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 .
Response to Amendment
Applicant’s remarks and amendments received 07/22/2026 have been acknowledged. Claims 1 and 2 have been amended. Claim 3 has been canceled. The claim amendments overcome the 35 USC 112(a) written description rejection previously set forth in the Non-Final Rejection of 04/22/2026.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings particularly Figure 1A are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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 1, 2, 11, and 15 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The nature of the invention relates to a DARPin molecule (SEQ ID NO: 1) which binds to and inhibits the ubiquitin-binding zinc finger domain of histone deacetylase 6 (HDAC6) as well as its use in treating viral infections (see Field of the Invention and Summary of the Invention, Pages 1 and 2 of the Specification).
Claim 1 is broadly drawn to a recombinant binding protein comprising N and C-terminal capping modules and an ankyrin repeat domain comprising amino acids 31 to 123 of SEQ ID NO: 1. wherein the recombinant binding protein specifically binds to HDAC6 and blocks the ubiquitin-engaging zinc finger domain of HDAC6.
Claim 2 broadens the ankyrin repeat domain to comprise amino acid 25 to 129 of SEQ ID NO: 1.
Thus, claims 1 and 2 encompass DARPin molecules having ankyrin repeat domains limited to amino acids 31 to 123 of SEQ ID NO: 1 or amino acids 25 to 129 of SEQ ID NO: 1
The specification teaches the identification of DARPins and nanobodies specifically binding to purified human HDAC6 zinc finger domain. Among the numerous binding molecules identified, only one single DARPin—F10 having the amino acid sequence of SEQ ID NO:1 (presently claimed)— was identified as having the desired biological property of blocking the ubiquitin-engaging zinc finger domain of HDAC6 both in vitro and in vivo. Further, it was shown that DARPin F10 impairs IAV infection and inhibits zika virus (ZIKV) infection (Page 2: 1st paragraph under Summary of the Invention, Pages 5-8: Description of the Figures, and Examples: Pages 21-25). While the specification demonstrates functional activity for the full-length DARPin of SEQ ID NO: 1, there does not appear to be any evidence or guidance to establish that DARPin having amino acids 31 to 123 of SEQ ID NO: 1 or, more broadly, amino acids 25 to 129 of SEQ ID NO: 1 is sufficient for binding to HDAC6 and inhibiting the ubiquitin-engaging zinc finger domain of HDAC6 commensurate in scope of claims 1 and 2. Further, there is no guidance provided in the specification on identifying recombinant binding proteins that are truncations of the DARPin F10 (SEQ ID NO: 1) and having the functional properties set forth in the claims.
The prior art teaches that DARPins are derived from natural ankyrin repeat proteins consisting of stacked repeat units, and multiple ankyrin repeats that contribute to their structure and binding function of DARPins (see Minter et al, in particular, Para. 0004-0005, of record). Sequence alterations in DARPin ankyrin repeats can impact their structure and binding properties. For example, a study of a HER2-binding DARPin found that a single His-to-Tyr substitution at framework position 52 altered inter-repeat hydrogen bonding and caused a significant conformational change that affected binding kinetics (Zahnd et al, see Abstract). Thus, the effect of changes to the ankyrin repeat sequence on DARPin structure and functional activity is not necessarily predictable. In this case, the ankyrin repeat domain is defined by amino acids 31 to 123 of SEQ ID NO: 1 or, more broadly, amino acids 25 to 129 of SEQ ID NO: 1. Without further evidence, the record does not establish that the recited subsequences of SEQ ID NO: 1 are sufficient to maintain the functional activity of the claimed DARPin recited in the claims.
