DETAILED ACTION
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 .
Status of Application, Amendments and/or Claims
1. Claim 1 has been amended and new claim 34 has been added as requested in the amendment filed January 20, 2026. Following the amendment, claims 1, 6-7, 9, 15-16, 20-22, 27 and 29-34 are pending in the present application.
2. Claims 21-22, 27 and 27-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 June 29, 2022.
3. Claims 1, 6-7, 9, 15-16, 20 and 34 are under examination in the current office action.
Information Disclosure Statement
4. The information disclosure statement (IDS) filed 01/20/2026 has been considered and the references therein are of record.
Withdrawn Claim Rejections
5. The rejection of claims 1, 9, 16 and 20 under 35 U.S.C. 102(a)(1) as being anticipated by Lindquist et al. (WO 02/065136), as discussed at sections 5-7 of the 10/20/2025 office action (OA), is withdrawn in view of applicant’s amendments to the claims. In particular, Lindquist does not teach an engineered mutant huntingtin protein (mHTT) that comprises a fragment of exon 1 of HTT lacking amino acid residues 2-16 of exon 1 of HTT as now required by the claims.
6. The rejection of claim 15 under 35 U.S.C. 103 as being unpatentable over Lindquist et al. in view of Hasholt et al. (2003) (see sections 8-10 of the 10/20/2025 OA), is withdrawn in view of applicant’s amendments to the claims. Neither Lindquist nor Hasholt teach or suggest an engineered mutant huntingtin protein (mHTT) that comprises a fragment of exon 1 of HTT lacking amino acid residues 2-16 of exon 1 of HTT as now required by the claims.
7. The rejection of claims 6-7 under 35 U.S.C. 103 as being unpatentable over Lindquist et al. (set forth at section 11 of the 10/20/2025 OA), is withdrawn in view of applicant’s amendments to the claims. Lindquist does not teach or suggest an engineered mutant huntingtin protein (mHTT) that comprises a fragment of exon 1 of HTT lacking amino acid residues 2-16 of exon 1 of HTT as now required by the claims.
New Claim Rejections, Necessitated by Amendment
Claim Rejections - 35 USC § 103
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, 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.
8. Claim(s) 1, 6-7, 9, 16, 20 and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gu et al. (Neuron, 2015, 85:726-741, including Supplemental Information, 31 pages; of record) in view of Lindquist et al. (WO 02/065136; of record).
Gu et al. teach a nucleic acid molecule encoding for an engineered human mutant huntingtin protein (mHTT) comprising a polyQ region containing 97, 72 or wild type (WT) 31 consecutive glutamine (Q) residues and having a deletion of residues 2-16 in the N17 domain of exon 1 of HTT (DN17-mHTT-97Q, DN17-mHTT-72Q, and DN17-HTT-31Q, respectively) (see paragraph spanning cols. 1-2 and col.2 at p. 727, Fig. 1, and description for Suppl Fig. S1 at p. 4 of Suppl Info), which is on point to certain limitations of claim 1 (a nucleic acid molecule comprising a nucleotide sequence encoding a protein comprising an engineered huntingtin protein (mHTT), mHTT comprises a fragment of exon 1 of HTT comprising a polyQ region…and further lacking amino acid residues 2 through 16 of exon 1 of HTT).
Gu teaches the construction of plasmids containing mutant DN17 forms of exon 1 HTT operably linked to enhanced green fluorescent protein (EGFP) (DN17-mHTT-72Q-EGFP) and expression as a fusion protein in transiently transfected HEK293 cells, which are isolated mammalian cells (Suppl Fig. S1 at p. 3 and figure description at p. 4 of Suppl Info). Thus, Gu teaches the required elements of claim 7 (the nucleotide sequence encoding the mHTT further comprises a nucleotide sequence encoding a detectable marker), claim 9 (a cell comprising a nucleic acid molecule of claim 1), claim 15 (a mammalian cell), claim 16 (a fusion protein comprising a detectable protein), and claim 20 (the cell is an isolated cell).
However, Gu does not teach that nucleic acid molecule encodes for an engineered mHTT protein comprising a polyQ region consisting of 46 glutamine residues as in claim 1, or that the nucleotide sequence comprises SEQ ID NO: 3 as in claim 6, or that nucleotide sequence encodes an amino acid sequence comprising SEQ ID NO: 4 as in claim 34.
Consistent with the teachings of Gu, Lindquist et al. disclose a mutant huntingtin polypeptide and encoding nucleic acids sequences thereof, which comprise an N-terminal region of exon 1 of HTT and a polyglutamine (pQ) repeat region (p. 4 lines 13-32). Lindquist teaches that the mHTT polypeptide may have between 10 and 150 pQ repeats, and specifically 46 pQ repeats (p. 44 lines 28-31). An mHTT polypeptide containing 47 pQ repeats (HtQ47), for example, is contemplated at p. 4 lines 23-25 and p. 18 line 9, which is noted to be a potentially toxic fibril-forming protein. Lindquist discloses that this polypeptide may be a fusion protein comprising the mHTT and a reporter polypeptide, such as GFP (p. 5 lines 1-6; Example 2 at p. 60).
The amino acid sequence of instant SEQ ID NO: 4 is that of a fusion protein comprising an N-terminal region of HTT comprising a deletion of residues 2-16 (DN17) of exon 1 of HTT and 46 glutamine residues linked to green fluorescent protein (GFP), and instant SEQ ID NO: 3 is the nucleotide sequence that encodes for SEQ ID NO: 4.
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the DN17-mHTT-GFP nucleic acid molecule of Gu containing 97 or 72 consecutive polyglutamine residues to instead contain 46 pQ repeats as taught by Lindquist and thereby arrive at the presently claimed invention. In doing so, the nucleic acid sequence of the resultant polynucleotide, DN17-mHTT-46Q-GFP, would be that of the instant SEQ ID NO: 3, and would encode for the fusion protein of instant SEQ ID NO: 4 as claimed. Given the teachings of Lindquist, the skilled artisan would have been able to at once envisage an mHTT containing any number of pQ repeats between 10 and 150, and specifically 46 pQ repeats, and Lindquist also teaches that an mHTT-47Q polypeptide is mildly toxic to cells made to express the protein. And given the teachings of Gu, the artisan would have recognized that the deletion of residues 2-16 in the N-terminus of exon 1 of HTT (DN17-mHTT) causes the resultant mHTT fragments to collect in the nucleus of cells, dramatically accelerating mHTT pathology (see abstract). Thus, a DN17-mHTT-46Q-GFP construct would have been obvious as it combines a known pathogenesis-inducing mutation (DN17) with a mutation (46Q) causing mild toxicity, which would be beneficial for studying disease pathology related to Huntington’s disease (HD) as well as for screening for candidate agents (see pp. 48-49 of Linquist). This is particularly true when expressed in a transgenic mouse model of HD, as described in Gu. This is also because the artisan has good reason to pursue the known options within his or her technical grasp to obtain predictable results. Such would amount to the simple substitution of one known element for another (i.e., 46Q for 72Q or 91Q) to obtain predictable results.
Conclusion
9. No claims are allowed.
10. 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.
Advisory Information
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/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675