DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Amendment after Non-final office action filed on 9/25/2026 is acknowledged.
3. Claim filed on 9/25/2026 is acknowledged.
4. Claims 10 and 11 have been cancelled.
5. New claims 23 and 24 have been added.
6. Claims 1-9 and 12-24 are pending in this application.
7. Claims 4-6, 8, 9, 12-15, 17 and 19-22 remain withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Claims 3, 7, 16, 18, 23 and 24 remain/are withdrawn from consideration as being drawn to non-elected species.
8. Applicant elected without traverse of Group 1 (claims 1-3, 7, 16 and 18) and elected without traverse of SEQ ID NO: 64 as species of polypeptide in the reply filed on 2/20/2026.
Restriction requirement was deemed proper and made FINAL in the previous office action. Group 1 is drawn to a polypeptide comprising an engineered zinc finger peptide having from 8 to 18 zinc finger domains (F1 to F18) according to Formula 2: X0-2 C X1-5 C X2-7 X-1 X+1 X+2 X+3 X+4 X+5 X+6 H X3-6 H/c where X is any amino acid, numbers in subscript indicate a number of residues represented by X, and numbers in superscript indicate a position of the amino acid in the α-helix; wherein H/c indicates the amino acid at the C-terminus of Formula 2 is C or H; wherein the sequence X-1X+1X+2X+3X+4X+5X+6 in at least 8 adjacent zinc finger domains in the engineered zinc finger peptide is selected from the followings patterns (A)-(D), and wherein the polypeptide binds to a 5'-GCG-3' nucleic acid repeat sequence. A search was conducted on the elected species; and this appears to be free of prior art. A search was extended to the genus in claim 1; and prior art was found. Claims 3, 7, 16, 18, 23 and 24 remain/are withdrawn from consideration as being drawn to non-elected species. Claims 1 and 2 are examined on the merits in this office action.
Withdrawn Objections and Rejections
9. Objection to the specification is hereby withdrawn in view of Applicant’s amendment to the specification.
10. Objection to the drawings is hereby withdrawn in view of Applicant’s amendment to the drawings.
11. Rejection to claims 1 and 2 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is hereby withdrawn in view of Applicant’s amendment to the claim.
12. Rejection to claims 1 and 2 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph (written description) is hereby withdrawn in view of Applicant’s amendment to the claim.
Maintained/Revised Objections
13. (Revised due to Applicant’s amendment to the claim) Claim 1 remains objected to for the following minor informality: Applicant is suggested to amend claim 1 as: “An engineered zinc finger peptide comprising multiple zinc finger domains according to Formula 2: X0-2CX1-5CX2-7X-1X+1X+2X+3X+4X+5X+6HX3-6H/c, wherein: X is any amino acid; the numbers in subscript indicate number of residues represented by X, and the numbers in superscript indicate position of the amino acid in α-helix; H/c indicates the amino acid at the C-terminus of Formula 2 is C or H; wherein the number of zinc finger domains in the engineered zinc finger peptide is from 8 to 18, and the zinc finger domains are indicated as F1 to F18; wherein the sequence…patterns (A)-(D):
F1
F2, F4, F6, F8, F10, F12, F14, F16, F18
F3, F5, F7, F9, F11, F13, F15, F17
(A)
SEQ ID NO: 4
SEQ ID NO: 4
SEQ ID NO: 4
(B)
SEQ ID NO: 5
SEQ ID NO: 5
SEQ ID NO: 5
(C)
SEQ ID NO: 4
SEQ ID NO: 4
SEQ ID NO: 5
(D)
SEQ ID NO: 4
SEQ ID NO: 5
SEQ ID NO: 4
; and wherein the engineered zinc finger peptide binds to a 5'-GCG-3' nucleic acid repeat sequence“.
14. (Revised due to Applicant’s amendment to the claim) Claim 2 remains objected to for the following minor informality: Applicant is suggested to amend claim 2 as “The engineered zinc finger peptide according to claim 1, wherein: (i) the number of the zinc finger domain is 10, 11, 12 or 18; or (ii) all of the zinc finger domains in the engineered zinc finger peptide are defined according to the pattern of (A), (B), (C) or (D)”. In the instant case, part (ii) recited in instant claim 2 is a species of part (i).