A person of ordinary skill in the art at the time of filing would have had experience in antibody mimetics, protein engineering, and screening techniques. Even at this high level of skill, however, a DARPin structure having a truncated ankyrin repeat domain does not predictably result in a structure capable of binding to HDAC6 and blocking the ubiquitin-engaging property of HDAC6 at least not in the absence of additional screening and testing. Indeed, as noted in the specification, the generation of DARPins inhibiting the ubiquitin-binding property of HDAC6 was not a straightforward process. Thus, the level of skill does not obviate the need for additional experimentation across the full scope of the claimed genus especially in the absence of additional guidance provided in the specification or prior art. Claims 11 and 15, which depend on claim 1, do not cure the deficiencies of claim 1 and are thus also rejected.
Therefore, the specification is not enabled over the full scope of the claims.
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 1 recites that the recombinant protein comprises an ankyrin repeat domain having amino acids 31 to 123 of SEQ ID NO: 1. However, claim 2, which depends on claim 1, recites that the ankyrin repeat domain comprises amino acids 25 to 129 of SEQ ID NO: 1, adding additional amino acids to the ankyrin repeat domain. Thus, claim 2 fails to further limit the scope of the independent claim. 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.
Response to Arguments
Applicant's arguments filed 07/22/2026 have been fully considered but they are not persuasive.
With respect to 35 USC 112(a) enablement rejection, Applicant argues the following:
The specification enables a person of ordinary skill in the art to make and use the claimed recombinant binding protein without undue experimentation. The specification discloses the designed ankyrin repeat protein (DARPin) F10 having the amino acid sequence of SEQ ID NO:1. Expression and purification of DARPin F10 are described on pages 21-22, and the binding and functional properties of the recombinant binding protein are demonstrated in the Examples. The specification further provides guidance regarding the structure and selection of suitable capping modules. As described on page 13, a capping module is a polypeptide fused to the N- or C-terminal repeat module of a repeat domain that forms tight tertiary interactions with the repeat module and shields the hydrophobic core of the repeat module from solvent. The specification further explains that such capping modules may be derived from naturally occurring repeat proteins and identifies WO 02/020565 as describing capping modules and capping repeats. In addition, the Examiner's reliance on Minter et al. confirms that N-terminal and C-terminal capping modules associated with ankyrin repeat domains were well known in the art.
Enablement requires that the specification describe how to make and use the invention. The specification provides such guidance by disclosing the DARPin F10 scaffold, describing the structure and function of capping modules, and demonstrating the preparation and functional characterization of recombinant binding proteins. The ankyrin repeat domain comprising amino acids 31 to 123 of SEQ ID NO:1 is disclosed in the specification, and recombinant binding proteins containing this ankyrin repeat domain are exemplified and tested. In addition, capping modules associated with ankyrin repeat proteins were known structural elements in the art. Based on the teachings of the specification and the knowledge in the art, one of ordinary skill could have made the claimed recombinant binding protein without undue experimentation.
In response to Applicant’s arguments, While the specification demonstrates functional activity for the full-length DARPin of SEQ ID NO: 1, there does not appear to be any evidence or guidance to establish that DARPin having amino acids 31 to 123 of SEQ ID NO: 1 or, more broadly, amino acids 25 to 129 of SEQ ID NO: 1 is sufficient for binding to HDAC6 and inhibiting the ubiquitin-engaging zinc finger domain of HDAC6 commensurate in scope of claims 1 and 2. Applicant has not established whether the recited subsequences of SEQ ID NO: 1 represent the complete ankyrin repeat domain of the full-length DARPin or instead represent a truncation of the ankyrin repeat domain. If, for the sake of argument, amino acids 25 to 129 of SEQ ID NO: 1 represents the entire ankyrin repeat domain present in SEQ ID NO: 1, then a sequence comprising amino acids 31 to 123 of SEQ ID NO: 1 is a truncation of the ankyrin repeat domain; yet, it does not appear that the specification provides data showing that a DARPin having an ankyrin repeat domain limited to amino acids 31 to 123 of SEQ ID NO: 1 exhibits the recited functional properties.
Therefore, the 35 USC 112a enablement rejection is maintained in view of the claim amendments.
Conclusion
No claims are allowable.
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.
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/LIA E TAYLOR/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
