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
The amendment to the claims filed after non-final office action on April 6, 2026 is acknowledged. Claims 1, 3-11, 13-14, 19-, 21-23, 25-27 were amended, claims 2, 12, 15-18, 20, 28 were canceled and claims 1, 3-11, 13-14, 19, 21-27 are pending in the instant application. The restriction was deemed proper and made final previous office action. Applicants argue that claims 3-5 should be rejoined and should have been previously examined as they read on the elected species. Applicants election argument has been considered but not found persuasive. Applicant’s contention that claims 3-5 should be examined because they fall within the scope of the broader HD1-derivative genus is not persuasive. Applicant elected the specific species of SEQ ID NO:1, not the entire genus represented by SEQ ID NO:9. Claims 3-5 recite distinct substituted peptide species that do not read on the elected species and therefore remain withdrawn. Such claims will be eligible for reconsideration and rejoinder if the application is otherwise found allowable and the requirements for rejoinder are satisfied.
Furthermore, regarding Applicants arguments that the reference used to break unity of invention was not proper, the propriety of the restriction requirement is determined based on the claims pending at the time the requirement was made. At that time, the claims encompassed distinct inventions/species such that restriction was proper. Applicant’s subsequent amendment of the claims does not retroactively render the restriction requirement improper. Accordingly, the restriction requirement is maintained. Withdrawn claims will be considered for rejoinder, if appropriate, upon allowance of the elected invention.
Claims 3-5, 10, 19, 21-27 are withdrawn as being drawn to a non-elected species/invention. Claims 1, 6-9, 11, 13-14 are examined on the merits of this office action.
Withdrawn Rejections/Objections
The objection to the drawings is removed in view of amendment of the drawings filed April 6, 2026 to include respective SEQ ID Nos.
The rejection of claims 1-2, 6-9, 11, 14, 28 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 is withdrawn in view of amendment of the claims filed April 6, 2026.
The rejection of claim 2 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 is withdrawn in view of amendment of the claims filed April 6, 2026.
The rejection of claim(s) 1 under 35 U.S.C. 102(a)(1) as being anticipated by Fontana (W02002079243 A2) is withdrawn in view of amendment of the claims filed April 6, 2026.
The rejection of claim(s) 1 and 14 under 35 U.S.C. 102(a)(1) as being anticipated by Mitcham (WO2003033515 A1) is withdrawn in view of amendment of the claims filed April 6, 2026.
The rejection of claim(s) 1 and 6 under 35 U.S.C. 103 as being unpatentable over Fontana (W02002079243 A2) is withdrawn in view of amendment of the claims filed April 6, 2026.
The rejection of claim(s) 1, 6-8, 14 are rejected under 35 U.S.C. 103 as being unpatentable over Mitcham (WO2003033515 A1) is withdrawn in view of amendment of the claims filed April 6, 2026.
Maintained Objection to Sequence Listing
The sequence listing submitted on April 6, 2026 is objected to because it does not comply with the sequence listing requirements applicable to the present application. The present application is subject to the sequence listing requirements of 37 CFR 1.821-1.825 (WIPO Standard ST.25). Applicant has submitted a sequence listing in WIPO Standard ST.26 format. The submitted ST.26 sequence listing is not compliant with the sequence listing requirements applicable to this application. Applicant is required to submit a replacement sequence listing in compliance with 37 CFR 1.821-1.825 (ST.25). In addition, the submitted sequence listing does not appear to include the amino acid sequences recited in claim 1, limitations (ix)-(xiii). Claims 1(ix)-(xiii) recite amino acid sequences of defined length having specified amino acid residues at identified positions. Such sequences constitute amino acid sequence disclosures and must be included in the sequence listing in accordance with 37 CFR 1.821 et seq. Applicant is required to provide a compliant sequence listing including the amino acid sequences recited in claim 1(ix)-(xiii).
Further, the application contains inconsistent sequence information. Figure 17 identifies SEQ ID NO:35 as the amino acid sequence GSGTSGSS, whereas the submitted sequence listing identifies SEQ ID NO:35 as MDWWAMWPSL. Applicant is required to correct the inconsistency between the sequence listing and the application disclosure and clearly identify the amino acid sequence corresponding to SEQ ID NO:35. Correction of the foregoing deficiencies is required.
