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. Election/Restrictions Applicant’s election without traverse of claims 1-9, and the election of species SEQ ID NO: 51 and SEQ ID NO: 61, in the reply filed on 12/15/2025 is acknowledged. Claim s 6-7, 10-14, and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and species , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/15/2025 . In view of the prior art search, the species election is expanded to include SEQ ID NOs: 57 and 152. Priority This application is a 371 of PCT/GB2022/050427 ( 2/17/2022 ) which claims priority to GB2102208.2 ( 2/17/2021 ) as reflected in the filing receipt issued on 11/7/2024 . Information Disclosure Statement The information disclosure statement (IDS) filed on 8/16/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. 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. Claim 8 is 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. Regarding written description, 35 U.S.C. 112(a) and the first paragraph of pre- AlA 35 U.S.C. 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co. , 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010). To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention (MPEP § 2163(I)). MPEP 2163(II)(A)(3)(a)(i and ii) states that 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, reduction to drawings, 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. A "representative number of species" means that the species which are adequately described are representative of the entire genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc ., .759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, claim 8 is directed to an ADAMTS 13 variant comprising an amino acid sequence having at least 60% identity to elected SEQ ID NO: 61. There is not sufficient written description support for an amino acid sequence having 60% identity to SEQ ID NO: 61 which maintains enzyme function. As set forth in the instant specification, p. 61, a “variant” refers to a protein that shares sequence identity and maintains the ability to perform a function performed by the reference protein. However, there is no disclosure of which regions or structural elements of SEQ ID NO: 61 are required or essential for activity, and which regions can be modified, to produce a variant having the recited sequence identity and enzyme function. SEQ ID NO: 61 has 1353 amino acid residues. This means that anywhere from 1-541 residues may be substituted or modified, with 19 potential amino acids at any given position, within the scope of 60% identity. Thus, 60% identity encompasses a vast number of potential sequences, and it would not be clear to a skilled artisan which of these potential variants would retain enzyme function. There are no examples in the specification directed to variants of SEQ ID NO: 61, other than the specifically claimed substitutions (i.e., recited in claims 2-5), which retain the claimed activity, or any indication of which residues can or cannot be modified. For this reason, it is not clear that applicant was in possession of the full scope of the invention, a functional ADAMTS13 enzyme having a sequence with 60% identity to SEQ ID NO: 61. Thus, claim 8 fails to comply with the written description requirement. 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. Claim 3 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. SEQ ID NOs: 50 and 156 comprise the L3 subregion of ADAMTS13, with a sequence X 1 X 2 X 3 X 4 GRTTAT X 5 AGASLEWSQARGLLFS X 6 A X 7 Q X 8 RRLL X 9 G X 10 (see specification Sequence Table pp. 12-13, 58). X 1 -X 10 correspond to positions A1144, A1145, A1146, P1147, P1154, P1171, P1173, P1175, P1180, and P1182 in the WT ADAMTS13 sequence, respectively. In both SEQ ID NOs: 50 and 156, X 1 - X 3 may be A and X 4 - X 10 may be P (see specification Sequence Table pp. 12-13, 58 ; instant SEQ ID NO: 1 ). If X 1 - X 3 in SEQ ID NOs: 50 and 156 are A and X 4 - X 10 are P, this is the same as the WT SEQ ID NO: 48. However, the ADAMTS13 variant of claim 1 requires at least one substitution in the region corresponding to SEQ ID NO: 48 (see Sequence Table p. 12). Therefore, it is unclear whether SEQ ID NOs: 50 and 156 require a substitution in the region corresponding to SEQ ID NO: 48 or not, as the variable amino acids may be the same as the wild type amino acids at those positions. For this reason, claim 3 is indefinite. The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.— Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 3 recites SEQ ID NOs: 50 and 156. As discussed in the rejection under 35 U.S.C. § 112(b) above, SEQ ID NOs: 50 and 156 have variable amino acids at the positions recited in claim 2. However, variable positions X 1 - X 3 may be A and X 4 - X 10 may be P, making SEQ ID NOs: 50 and 156 identical to the wildtype sequence (see specification Sequence Table pp. 12-13, 58). As claim 1, upon which claim 3 depends, requires a substitution in the region corresponding to SEQ ID NO: 48, claim 3 does not further limit claim 1 as it includes sequences that are identical to the WT in the region according to SEQ ID NO: 48 (i.e., do not have a substitution). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Rejections - 35 USC § 102 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 8-9 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Roose et al., TH Open ; 2(01 ):e 8-15. Regarding claim 1, Roose teaches human ADAMTS13 with a substitution at residue 1177 (R1177Q) relative to the wildtype sequence ( Roose “Abstract”; p. e10 “Expression of Wild Type (WT), p.A900V, p.R1177Q, and p.A900V/R1177Q ADAMTS13”). Residue 1177 is located in the third linker region of the ADAMTS13 sequence ( Roose p. e11 “ADAMTS13-Related Parameters in Acute and Remission Samples” para. 2). Instant SEQ ID NO: 48 corresponds to the linker 3 region of the WT ADAMTS13 sequence , residues 1131 to 1190 (see instant specification p. 66 lines 13-16). The substitution at position 1177 as taught by Roose is therefore in the region corresponding to SEQ ID NO: 48 relative to the wild-type sequence, in the linker 3 region between residues 1131-1190. Regarding claim 3, SEQ ID NOs: 50 and 156 have variable amino acids at the positions recited in claim 2. Variable positions X 1 - X 3 may be A, and positions X 4 - X 10 may be P, making SEQ ID NOs: 50 and 156 identical to the wildtype sequence (see specification Sequence Table pp. 12-13, 58; instant SEQ ID NO: 1). Therefore, SEQ ID NOs: 50 and 156 include the wildtype ADAMTS13 sequence. Roose teaches wildtype human ADAMTS13 ( Roose p. e10 “Expression of Wild Type (WT), p.A900V, p.R1177Q, and p.A900V/R1177Q ADAMTS13”). Regarding claim 8, instant SEQ ID NO: 61 is 99.9% identical to the WT ADAMTS13 sequence ( see WT ADAMTS13 sequence, instant SEQ ID NO: 1 ). The variant sequence taught by Roose differs from the WT by 1 amino acid, R1177Q. Thus, the variant taught by Roose has a sequence that is over 60% identical to SEQ ID NO: 61. Regarding claim 9, the limitation “displays increased proteolytic activity as compared to wildtype human ADAMTS13” is a functional limitation of the ADAMTS13 variant of claim 1. Roose teaches an ADAMTS13 variant according to claim 1 as discussed above. Claim 1 encompasses ADAMTS13 variants with substitutions at any position in the linker 3 (SEQ ID NO: 48) region. Absent any missing essential unclaimed features, any ADAMTS13 variant having the structure of claim 1 must have the function of increased proteolytic activity as compared to wildtype human ADAMTS13. Therefore, the ADAMTS13 variant of Roose reads on claim 9. Claims 1, 2, and 8-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Scheiflinger et al., US 7,763,430 B2. Regarding claim 1, Scheiflinger teaches von Willebrand Factor-cleaving protease (“ vWF -cp”, or ADAMTS13) proteins ( Scheiflinger col. 1 lines 19-34). SEQ ID NO: 6 according to Scheflinger is 98 .3 % identical to instant SEQ ID NO: 48, with one amino acid substitution (see sequence alignment below ). Regarding claim 2, SEQ ID NO: 6 of Scheiflinger comprises a substitution at position 43 of SEQ ID NO: 48 (see sequence alignment below ). As set forth on p. 62 of the instant specification, SEQ ID NO:48 corresponds to positions 1131 to 1190 of SEQ ID NO:1 (wildtype ADAMTS13), with the alanine residue at position 14 of SEQ ID NO:48 corresponding to position 1144 of the WT sequence. Therefore, position 43 of SEQ ID NO: 48 corresponds to position 1173 of the WT sequence, and SEQ ID NO: 6 of Scheiflinger comprises a substitution at position P 1173. Regarding claim 8, instant SEQ ID NO: 61 is 99.9% identical to the WT ADAMTS13 sequence (see WT ADAMTS13 sequence, instant