CYSTEINE PROTEASE

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 . DETAILED ACTION Claims 5, 6, 9-19, and 22-24 have been cancelled. Claims 1-4, 7, 8, 20, 21, and 25 are pending and under examination. Continued Examination Under 37 CFR 1.114 A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/17/2025 has been entered. Response to Arguments Applicant’s arguments, filed 12/17/2025, with respect to the rejection of claims 1, 3, 7, 8, 20, 21, and 25 under 35 USC 102, and the rejection of claim 2 under 35 USC 103, have been fully considered and are persuasive. Applicant has amended independent claim 1 to recite a polypeptide variant of SEQ ID NO:4 comprising a deletion of the first 20 amino acids at the N-terminus of SEQ ID NO:4 such that the variant does not include the contiguous sequence DDYQRNATEAYAKEVPHQIT, which is a limitation that is not taught by the prior art. Therefore, the rejections under USC 35 102 and 103 have been withdrawn. Claim Objections Claims 1, 2, 3, and 7 are objected to because of the following informalities: the claim and grammatical errors. Appropriate correction is required. See page 10 for a suggested claim amendment. Claim Rejections - 35 USC § 112(b) 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 1-4, 7, 8, 20, 21, and 25 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 and 2 recite a polypeptide comprising a variant of the sequence of SEQ ID NO:4, and then recite specific amino acid positions which correspond to SEQ ID NO:3. Therefore, it is unclear which positions of SEQ ID NO:4 should contain the claimed amino acids recited in items b) and c) of claim 1, and items 1-3 of claim 2. The claims should be amended to recite which amino acid positions of SEQ ID NO:4 contain the recited amino acids. Claims 3, 4, 7, 8, 20, 21, and 25 are also rejected as they depend from claim 1. A broad limitation together with a narrow limitation that falls within the broad 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. See MPEP § 2173.05(c). In the present instance, claim 2 recites the broad recitation of positively charged amino acids at residues corresponding to 138 or 139 SEQ ID NO:3, and the claim also recites wherein said positively charged amino acid is arginine or lysine which is the narrower statement of the limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Claim Rejections - 35 USC § 112(d) 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 2 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 2 recites that the polypeptide of claim 1 requires amino acid modifications recited in items 1-3. Claim 2 does not include all the limitations of claim 1, as the claim can be interpreted to require that the polypeptide of claim 1 comprises only the amino acid modifications recited in claim 2. Applicant may amend claim 2 to recite that the polypeptide further comprises amino acid modifications of items 1-3. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements. Claim Rejections - 35 USC § 112(a) 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 1-4, 7, 8, 20, 21, and 25 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. Claims 1 and 2 encompass a polypeptide with at least 80% sequence identity to instant SEQ ID NO:4. Claim 3 limits the polypeptide to a sequence that is at least 90%, 95%, or 99% identical to instant SEQ ID NO:4. Claim 4 limits the polypeptide to a sequence that comprises or consists of any one of SEQ ID NOs: 9, 17, or 19. Because claim 4 recites “the polypeptide…comprises”, the claim encompasses polypeptide sequences that comprise other amino acids in addition to SEQ ID NO:9, 17, or 19. Claim 7 is drawn to a polynucleotide encoding the polypeptide of claim 1. Claims 8, 20, and 21 are drawn to a host cell comprising the polynucleotide of claim 7. Claim 25 requires that the sequence identity to SEQ ID NO:4 is measured over residues 21-315. MPEP 2163.05 II states “the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that ‘only describe[d] one type of structurally similar antibodies’ that ‘are not representative of the full variety or scope of the genus.’). