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 the invention of Group I, drawn to a recombinant binding protein comprising at least 90 consecutive amino acids of SEQ ID NO: 1 (claims 1-3, 11, and 15) in the reply filed on 02/10/2026 is acknowledged.
Claims 4-8, 12-13, and 16-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/10/2026.
Claims 1-3, 11, and 15 are examined on the merits in the present Office Action.
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.
Written Description
Claims 1-3, 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 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 1 and 2 encompass truncated DARPin constructs lacking one or both of the N-and C-terminal caps and missing essential amino acids within the repeat domains. Such structures are not reasonably correlated with the function of binding to HDAC6 and blocking the ubiquitin-engaging zinc finger domain of HDAC6. Claims 11 and 15, which depend from claim 1, do not cure the deficiencies of claim 1 and are thus also rejected.
Claim 3 does not recite the amino acid sequence of any recombinant binding protein having the functional property of competing with the recombinant binding protein of claim 1 for binding to HDAC6 and blocking the ubiquitin-engaging zinc finger domain of HDAC6.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by 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 genus (MPEP 2163).
In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin [e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting at 1171, 25 USPQ2d at 1606). Also see (CAFC 2002). Enzo-Biochem v. Gen-Probe Fiers, 984 F.2d 01-1230.
Claim 1 is broadly drawn to a recombinant binding protein comprising at least 90 consecutive amino acids of SEQ ID NO: 1 (length = 157 aa), wherein the recombinant binding protein specifically binds to HDAC6 and blocks the ubiquitin-engaging zinc finger domain of HDAC6.
Claim 2 further limits the recombinant binding protein to comprise at least 120 consecutive amino acids 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). However, there does not appear to be any evidence provided in the specification that a truncated DARPin having at least 90 or 120 consecutive amino acids 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. While Applicant has provided an example of a DARPin (F10, SEQ ID NO: 1) having the claimed functional properties, such disclosure does not adequately represent the structural diversity of the claimed genus of truncated recombinant binding proteins having the functional properties of binding to HDAC6 and inhibiting the ubiquitin-engaging zinc-finger domain of HDAC6.
It is known in the art that DARPins are derived from natural ankyrin repeat proteins, which consists of stacked repeat units that form a rigid protein domain. These ankyrin repeat modules have been engineered using a consensus design approach. Each repeat contains seven variable positions and constructs typically have three repeats. The repeats are flanked by N-and C-terminal capping regions that seal the hydrophobic core and are essential for proper folding within the cell. Additionally, the N and C-caps contain many negatively charged residues, which contribute to the overall stability of the protein and prevention of aggregation (see Minter et al, in particular, Para. 0004-0005). As such, the overall DARPin structure is critical for maintaining protein stability and enabling antigen binding. The structure of truncated DARPins as encompassed by claims 1 and 2— lacking either or both the N-and C-terminal caps or missing essential amino acids with the repeat domains—are thus not correlated with the functional property of binding to HDAC6 and blocking the ubiquitin-engaging zinc finger domain of HDAC6. Further, there is no guidance provided in the specification on identifying recombinant binding proteins that are truncations of the DARPin of SEQ ID NO: 1 having the recited functional properties set forth in the claims. Without further guidance, artisans would have to perform additional screening and testing to identify the recombinant binding proteins encompassed by claims 1 and 2 having the functional property of binding to HDAC6 and blocking the ubiquitin-engaging zinc finger domain of HDAC6. Claims 11 and 15, which depend from claim 1, do not cure the deficiencies of claim 1 and are thus also rejected.
Claim 3 is broadly drawn to a recombinant binding protein having the functional property of competing with the recombinant binding protein of claim 1 for binding to HDAC6 and blocking the ubiquitin-engaging zinc finger domain of HDAC6. As presently written, the claim fails to recite any structural features for the broad genus of recombinant binding proteins having the recited functional property. As stated previously, while an example of a DARPin (F10, SEQ ID NO: 1) having the claimed functional properties has been provided, such disclosure does not adequately represent the structural diversity of the claimed genus of recombinant binding proteins that can compete with F10 or truncations thereof for binding to HDAC6 and blocking the ubiquitin-engaging zinc finger domain of HDAC6. Additionally, there is insufficient guidance provided in the specification for identifying members of the genus recombinant binding proteins encompassed by claim 3.
Therefore, the claimed genus of recombinant binding proteins lacks adequate written description because there does not appear to be any correlation between the structure of the claimed recombinant binding proteins that are truncations of the DARPin F10 (SEQ ID NO: 1) and the function of binding to HDAC6 and inhibiting the ubiquitin-engaging zinc-finger domain of HDAC6. Similarly, there is insufficient correlation between the structure of recombinant binding proteins that compete with F10 or truncations thereof for binding. Thus, one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genera at the time the instant application was filed.
Scope of Enablement
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, because the specification, while being enabling for a fully-defined recombinant binding protein of SEQ ID NO: 1 (the DARPin clone F10) does not reasonably provide enablement for recombinant binding proteins that truncations of the DARPIn clone F10 (SEQ ID NO: 1). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
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 at least 90 consecutive amino acids of SEQ ID NO: 1 (length = 157 aa), wherein the recombinant binding protein specifically binds to HDAC6 and blocks the ubiquitin-engaging zinc finger domain of HDAC6.
Claim 2 further limits the recombinant binding protein to comprise at least 120 consecutive amino acids 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). However, there does not appear to be any evidence provided in the specification that a truncated DARPin having at least 90 or 120 consecutive amino acids 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, which consists of stacked repeat units that form a rigid protein domain. These ankyrin repeat modules have been engineered using a consensus design approach, resulting in a standardized repeat unit. Each repeat contains seven variable positions and constructs typically have three repeats. The repeats are flanked by N-and C-terminal capping regions that seal the hydrophobic core and are essential for proper folding within the cell. Additionally, the N and C-caps contain many negatively charged residues, which contribute to the overall stability of the protein and prevention of aggregation (see Minter et al, in particular, Para. 0004-0005). As such, the overall DARPin structure is critical for maintaining protein stability and enabling antigen binding. A truncated DARPin encompassed by claims 1 and 2 lacking either or both the N-and C-terminal caps or missing essential amino acids with the repeat domains is not reasonably expected to maintain proper folding or to retain binding to the target antigen HDAC6.
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, truncation of the DARPin structure 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 DARPisn 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.
Therefore, the specification is not enabled over the full scope of the claims.
Conclusion
No claims are allowable.
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/LIA E TAYLOR/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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