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 .
Applicant’s amendments and replies filed January 14 and January 15, 2026 have been received and entered into the case. Claims 66 and 76 are canceled; claims 80 – 81 are added; claims 60 – 65, 67 – 75, 77 – 81 are pending; claims 65, 67 – 75 and 78 – 79 are withdrawn; claims 60 – 64, 77 and 80 – 81 have been considered on the merits insofar as they read on the elected species, SEQ ID NO: 5.
Claim Objections
Claims 62, 77 and 80 are objected to because of the following informalities:
In claims 62 and 77, arginine is capitalized which is inconsistent with amended claim 61.
In claim 80, “carry” should read “carries” for consistency with claim 60.
Appropriate correction is required.
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 60 – 64, 77 and 80 – 81 remain/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.
Claims 60 – 64, 77 and 80 – 81 recite a mutant ADAMTS13 that caries “at least one mutation” and/or or “any truncated ADAMTS-13.” These claims are considered genus claims that encompass a wide array of mutants and truncated ADAMTS13. The specification fails to set forth a representative number of examples in order to reasonably verify possession of such a potentially enormous number of mutants and truncated ADAMTS13.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claims are broad generics, with respect to all mutants or any truncated ADAMTS13 that might result from a single substitution in ADAMTS13 or any truncation of ADAMTS13. The possible variations of mutations and truncated ADAMTS13 are limitless with potentially millions of resulting sequences.
The purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by them. A patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that the inventor invented the claimed invention. Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." The specification lacks sufficient variety of species of variants, mutants and/or derivatives to reflect this variance in the genus since the specification does not provide any examples of such a genus of mutants . Accordingly, the specification fails to provide adequate written description for the genus of mutant “that carries at least one mutation” and “any truncated ADAMTS-13” and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed had possession of the entire scope of the claimed invention Moreover, the specification neither describes the complete structure of a representative number of species, nor describes a representative number of species in terms of partial structure and relevant identifying characteristics. Absent of such teachings and guidance as to the structure and function of these variants, mutants and derivative, the specification does not describe the claimed variants, mutants or derivatives in such full, clear, concise and exact terms so as to indicate that Applicant had possession of these mutants at the time of filing of the present application.
Thus, the written description requirement has not been satisfied.
Response to Arguments
Applicant argues the specification describes the full scope of the claims since the claims require the mutants and truncated ADAMTS13 to display the function of “resistance and/or reduced sensitivity to cleavage and/or inactivation by at least one tissue plasminogen activator (tPA)” which is a “relevant identifying characteristic” to satisfy written description, per MPEP 2163 (II)(3)(a)(ii).
However, this argument fails to persuade. The only recited characteristic is the recited function. MPEP 2163 (II)(3)(a)(ii) specifically states that a functional characteristic must be coupled with a known or disclosed correlation between function and structure. In this regard, the claims fail to recite a particular structure that accomplishes the function. Without reciting the particular structure, materials or steps that accomplish the function or achieve the result, all means or methods of resolving the problem may be encompassed by the claim. Unlimited functional claim limitations that extend to all means or methods of resolving a problem is not adequately supported by the instant specification. It is noted that a single claim reciting a functional outcome covering every conceivable means for achieving the stated result fails to satisfy the written description requirement because the specification discloses only those means known to the inventor, and is not commensurate in scope with the claim. (MPEP 2173.05(g)).
Neither the claims nor the specification couples the argued function with a known or disclosed correlation between this function and the structure of the mutant ADAMTS-13 or truncated ADAMTS-13. The specification discloses substituting R312 or V313 as denoted by SEQ ID NO:2 (0032 of the published application). However, the specification shows that only one of four tested R312 V313 mutants exhibited resistance to cleavage by tPA (01114, example 4 of the published application). No examples are provided to evidence whether R312D, R312E or R312H exhibit the claimed activity. Regarding “any truncated ADAMTS-13,” example 4 further shows only one truncated substitute (trADAMSTS-13 R312K) demonstrates a longer half-life than the truncated or full-length wild type, and only two of the four variants tested exhibit resistance to tPA. Moreover, the specification fails to correlate the claimed function with any specific structure of the “any ADAMTS-13 mutant” or “any truncated ADAMTS-13.”
Thus, the written description requirement has not been satisfied.
This rejection can be overcome by limiting the claims to a mutant ADAMTS13 comprising the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:11.
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 60 – 64, 77 and 80 – 81 remain/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.
Claim 60 and its dependents remain/are drawn to a mutant ADAMTS13, however is rendered indefinite because it is unclear which of the claimed functions are recited in the alternative. For example, the claim appears to indicate the mutant has reduced resistance to cleavage by tissue plasminogen activator (tPA) or reduces inactivation by tPA. However, since ADAMTS13 is neither cleaved by nor inactivated by tPA, the language renders the phrases and claimed functions non-sensical. It is unclear what functions are required of the mutant and what mutants are included and excluded from the scope of the claims.