Maintained/Revised Rejection
Claim Rejections - 35 USC § 112, First Paragraph
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, 6-9, 11, 13-14 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 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, 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.
Scope of the claims
Claims 1, 6-9, 11, 13-14 are directed to a peptide comprising one or more peptides defined by SEQ ID Nos:1-8 (defined amino acid sequences) or SEQ ID Nos:9-12 (which are variable sequences with many potential sequences encompassed SEQ ID Nos:9-12, HD1; HD6/7, HD2, HD8 derivatives). SEQ ID NO:9 (HD1 derivative) encompasses peptides having multiple variable amino acid positions, thereby defining a genus of structurally distinct peptide sequences.
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed.
Accordingly, the scope of the claims encompasses all peptides falling within SEQ ID Nos1-8, HD1, DH6/7, HD2 and HD8 derivative, including HD1 derivative which is the most broad, in addition to additional conservative substitutions that satisfy the selective binding function, including peptides not expressly exemplified in the specification.
Actual Reduction to Practice
MPEP § 2163 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. 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.
The specification demonstrates actual reduction to practice for specific peptide species, including HD1-HD8 (SEQ ID NOS:1-8) and certain individual substituted variants thereof (see claims 3-5). These peptides were identified, synthesized, and experimentally evaluated for binding to unbundled Huntington exon-1 fibrils using biochemical, biophysical, and cell based assays. However, the specification does not demonstrate actual reduction to practice for the full scope of peptides encompassed by SEQ ID Nos:9-12, including one or more conservative substitutions thereof (at multiple positions). Reduction to practice of a limited number of species does not establish possession of the entire claimed genus. The specification includes alanine scanning analyses of HD1 and HD8 (e.g. figures 12-13), which demonstrates that substitution of individual residues with alanine can substantially reduce or abolish binding to unbundled Huntingtin exon-1 fibrils. These results confirm that the claimed selective binding function is highly dependent on precise amino acid identity and position. However, the alanine scanning data do not establish a general structure function relationship applicable across the full scope of peptides encompassed by SEQ IDNOs:9-12 and variants thereof. Rather, the data show the unpredictability of binding outcome upon sequence modification and fail to identify common structural features or substitution rules that would enable a person of ordinary skill in the art to recognize which peptides within the claimed genus (which is inclusive to further variants due to claim 2) would have the selective binding.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 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, 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 thereof.
While the specification discloses certain conservative substitutions for specific peptides (e.g. SEQ ID NO1 and 8 variants), it does not provide objective structural criteria defining which conservative substitutions within SEQ ID Nos:9-12 preserves selective binding. The disclosure does not identify which amino acid positions tolerate substitution across the full genus, nor does it define limits on the number or combination of conservative substitutions that maintain the claimed binding function. The term “conservative amino acid substitution”, is itself structurally broad and encompasses numerous amino acid replacements with differing physicochemical properties. The specification does not describe sufficient characteristics to distinguish peptides within the variants encompassed by instant claim 1 that selectively bind unbounded fibrils from those that do not.
Physical/Chemical Properties
The specification describes physical and chemical properties (peptide length, synthesis, labeling and multimerization) for specific exemplified peptides and selected variants. However, the specification does not establish that peptides across the full scope of derivatives claimed with conservative substitutions share common physical or chemical properties that correlate with selective binding to unbundled Huntington exon-1 fibrils.
The specification further illustrates the lack of sufficient identifying characteristics for the claimed genus through comparison with the previously reported peptide QBP1. As described in paragraphs [0139]–[0140] and FIG. 7, QBP1 binds unbundled Huntingtin fibrils above background levels, yet exhibits greater than ten-fold lower binding relative to HD1 and HD8. Thus, the specification acknowledges the existence of peptides that bind unbundled Huntingtin fibrils, but do not exhibit the degree of selective binding demonstrated by HD1 and HD8.