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us].’” The instant specification reduces to practice the activity of 4 polypeptide variants of SEQ ID NO:4, pCART197, 198, 200, and 201 (Figure 1; Example 1, p. 44), which are 93.6%-96% identical to instant SEQ ID NO:4. The specification does not disclose the entire genus of claimed IgG-specific cysteine proteases. The instant specification does not disclose what structural properties are required for the enzyme to maintain its activity, or disclose which regions of SEQ ID NO:4 are the active site residue(s) for conserving the claimed enzyme activity. Therefore, the disclosed species are not representative of the entire genus of claimed variants. Lannergard et al., (IdeE, an IgG-endopeptidase of Streptococcus equi ssp. equi. FEMS Microbiology Letters, 262: 230-235) teaches IgG-specific proteases IdeE and IdeZ (Abstract) deposited under GenBank Accession Numbers DQ508733 and DQ826037, respectively. GenBank Accession Number DQ508733 (IdeE) teaches a sequence that shares 99.5% sequence identity with instant SEQ ID NO:4, while GenBank Accession Number DQ826037 (IdeZ) teaches a sequence that shares 99.2% sequence identity with instant SEQ ID NO:4. However, Lannergard does not disclose enzyme active site residues or homologs with up to 20% sequence divergence from instant SEQ ID NO:4 that maintain IgG-specific cysteine protease activity. In summary, neither the instant specification, nor the prior art, discloses a structure-function relationship between conserved amino acid residues in the claimed enzyme structure and the claimed IgG-specific cysteine protease activity. One of ordinary skill in the art cannot reasonably predict which residues of SEQ ID NO:4 may be modified to generate a functional enzyme. Based on the instant disclosure, those skilled in the art would not conclude that the applicant was in possession of all claimed variants. Allowable Subject Matter The closest prior art reference is that of Lannergard et al., (IdeE, an IgG-endopeptidase of Streptococcus equi ssp. equi. FEMS Microbiology Letters, 262: 230-235; cited in the Final rejection mailed 09/19/2025). Lannergard teaches IgG-specific proteases IdeE and IdeZ (Abstract) deposited under GenBank Accession Numbers DQ508733 and DQ826037, respectively. GenBank Accession Number DQ508733 (IdeE) teaches a sequence that shares 99.5% sequence identity with instant SEQ ID NO:4 (see alignments below). PNG media_image1.png 546 646 media_image1.png Greyscale GenBank Accession Number DQ826037 (IdeZ) teaches a sequence that shares 99.2% sequence identity with instant SEQ ID NO:4 (see alignments below). PNG media_image2.png 560 652 media_image2.png Greyscale However, Lannergard, and no other prior art reference, teaches the sequence of SEQ ID NO:4 wherein amino acids 1-20 are deleted such that the polypeptide does not contain the contiguous sequence DDYQRNATEYAKEVPHQIT. Under BRI, it is interpreted that claim 1 requires that SEQ ID NO:4 contains: a lysine at residue 58, a cysteine at residue 68, a histidine at residue 238, and aspartic acids at residues 260 and 262. It is interpreted that claim 2 requires that SEQ ID NO:4 contains: positively charged amino acids at residues 104, 105; and, at least one of the following of: a deletion of leucine and threonine at residues 30 and 31, respectively; a substitution of threonine at residue 36; a deletion of tyrosine at residue 37; a substitution of glutamine at residue 38; a substitution of glycine at residue 39; a substitution of alanine at residue 33; or, a substitution of asparagine at residue 34. Therefore, to obviate the above rejections, Applicant may consider the following amendment, which has been drafted by the Examiner: 1. A polypeptide having IgG-specific cysteine protease activity and the amino acid wherein said polypeptide aresidue 68 b: at residue 58, a histidine (H) at residue 238, an aspartic acid (D) at residue 260, and an aspartic acid (D) at residue 262 and c1-20sequence 2. The polypeptide according to claim 1, further comprising: (1) residue 104 (2) residue 105 (3) i) a deletion of at residues 30 and 31, respectively ii) a threonine (T) in place of residue 36 iii) a deletion of residue 37 iv) a glutamine (Q) in place of residue 38 v) a glycine (G) in place of the asparagine (N) at residue 39 vi) an alanine (A) in place of residue 33 vii) an asparagine (N) in place of residue 34 3. Cancelled. 4. The polypeptide according to claim 1, which further includes an additional methionine at the N terminus and/or a histidine tag at the C terminus. 7. A polynucleotide or expression vector which comprises a nucleic acid sequence encoding the 25. Cancelled. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST. 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, Louise Humphrey can be reached at (571) 272-5543. 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. /LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657 /RACHEL EMILY MARTIN/Examiner, Art Unit 1657