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. Status of the Claims Claims 1-10 are examined herein. Claim Objections Claims 1-7 and 9-10 are objected to because: Claims 1 and 2 recite “the variants wherein”, should be “the variants, wherein”. Claim 3 recites “method as in claim 1 wherein”, should be “method as in claim 1, wherein”. Claim 4 recites “composition comprising of thiol variants”, should be “composition comprising [[of]] thiol variants”. Claim 5 recites “thiol variants comprises”, should be “thiol variants comprise”. Claims 5-7 and 9 recite “wherein the said”, should be “wherein said” or “wherein the”. Claim 10 recites “method as in claim 2 wherein”, should be “method as in claim 2, wherein”. 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 applicant regards as his invention. Claims 1-2 and 4-5 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 1-2 and 4-5 recite free cysteine and free cysteine variant, while the remaining claims recite cysteine residue(s). The terminology should be consistent; The term “free cysteine” is incorrect for referring to an unmodified cysteine residue; “free cysteine” is a free cysteine amino acid unincorporated into a protein. This is a basic nomenclature recognized in the art of protein chemistry. Redefining it creates significant confusion because free cysteine amino acids participate in cysteine residue cysteinylation. Claim 5 recites “variants selected from group comprising …”. The claim is indefinite because it uses the open “comprising” language. 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 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. Claims 1-3 and 10 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102 (a)(2) as being anticipated by Yen et al . (IDS; WO 2020150492) . Regarding claims 1-3 and 10 , Yen teaches a method for identifying free thiols in antibody molecules (pg. 9, lines 15-25). The method comprises sample preparation (labeling antibody with iodoacetyl groups, lines 17-18), subjecting the sample to ultra-performance liquid chromatography (UPLC), detecting the variant using high resolution mass spectrometry and identifying the variants wherein the thiol variants arise due to presence of free cysteines (UPLC-MS 2 system, lines 23-25). In a more detailed description of mass spectrometry analysis Yen teaches use of high-resolution mass spectrometry - “high resolution/high mass accuracy (HR/HA) fragment ion detection in the Orbitrap® mass analyzer” (pg. 13, lines 9-10). Yen teaches detection of free thiols in an antibody (pg. 9, line 15) , meeting the limitations of claim 1 reciting the thiol variants arise due to presence of free cysteines and claim 2 reciting the thiol variants arise include variants selected from free cysteine variant, because free thiols originate only from cysteine residues. As such, Yen necessarily teaches that the antibody has at least one cysteine residue, meeting the limitations of claims 3 and 10 . Claims 4-9 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102 (a)(2) as being anticipated by Ouyang et al . (CN109369806A; IDS provides abstract only). Regarding claim 4 , Ouyang teaches secukinumab (AIN457) as an anti-IL-17 monoclonal antibody ([0005]) and that “ secukinumab contains a free cysteine residue at position 97 of the light chain variable region. The free thiol group on this free cysteine residue is chemically very active and can react with a large number of substances, such as reacting with cysteine present in the culture system (i.e., cysteine modification), thereby forming a cysteine variant of secukinumab ” ([0006]). Ouyang’s teaching of free cysteine residue of secukinumab meets the limitation of claim 4 reciting thiol variants arising due to presence of free cysteine present in said antibody and claim 5 reciting the said thiol variants comprises of one or more variants selected from group comprising free cysteine variant. Regarding claim 6 , Ouyang’s teaching of the free cysteine residue at position 97 of the light chain variable region meets the limitation reciting one or more cysteine residue derived from a non-canonical cysteine. Cysteine residue at position 97 is a non-canonical cysteine residue because it does not participate in any disulfide bonds of the antibody molecule. The position of the residue inside the light chain variable region meets the limitation of claim 7 reciting the said non-canonical cysteine residue is in the CDR region of the light chain. Position 97 of the light chain meets the limitation of claim 8 reciting the said antibody has non-canonical cysteine is present at the 97th position of the light chain. Ouyang’s teaching of secukinumab (AIN457) as an anti-IL-17 monoclonal antibody ([0005]) meets the limitation of claim 9 reciting the said anti-IL-17A antibody is secukinumab . IL-17 and IL-17A are used interchangeably for designating the target of secukinumab . Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571) 272-1899 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 9:00AM-5:00PM (EST) . If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Bao-Thuy Nguyen can be reached on FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-0824 . 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 Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form. /ALEXANDER ALEXANDROVIC VOLKOV/ Examiner, Art Unit 1677 /REBECCA M GIERE/ Primary Examiner, Art Unit 1677