, an antibody heavy chain (“VH region”) or an antibody light chain (“VL region”) . This teaches an antibody further comprising a heavy chain constant region and/or light chain constant region, as claimed. Regarding claim 9 , drawn to a monoclonal antibody, Figure 23 (and legend) teaches a monoclonal IgG antibody “ mAb I ” as described in Example 1 of the reference. Thus, the prior art teaches the monoclonal antibody of the claim. Regarding claim 10 , drawn to antigen binding fragments, Figures 22 and 23 (and legends) of the Micromet AG publication disclose scFv fragments, which teaches the Fv or ScFv fragments of the instant claim. Regarding claim 11 , drawn to multispecific or bispecific antibodies, Claims 1 and 16 of the Micromet AG publication prior art are directed to bispecific antibody products comprising the antibody of the claims. Regarding claim 12 , drawn to an isolated nucleic acid that encodes the light chain or heavy chain variable region, the Micromet AG publication discloses the nucleic acid sequences encoding the antibody of the claims (pg. 14, lines 1-6; and, for example, SEQ ID NO: 37 which encodes for SEQ ID NO:38 of the reference). Regarding claim s 13 and 14 , drawn to a vector and host cell comprising the nucleic acid encoding the antibody, p age 60 at example 5 and Claim 22 of the Micromet AG publication discloses expression vectors comprising the nucleic acid molecules encoding for the antibody of the claims , and expression in E. coli (“host cell” of the instant claim). Regarding claim 1 5 , drawn to a method of preparing the antibody, the Micromet AG publication discloses methods of preparing an antibody wherein it disclose expression in cultured E. coli and recov er ing of the antibody using cynomolgus peripheric blood monocytes that express CD3 (Example 3 spanning pgs. 58-59). Regarding claim 16 , drawn to an immunoconjugate comprising the antibody and “other substances, such as labels ” , the Micromet AG publication discloses Immunocomplexes wherein it discloses testing the antibodies for binding on antigens presented on HLA-DR haplotypes “e.g. fluorescence-labeled pepides of PBMCs” (pg. 33, lines 31-33). Regarding claim 17 , drawn to a pharmaceutical composition comprising the antibody, the Micromet AG publication discloses, “ the present invention relates to pharmaceutical compositions comprising bispecific single chain antibodies exhibiting cross-species specificity …” (Abstract). Regarding claim 18 , drawn to a pharmaceutical composition comprising the antibody and one or more therapeutic agents, the Micromet AG publication teaches “ uses of the bispecific antibody … according to the invention for the preparation of therapeutics ” (pg. 22, lines 11-12). The prior art discloses the antibody in combination with additional drug(s) (pg. 35, lines 3-26). Regarding claim 19 , drawn to treating a tumor comprising administering the antibody, the prior art teaches treating “tumorous disease … malignant disease, preferably cancer” (pg. 35, lines 3 —6). Regarding claim 20 , drawn to the method of claim 19 further comprising one or more therapies, as stated above the prior art teaches treating tumors comprising administering the antibody in conjunction with one or more additional drug(s) (pg. 35, lines 3-26). Regarding claim 21 , drawn to a method for detecting CD3 in a sample, Example 1 of the Micromet AG prior art teaches testing of the antibody to cell lines by flow cytometric analysis (pg. 44, lines 1-22). This anticipates the steps of the claim comprising contacting a sample with the antibody and detecting the formation of a complex between the antibody and CD3. Regarding claim 22 , drawn to a humanized anti-CD3 antibody comprising a mutation selected from those listed in the claim – the scope of which is unclear (see rejection above) , the Micromet AG publication teaches: “ The term ‘ humanized ’ or grammatically related variants thereof also encompasses cases in which, in addition to replacement of one or more CDR regions within a VH and/or VL of the first and/or second binding domain further mutation/s ( e.g. substitutions) of at least one single amino acid residue/s within the framework ("FR") regions between the CDRs has/have been effected such that the amino acids at that/those positions correspond/s to the amino acid/s at that/those position/s in the animal from which the CDR regions used for replacement is/are derived. As is known in the art, such individual mutations are often made in the framework regions following CDR-grafting in order to restore the original binding affinity of the non-human antibody used as a CDR-donor for its target molecule ” (pg. 32, lines 26-34). Therefore, the invention of the claims fails to distinguish over the antibody, nucleic acid products, and methods in the Micromet AG prior art publication, and claims 4, 6-7, and 9-22 are rejected under 35 U.S.C. 102 (a)(1), or in the alternative under 102(a)(2) . Conclusion No claim is allowed. Correspondence Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT STACEY NEE MACFARLANE whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-3057 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 7:30-5 (EST) & Sat. A.M. . 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Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /STACEY N MACFARLANE/ Examiner, Art Unit 1675