Response to Applicant's Arguments
15. Applicant either fails to address all the minor issues in these claims, or Applicant’s amendment to the claim introduces additional minor issues into these claims. Therefore, these objections are deemed proper and are hereby maintained.
Maintained/Revised Rejections
Claim Rejections - 35 U.S.C. § 103
16. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
17. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
18. (Revised due to Applicant’s amendment to the claim) Claims 1 and 2 remain rejected under 35 U.S.C. 103 as being unpatentable over Müller et al (Muscle Nerve, 2001, 24, pages 120-122, cited and enclosed in the previous office action) in view of Desjarlais et al (Proc Natl Acad Sci U S A, 1993, 90, pages 2256-2260, cited and enclosed in the previous office action), Eisenberg et al (US 2003/0092000 A1, cited and enclosed in the previous office action) and Garriga-Canut et al (PNAS, 21012, pages E3136-E3145, filed with IDS).
The instant claims 1 and 2 drawn to are a polypeptide comprising an engineered zinc finger peptide having from 8 to 18 zinc finger domains (F1 to F18) according to Formula 2: X0-2 C X1-5 C X2-7 X-1 X+1 X+2 X+3 X+4 X+5 X+6 H X3-6 H/c where X is any amino acid, numbers in subscript indicate a number of residues represented by X, and numbers in superscript indicate a position of the amino acid in the α-helix; wherein H/c indicates the amino acid at the C-terminus of Formula 2 is C or H; wherein the sequence X-1X+1X+2X+3X+4X+5X+6 in at least 8 adjacent zinc finger domains in the engineered zinc finger peptide is selected from the followings patterns (A)-(D), and wherein the polypeptide binds to a 5'-GCG-3' nucleic acid repeat sequence.
Müller et al, throughout the literature, teach short GCG repeat expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy (OPMD) in French-Canadian and Italian pedigrees; and patients with OPMD contain GCG repeats of (GCG)8-13, for example, Title; Abstract; and the 1st paragraph in Section “RESULTS”.
The difference between the reference and instant claims 1 and 2 is that the reference does not teach the polypeptide recited in instant claims 1 and 2.
However, Desjarlais et al, throughout the literature, teach a designed zinc-finger protein comprising three zinc fingers with the amino acid sequence CPECGKSFS RSDELQRHQRTH binds to the sequence 5'-GCG-GCG-GCG-3', wherein the binding/recognition sequence is RSDELQR, for example, Abstract; and page 2257, Figure 1A. Desjarlais et al further teach such designed zinc-finger protein as a powerful vehicle for the production of desired site-specific DNA binding proteins, for example, Abstract; and page 2260, Section “Conclusions”.
Furthermore, Eisenberg et al teach that similar to the binding/recognition sequence RSDELQR in Desjarlais et al, RSDELTR or RSDERKR is binding/recognition sequence for -GCG-, for example, pages 20-21, paragraphs [0206-[0208]. The binding/recognition sequence RSDELTR or RSDERKR in Eisenberg et al meets the limitations of instant SEQ ID NO: 4 or 5. Therefore, in view of the combined teachings of Desjarlais et al and Eisenberg et al, it would have been obvious to one of ordinary skilled in the art to develop a designed zinc-finger protein comprising three zinc fingers with the amino acid sequence CPECGKSFSRSDELTRHQRTH or CPECGKSFS RSDERKRHQRTH, wherein the designed zinc-finger protein binds to the sequence 5'-GCG-GCG-GCG-3'. The designed zinc-finger protein developed from the combined teachings of Desjarlais et al and Eisenberg et al is a simple substitution of one known element for another to obtain predictable results (see MPEP § 2143 I).
