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
Status of Application, Amendments, and/or Claims
Applicant's amendment filed on 07/17/2026 has been entered. Claims 5-21 are canceled. New claims 22-38 pending. Claims 1 and 22-38 are pending. Claims 1 and 22-37 are currently under consideration. Claim 38 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Withdrawn Objections and/or Rejections
The rejection of claim 1 under 35 U.S.C. 112(a) is withdrawn in view of amended claim.
Claim Rejections under 35 USC § 102 (a)(1)
(i). The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(ii). Claims 1 and 24-37 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Gordon et al. (Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL. Blood 113 (18): 4381-4390, April 30, 2009).
Gordon et al. teach a mutant human Notch NRR (Negative Regulatory Region) comprising H1545P, leading to ligand-independent increases in signaling in reporter gene assays (see, e.g., Abstract). Gordon et al. teach a mutant Notch NRR comprising a single point mutation: L1575P, L1594P, L1601P, V1677D, L1679P, 11681N, A1702P (page 4382, the 3rd paragraph of left column; Fig. 1; Table 2 on page 4387). Such a mutant Notch NRR would inherently induce ligand-independent activation of regulated intramembrane proteolysis resulting in Notch signaling or SynNotch signaling. Gordon et al. further teach recombinant expression and purification of NRR from human Notch1 using a pET 15b vector (page 4382, left column, the 3rd paragraph). It is noted that claim 1, in part (i) and part (iii), recites “wherein the mutant Notch NRR is comprised in a fusion protein, and wherein the fusion protein further comprises a Notch NRR-binding antibody”. However, since claim 1 is drawn to a synthetic nucleic acid encoding a mutant Notch NRR, not a fusion protein comprising a mutant Notch NRR and a Notch NRR-binding antibody, such a recitation does not limit the claimed subject matter. Thus, the teaching of Gordon et al. meets the limitations of claim 1 (i) and (iii) and 24-37
(iii). Response to Applicant’s argument
Applicant argues that Gordon et al. neither teach nor suggest a fusion protein comprising a mutant Notch NRR having the amino acid sequence of SEQ ID NOS: 1 or 3 and a Notch NRR-binding antibody.
Applicant’s argument has been fully considered but is not deemed to be persuasive. First, as noted in the rejection above, claim 1, in part (i) and part (iii), recites “wherein the mutant Notch NRR is comprised in a fusion protein, and wherein the fusion protein further comprises a Notch NRR-binding antibody”. However, since claim 1 is drawn to a synthetic nucleic acid encoding a mutant Notch NRR, not a fusion protein comprising a mutant Notch NRR and a Notch NRR-binding antibody, such a recitation does not limit the claimed subject matter. Thus, the teaching of Gordon et al. meets the limitations of claim 1 (i) and (iii).
Second, Gordon et al. teach a mutant human Notch NRR (Negative Regulatory Region) comprising V1677D (see the rejection above). The wide type of human NRR1 would comprise the amino acid sequence of SEQ ID NO: 3, whereas the mutant human Notch NRR comprising V1677D would comprise the amino acid sequence of SEQ ID NO: 1.
Claim Rejections Under 35 USC § 112 (d)
(i). 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.
(ii). Claims 24-37 are rejected under 35 U.S.C. 112 (d), 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.
Specifically, claim 24 recites a limitation, “wherein the mutant Notch NRR is comprised in a fusion protein, and wherein the fusion protein further comprises a Notch NRR-binding antibody”. However, such a limitation is already present in claim 1, from which claim 24 depends. Claims 25-37 are rejected as dependent claims from claim 24
Claim Objection
Claims 22-23 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The Pertinent Prior Art
The following prior art is considered to be relevant to the instantly claimed subject matter, but not relied on in the art rejection:
(i). US 2008/0241150 A1 (Pub. Date: Oct. 2, 2008) teaches a human Notch1 mutant comprising L1594P, V1677D, L1679P, L1681N, or A1702P (page 6, paragraph [0058]).
(ii). US 2009/0081238 A1 teaches a human Notch1 mutant comprising L1594P, V1677D, L1679P, L1681N, or A1702P (page 21, paragraphs [0202]-[0203]).
(iii). US 2007/0077245 A1 (Pub. Date: Apr. 5, 2007) teaches a human Notch1 mutant comprising V1677D, L1679P, L1681N, or A1702P (page 10, paragraph [0111]).
(iv). Weng et al. (Science 306, 269-271, 2004) teach a human Notch1 mutant comprising L1575P, L1594P, or L1601P (see, e.g., Fig. 4).
Conclusion
No claims are allowed.
Advisory Information
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 extension fee 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 Ruixiang Li whose telephone number is (571) 272-0875. The examiner can normally be reached on Monday through Friday from 8:30 am to 5:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached on (571) 272-0857. The fax number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/RUIXIANG LI/Primary Examiner, Art Unit 1674 July 29, 2026
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