In claims 61, 62, 77, “the wild type ADAMTS-13” lacks proper antecedent basis.
In claim 62, “said adjacent amino acid residue” lacks proper antecedent basis.
Claim 62 remains indefinite for requiring R312K in SEQ ID NO: 5 because the sequence does not include the required substitute. In addition, the optional substitute of V313D is not present in SEQ ID NO:5. Rather, position 312 is arginine (R) and position 313 is tryptophan (W). It is unclear what variant is required by the claim. Clarification is required.
Response to Arguments
Applicant argues the rejection does not cite evidence that ADAMTS13 is not cleaved by tPA; and that applicant has newly discovered that tPA “most likely” cleaves ADAMTS13, pointing to example 1 which shows decreased ADAMTS13 activity in the presence of tPA.
Applicant is directed to DeYoung et al. (2025) which states: “ADAMTS13 was not cleaved by activated protein C, FVIIa, FIXa, FXIIa, or tPA” (p.2698). DeYoung shows that “plasma fibrinolysis assays resulted in substantial degradation of ADAMTS13 at various concentrations of tPA,” indicating the role tPA plays in fibrinolysis, e.g., converting plasminogen into plasmin. This is further supported by the definition of tPA as “an enzyme to convert plasminogen into its active form plasmin” (Wikipedia, Tissue-type plasminogen activator, pages 1, 3). Regarding example 1 of the instant application, the single example alone is insufficient to overcome the state of the art as it pertains to the mechanisms of and relationship between ADAMTS13, tPA and aprotinin.
Applicant further argues that positions 312 and 313 refer to a wild type sequence and the specification clearly references positions in the wild type. However, this argument fails to persuade because the claims fail to indicate these positions as corresponding to any specific sequence.
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.
Claims 60, 63 and 64 are rejected under 35 U.S.C. 102a1 and 102a2 as being anticipated by Zheng (US2015/0044171) as evidenced by DeYoung et al. (2022).
Regarding claim 60, Zheng teaches ADAMTS13 variants with at least one mutation (figures, claims), wherein the proteins display gain of function, retain activity and are resistant to autoantibody inhibition (resistance/reduced sensitivity to cleavage) (0037, example 1, claims). Since tPA does not cleave or inactivate ADAMTS13 (See DeYoung section 1.1, 1.3, 1.4 and also DeYoung 2025), the mutant is considered to display resistance/reduced sensitivity to cleavage and inactivation by tPA.
Regarding claim 63, the variant demonstrates increased activity (abstract, example 1, claims).
Regarding claim 64, Zheng teaches the ADAMTS13 variant in a pharmaceutically acceptable carrier (0009, 0038, claim 5).
Regarding claim 81, the variants have a MDTCS (fig.11, 22, example IV).
The reference anticipates the claimed subject matter.
Response to Arguments
Applicant states that claims 61, 62 and 67 are free of the prior art.
However, it is noted that no claims having been determined free of the prior art.
Applicant argues the ADAMTS13 of Zheng does not display resistance/reduced sensitivity to cleavage/inactivation by tPA; and that no evidence is provided to show tPA does not cleave/inactivate ADAMTS13.
However, in disclosing proteases that cleave ADAMTS13, DeYoung intentionally omits tPA and indicates tPA generates plasmin to cleave ADAMTS13 (1.4). In further support, applicant is directed to DeYoung et al. (2025) which states: “ADAMTS13 was not cleaved by activated protein C, FVIIa, FIXa, FXIIa, or tPA” (p.2698). DeYoung shows that “plasma fibrinolysis assays resulted in substantial degradation of ADAMTS13 at various concentrations of tPA,” indicating the role tPA plays in fibrinolysis, e.g., converting plasminogen into plasmin. This is further supported by the definition of tPA as “an enzyme to convert plasminogen into its active form plasmin” (Wikipedia, Tissue-type plasminogen activator, pages 1, 3). Regarding example 1 of the instant application, the single example alone is insufficient to overcome the state of the art as it pertains to the mechanisms of and relationship between ADAMTS13, tPA and aprotinin.
Applicant argues that Zheng teaches mutants only in the spacer domain which are excluded by the claims; and that applicant’s preferred embodiment has mutations in the disintegrin domain.
However, the rejected claims do not require these features. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant argues that DeYoung does not remedy these deficiencies.
However, DeYoung is relied upon for the sole purpose of showing tPA is known to not cleave ADAMTS13. It is maintained that Zheng teaches the features of the rejected claims.
No claims are allowed.
Conclusion
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 RUTH A DAVIS whose telephone number is (571)272-0915. The examiner can normally be reached Monday - Friday (8am - 4pm).
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/RUTH A DAVIS/ Primary Examiner, Art Unit 1699