The claims, however, encompass derivatives as defined by (ix)-(xiii) that selectively bind unbundled Huntingtin exon-1 fibrils, without providing structural criteria distinguishing peptides that exhibit HD1/HD8-like selectivity from peptides that behave more like QBP1. The disclosure does not identify common structural features, sequence motifs, or substitution patterns of the derivatives that correlate with the claimed selective binding, nor does it provide guidance sufficient to allow a person of ordinary skill in the art to recognize which peptides within the claimed scope would satisfy the functional limitation.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification demonstrates that certain specific peptides selectively bind unbundled Huntingtin exon-1 fibrils. The disclosure further shows that some substitutions diminish or abolish binding, indicating that binding is highly sequence-dependent. However, the specification does not disclose a predictive structure–function relationship that would allow a person of ordinary skill in the art to determine which peptides within the derivatives described in instant claim 1 will retain the claimed selective binding. Functional language alone does not establish written description of a structurally diverse genus absent disclosure of common structural features correlating structure with function.
The comparison to QBP1 further demonstrates that binding to unbundled Huntingtin fibrils alone is insufficient to define the claimed genus. The specification expressly distinguishes HD1 and HD8 from QBP1 based on the magnitude of binding and selectivity, indicating that selective binding is a quantitative and sequence-dependent property. However, the specification does not disclose a predictive structure–function relationship explaining why sequences encompassed by the instant claims exhibit HD1/HD8-like selectivity while other peptides, including known binders such as QBP1, do not.
In the absence of such disclosed correlation, the specification fails to demonstrate possession of peptides within the derivatives that exhibit the claimed selective binding across the full scope of the genus. Functional characterization of a limited number of peptides does not establish written description for a structurally diverse class where binding behavior varies significantly among members.
Method of Making
The specification discloses general methods for synthesizing, modifying, and testing peptides. While these methods enable the making and evaluation of peptides, the ability to synthesize and screen peptides does not demonstrate possession of the full scope of the claimed genus.
Conclusion
The specification demonstrates possession of specific peptide species and certain individual conservative substitutions thereof. However, the claims encompass a broad genus of peptide derivatives defined by the sequences in instant claim 1 (ix)-(xiii) and further expanded by conservative amino acid substitutions, without sufficient disclosure of representative species or common structural features correlating structure with the claimed selective binding function across the full scope.
Accordingly, the specification does not reasonably convey to a person of ordinary skill in the art that the inventors were in possession of the full scope of the claimed invention at the time of filing, and Claims 1, 6-9, 11, 13-14 therefore fail to satisfy the written description requirement of 35 U.S.C. §112(a).
Response to Applicant’s Arguments
Applicants argue “On pages 4-9 of the Action, claims 1, 2, 6-9, 11, 13, 14, and 28 are rejected under 35 U.S.C. §112, first paragraph as allegedly failing to comply with the written description requirement. Applicant has revised the claims to be consistent with the drawings and to recite specifically defined sequences, which no longer include within their literal scope conservative amino acid substitutions. In view of the reasonable number of species disclosed by the specification, applicant respectfully submits that the claimed genus, which is not as broad as the Action contends, is adequately supported by the specification. Accordingly, applicant requests that the Examiner reconsider and withdraw this rejection.”
Applicant’s argument has been fully considered but not found persuasive. Although Applicant amended the claims to remove conservative substitutions language, claim 1 continues to encompass broad peptide genera defined by SEQ ID Nos:9-12 (HD1, HD6/7, HD2 and HD8 derivatives). For example HD1 derivative (SEQ ID NO:9) contains numerous independently variable amino acid positions and encompasses a very large number of distinct peptide species. The specification discloses only a limited subset of species within these genera and does not identify structural features common to the full scope of the claimed peptides that correlate with the asserted binding activity. Accordingly, the amendment does not overcome the written description rejection because the specification still fails to reasonably convey possession of the full scope of the peptide genera recited in the claims.