In addition, Garriga-Canut et al, throughout the literature, teach Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by expanded CAG repeats in the huntingtin (HTT) gene; and synthetic zinc finger proteins (ZFPs) comprising multiple zinc finger peptides having binding/recognition sequence that binds to CAG repeats in the huntingtin (HTT) gene, wherein such synthetic zinc finger proteins can be used for optimizing longer-term therapeutic benefit for treating HD, for example, Abstract; and page E3143, left column, the 2nd paragraph. Garriga-Canut et al further teach using long artificial ZFP chains to bind longer CAG repeats more strongly than shorter repeats, including various synthetic zinc finger proteins with 4, 6, 11 or 18 binding/recognition sequence for binding to (CAG)5, (CAG)7, and/or (CAG)13, for example, Abstract; and Figures 1-3.
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Müller et al, Desjarlais et al, Eisenberg et al and Garriga-Canut et al to develop a designed zinc-finger protein comprising at least 8, such as 11 or 18, zinc fingers with the amino acid sequence CPECGKSFSRSDELTRHQRTH (instant pattern (A)) or CPECGKSFSRSDERKRHQRTH (instant pattern (B)), wherein the designed zinc-finger protein binds to the longer 5'-GCG-3' repeat sequence in patients with OPMD and can be used to treat OPMD.
One of ordinary skilled in the art would have been motivated to combine the teachings of Müller et al, Desjarlais et al, Eisenberg et al and Garriga-Canut et al to develop a designed zinc-finger protein comprising at least 8, such as 11 or 18, zinc fingers with the amino acid sequence CPECGKSFSRSDELTRHQRTH (instant pattern (A)) or CPECGKSFSRSDERKRHQRTH (instant pattern (B)), wherein the designed zinc-finger protein binds to the longer 5'-GCG-3' repeat sequence in patients with OPMD and can be used to treat OPMD, because Desjarlais et al, throughout the literature, teach a designed zinc-finger protein comprising three zinc fingers with the amino acid sequence CPECGKSFS RSDELQRHQRTH binds to the sequence 5'-GCG-GCG-GCG-3', wherein the binding/recognition sequence is RSDELQR. Desjarlais et al further teach such designed zinc-finger protein as a powerful vehicle for the production of desired site-specific DNA binding proteins. Eisenberg et al teach that similar to the binding/recognition sequence RSDELQR in Desjarlais et al, RSDELTR or RSDERKR is binding/recognition sequence for -GCG-. Therefore, in view of the combined teachings of Desjarlais et al and Eisenberg et al, it would have been obvious to one of ordinary skilled in the art to develop a designed zinc-finger protein comprising three zinc fingers with the amino acid sequence CPECGKSFSRSDELTRHQRTH or CPECGKSFS RSDERKRHQRTH, wherein the designed zinc-finger protein binds to the sequence 5'-GCG-GCG-GCG-3'. The designed zinc-finger protein developed from the combined teachings of Desjarlais et al and Eisenberg et al is a simple substitution of one known element for another to obtain predictable results (see MPEP § 2143 I). Garriga-Canut et al, throughout the literature, teach Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by expanded CAG repeats in the huntingtin (HTT) gene; and synthetic zinc finger proteins (ZFPs) comprising multiple zinc finger peptides having binding/recognition sequence that binds to CAG repeats in the huntingtin (HTT) gene, wherein such synthetic zinc finger proteins can be used for optimizing longer-term therapeutic benefit for treating HD. Garriga-Canut et al further teach using long artificial ZFP chains to bind longer CAG repeats more strongly than shorter repeats, including various synthetic zinc finger proteins with 4, 6, 11 or 18 binding/recognition sequence for binding to (CAG)5, (CAG)7, and/or (CAG)13.
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Müller et al, Desjarlais et al, Eisenberg et al and Garriga-Canut et al to develop a designed zinc-finger protein comprising at least 8, such as 11 or 18, zinc fingers with the amino acid sequence CPECGKSFSRSDELTRHQRTH (instant pattern (A)) or CPECGKSFSRSDERKRHQRTH (instant pattern (B)), wherein the designed zinc-finger protein binds to the longer 5'-GCG-3' repeat sequence in patients with OPMD and can be used to treat OPMD.