SEQ ID NO: 1). The variant sequence taught by Scheiflinger differs from the WT by 1 amino acid, P1173R. Thus, the variant taught by Scheiflinger has a sequence that is over 60% identical to SEQ ID NO: 61. Regarding claim 9, the limitation “displays increased proteolytic activity as compared to wildtype human ADAMTS13” is a functional limitation of the ADAMTS13 variant of claim 1. Scheiflinger teaches an ADAMTS13 variant according to claim 1 as discussed above. Absent any missing essential unclaimed features, any ADAMTS13 variant having the structure of claim 1 must have the function of increased proteolytic activity as compared to wildtype human ADAMTS13. Therefore, the ADAMTS13 variant of Scheiflinger reads on claim 9. Claim Rejections - 35 USC § 103 The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claims 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Scheiflinger et al. as applied to claims 1, 2, and 8-9 above, in view of Zhang et al., Journal of molecular evolution ; 50(1):56-68. Scheiflinger teaches an ADAMTS13 protein with a substitution of proline for arginine at position 1173. Scheiflinger does not teach a substitution of proline to valine, isoleucine, or lysine. Regarding claim 4, Zhang teaches that amino acids are classified into groups based on physicochemical properties, and substitutions of amino acids within groups are considered conservative, whereas substitutions between groups are radical (Zhang p. 56 para . 1). A conservative substitution would be expected to maintain the physiochemical properties of the amino acid and therefore result in minimal change to the protein. Zhang teaches that proline, valine, and isoleucine are all neutral, nonpolar amino acids (Zhang p. 57 Fig. 1). Therefore, a substitution of proline to valine or isoleucine would be considered conservative and would not result in a change in physiochemical properties. It would have been obvious for a skilled artisan , with a reasonable expectation of success, to substitute the proline at position 1173 in the WT ADAMTS13 protein with a valine or isoleucine. Scheiflinger teaches substitution of the proline at this position of ADAMTS13 , and a skilled artisan would therefore recognize that this position may be substituted . Substitution of proline to valine or isoleucine would be a conservative substitution, as taught by Zhang. Thus, introducing a substitution of valine or isoleucine at this position would be considered a simple substitution of one known element for another having similar properties, with a reasonable expectation that such a substitution would result in a protein having similar properties to the wildtype. Regarding claim 5, instant SEQ ID NO: 57 is an ADAMTS13 variant L3 region with a substitution of P1173V, and SEQ ID NO: 152 is an ADAMTS13 variant L3 region with a substitution of P1173I . As discussed above, it would have been obvious to make these mutations in view of the teachings of Scheiflinger and Zhang. Therefore, an ADAMTS 13 variant comprising the amino acid sequence of SEQ ID NO: 57 or 152 is obvious in view of the prior art. Allowable Subject Matter It appears that the elected species, an ADAMTS13 variant comprising the amino acid sequence of SEQ ID NO: 51 (i.e., A1144 substitution) is free of the prior art. The closest prior art is Roose et al. and Scheiflinger et al. Roose teaches an ADAMTS13 variant with a substitution in the region according to SEQ ID NO: 48, but does not teach a substitution at position A1144. Scheiflinger teaches a substitution at position 1173, but not A1144. The prior art does not appear to teach a sequence corresponding to SEQ ID NO: 51, or an ADAMTS13 variant with a substitution at the position corresponding to A1144. Conclusion Claims 1- 5 and 8- 9 are rejected. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT EMILY F EIX whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-0808 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8am-5pm ET . 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, FILLIN "SPE Name?" \* MERGEFORMAT Sharmila Landau can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571)272-0614 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. 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. /EMILY F EIX/ Examiner, Art Unit 1653 /JENNIFER M.H. TICHY/ Primary Examiner, Art Unit 1653