Claim Rejections - 35 USC § 112
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 13 remains 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 13 recites peptide constructs comprising combinations of SEQ ID Nos, including constructs comprising SEQ ID NO:35. However, the identity of SEQ ID NO:35 is not reasonably certain. Specifically, Figure 17 depicts SEQ ID NO:35 as the amino acid sequence GSGTSGSS, whereas the sequence listing identifies SEQ ID NO:35 as MDWWAMWPSL. Because claim 13 relies upon SEQ ID NO:35 to define the structure of the claimed peptide constructs, and because the disclosure provides conflicting amino acid sequences for SEQ ID NO:35, one of ordinary skill in the art would not be able to determine with reasonable certainty the structure and scope of the claimed constructs. Accordingly the metes and bounds of claim 13 are unclear.
Response to Applicant’s Arguments
Applicants have not addressed the fact that it is unclear what sequence is encompassed by instant SEQ ID NO:35. Specifically, Figure 17 depicts SEQ ID NO:35 as the amino acid sequence GSGTSGSS, whereas the sequence listing identifies SEQ ID NO:35 as MDWWAMWPSL. Because claim 13 relies upon SEQ ID NO:35 to define the structure of the claimed peptide constructs, and because the disclosure provides conflicting amino acid sequences for SEQ ID NO:35, one of ordinary skill in the art would not be able to determine with reasonable certainty the structure and scope of the claimed constructs. Accordingly the metes and bounds of claim 13 are unclear.
New Rejections
Claim Rejections - 35 USC § 112
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, 6-9, 11, 13-14 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 1 recites “a peptide comprising one or more peptides that selectively bind to unbundled fibrils of Huntingtin exon 1, wherein each of said one or more peptides has a length of 10 amino acids or less and consists of one or more sequences selected from the group consisting of SEQ ID Nos:1-8 and derivative sequences (ix)-(xiii). The scope of the claim is unclear for several reasons. First, claim 1 requires that each peptide have a length of “10 amino acids or less”, while simultaneously reciting that each peptide consists of “one or more sequences” selected from the recited group. However, each of SEQ ID Nos:1-8 and the derivative sequences recited in limitations (ix)-(xiii) appears to be a 10 amino acid sequence. Accordingly, it is unclear how a peptide may consist of “one or more sequences” selected form the recited group while still having a length of “10 amino acids or less”. A peptide containing more than one recited sequence would appear to exceed the claimed length limitation, whereas a peptide containing only one sequence renders the phrase “one or more sequences” unclear as to its intended scope.
Second, claim 1 recites that each peptide has a length of “10 amino acids or less”, yet all expressly recited sequences and derivative sequences appear to contain 10 amino acids. Therefore, the claim does not reasonably inform one of ordinary skill in the art what peptides having fewer than 10 amino acids are encompassed by the claim.
Furthermore, claim 1 employs the transitional phrase “comprising” with respect to the claimed peptide while simultaneously requiring that “each of said one or more peptides” “consist of” one or more recited sequences. As claimed, it is unclear whether the claimed peptide is itself a single peptide molecule, a collection of peptide molecules, or a larger peptide construct containing the recited peptides. The claim therefore fails to clearly define the structural relationship between the claimed peptide and the recited “one or more peptides”. Consequently, one of ordinary skill in the art would not be able to determine with reasonable certainty whether additional amino acid residues, linked peptide constructs, fusion peptides, or covalently connected peptide species are within the scope of the claim.
Further, dependent claims 6-9. 11 and 13 recite embodiments in which multiple peptides are covalently linked to one another and/or connected by one or more linkers. In view of claim 1’s requirement that each peptide having a length of 10 amino acids or less and consist of the recited sequences, it is unclear how such linked peptide constructs satisfy the limitation of claim 1 and whether such embodiments fall within the scope of the independent claim. Accordingly, the metes and bounds of claim 1 cannot be determined with reasonable certainty. Claims 6-9, 11, 13-14 are also rejected due to their dependence on claim 1 and not further clarifying these points of confusion.
Claim 11 is indefinite because it is unclear what is encompassed by “at least two of the peptides connected by the one or more linkers”. The claim fails to clearly identify which peptides are being connected, whether the peptides must be different or may be identical, and the structural relationship required between the peptides and the linker(s). Accordingly, the metes and bounds of the claim cannot be determined with reasonable certainty.
Conclusion
No claims are allowed.
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 ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654
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