Response to Applicant's Arguments
19. Applicant argues that “the Office has failed to establish a motivation to combine or modify the references in the manner alleged in the Office Action.”; and “A conclusion of obviousness cannot derive from the applicant's specification.” by arguing about each of the cited prior art references individually.
20. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant's arguments about instant rejection, the Examiner agrees that none of the cited references individually teaches or suggests the polypeptide recited in instant claims 1 and 2; and none of the cited references anticipates the polypeptide recited in instant claims 1 and 2. However, the Examiner would like to point out that instant claims 1 and 2 are rejected under 35 U.S.C. 103 (obviousness type), and the rejection is based on the combined teachings of Müller et al, Desjarlais et al, Eisenberg et al and Garriga-Canut et al, it is not necessary for each of the cited references to teach all the limitations of instant claims. Furthermore, the Examiner would like to point out that the MPEP states "One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references…" (see MPEP § 2145 IV).
In response to Applicant's arguments that “the Office has failed to establish a motivation to combine or modify the references in the manner alleged in the Office Action.”, as stated in Section 18 above, in the instant case, Müller et al, throughout the literature, teach short GCG repeat expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy (OPMD) in French-Canadian and Italian pedigrees; and patients with OPMD contain GCG repeats of (GCG)8-13. Furthermore, in view of the combined teachings of Desjarlais et al and Eisenberg et al, it would have been obvious to one of ordinary skilled in the art to develop a designed zinc-finger protein comprising three zinc fingers with the amino acid sequence CPECGKSFSRSDELTRHQRTH or CPECGKSFS RSDERKRHQRTH, wherein the designed zinc-finger protein binds to the sequence 5'-GCG-GCG-GCG-3'. The designed zinc-finger protein developed from the combined teachings of Desjarlais et al and Eisenberg et al is a simple substitution of one known element for another to obtain predictable results (see MPEP § 2143 I). In addition, Garriga-Canut et al, throughout the literature, teach Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by expanded CAG repeats in the huntingtin (HTT) gene; and synthetic zinc finger proteins (ZFPs) comprising multiple zinc finger peptides having binding/recognition sequence that binds to CAG repeats in the huntingtin (HTT) gene, wherein such synthetic zinc finger proteins can be used for optimizing longer-term therapeutic benefit for treating HD. Garriga-Canut et al further teach using long artificial ZFP chains to bind longer CAG repeats more strongly than shorter repeats, including various synthetic zinc finger proteins with 4, 6, 11 or 18 binding/recognition sequence for binding to (CAG)5, (CAG)7, and/or (CAG)13. In the instant case, both OPMD taught in Müller et al and HD taught in Garriga-Canut et al are diseases caused by abnormal expansion of a nucleic acid repeat. Therefore, in view of the combined teachings of the cited prior art references as set forth in Section 18 above, one of ordinary skilled in the art would have been motivated to develop a designed zinc-finger protein comprising at least 8, such as 11 or 18, zinc fingers with the amino acid sequence CPECGKSFS RSDELTRHQRTH (instant pattern (A)) or CPECGKSFSRSDERKRHQRTH (instant pattern (B)), wherein the designed zinc-finger protein binds to the longer 5'-GCG-3' repeat sequence in patients with OPMD and can be used to treat OPMD.
In response to Applicant’s arguments that “A conclusion of obviousness cannot derive from the applicant's specification.” (impermissible hindsight), in the instant case, Applicant fails to point to any facet of instant rejection that is not found in the cited prior art references. It is unclear to the Examiner which part of the instant rejection is not based on the combined teachings of the cited references. Merely pointing out the differences between each of the cited references and instant claimed invention is not proof of hindsight reasoning. Furthermore, the MPEP states “"[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper." In re McLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971).” (see MPEP § 2145).
Taken all these together, the rejection is deemed proper and is hereby maintained.
Conclusion
THIS ACTION IS MADE FINAL. 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.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LI N KOMATSU whose telephone number is (571)270-3534. The examiner can normally be reached Mon-Fri 8am-4pm 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, Melissa Fisher can be reached on 5712707430. 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.
/LI N KOMATSU/Primary Examiner, Art Unit 1658
