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 .
Response to Amendment
The Amendment filed July 13, 2026, in response to the Non-final rejection of April 13, 2026 is acknowledged and has been entered.
Claims 1 and 42 were amended. Claims 2 and 8 were canceled. Claims 82-83 were added.
Claims 1, 3, 6, 10, 12, 14, 22-24, 32, 37, 42, 52-53, 56, 63, 66, 75-76, and 82-83 are currently under consideration.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Rejections Withdrawn
The rejection of claims 2, 8, and 42 under 35 U.S.C. 112(b) is withdrawn in view of applicants’ amendments.
The rejection of claim 2 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of applicants’ amendments.
The rejection of Claim(s) 1, 3, 6, 10, 12, 14, 22-24, 32, 37, 42, 52-53, 56, 63, 66, 75-76 and 82-83 under 35 U.S.C. 102(a)(1) as being anticipated by Emtage et al. WO-2019164979 (IDS, published 2019). (Paragraph citations use the PG-PUB 20200384030) as evidenced by UniProt, P07333, CSF1R_Human amino acid sequence, 1994) is withdrawn in view of applicants’ incorporation of non-rejected Claim 2 into the independent claim.
New Rejections Necessitated by Amendments
Claims 1, 3, 6, 10, 12, 14, 22-24, 32, 37, 42, 52-53, 56, 63, 66, 75, and 76 are rejected and new claims 82-83 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7, 11-12, 17, 24, 26, 34, 38, 42, 53, 56, 59-60, 67, 71 of copending Application No. 18551931(‘931) (reference application) for the reasons of record and for the reasons set forth below. Although the claims at issue are not identical, they are not patentably distinct from each other because amended claim 1 of the currently examined application is drawn to a chimeric polypeptide comprising, from N-terminus to C-terminus: a) an extracellular binding domain (ECD) having a binding affinity for a selected ligand; b) a linking sequence; c) a transmembrane domain (TMD) having at least about 80% sequence identity to the transmembrane domain of a Type 1 transmembrane receptor and comprising one or more ligand-inducible proteolytic cleavage sites; and d) an intracellular domain (ICD) comprising a transcriptional regulator, wherein binding of the selected ligand to the extracellular binding domain induces cleavage at the ligand- inducible proteolytic cleavage site between the transcriptional regulator and the linking sequence, and wherein the chimeric polypeptide does not comprise a sequence from a Notch receptor which contains overlapping subject matter with independent claim 1 of the ‘931 application drawn to: A chimeric receptor comprising, from N-terminus to C-terminus: a) an extracellular ligand-binding domain having a binding affinity for a selected ligand; b) a linking polypeptide; c) a transmembrane domain (TMD) comprising one or more ligand-inducible proteolytic cleavage sites; and d) an intracellular domain (ICD) comprising, in any order: (i) an intracellular signaling domain (SD) comprising at least one costimulatory domain derived from a signaling molecule and an activation domain, and (ii) a transcriptional regulator, and wherein binding of the selected ligand to the extracellular ligand-binding domain induces cleavage at [[a]]the one or more ligand-inducible proteolytic cleavage site disposed between the ICD and the linking polypeptide, wherein binding of the selected ligand to the extracellular ligand-binding domain induces proximal signaling cascades through the intracellular SD, and wherein the chimeric receptor does not comprise a LIN-12-Notch repeat (LNR) and/or a heterodimerization domain (HD) of a Notch receptor.
While the current application defines the transmembrane domain having at least about 80% sequence identity to a Type 1 Transmembrane receptor, the ‘931 application defines [0106] TMDs suitable for the chimeric receptors as any TMD of a type 1 transmembrane receptor including at least one γ-secretase cleavage site. These are inclusive of transmembrane domains from Type 1 transmembrane receptors IL1R1, IL1R2, IL6R, INSR, ERN1, ERN2, JAG2, KCNE1, KCNE2, KCNE3, KCNE4, KL, CHL1, PTPRF, SCN1B, SCN3B, NPR3, NGFR, PLXDC2, PAM, AGER, ROBO1, SORCS3, SORCS1, SORL1, SDC1, SDC2, SPN, TYR, TYRP1, DCT, VASN, FLT1, CDH5, PKHD1, NECTIN1, PCDHGC3, NRG1, LRP1B, CDH2, NRG2, PTPRK, SCN2B, Nradd, and PTPRM which would naturally include an amino acid sequence having at least 80% sequence identity to any one of SEQ ID NOS: 1-84, 178, 182-185, and 190-192 as set forth in claim 32 of the instant application.
Regarding claims 1 and 82-83 of the instant application, drawn to a heterologous STS- heterologous to the TMD and comprises a sequence having at least 90% sequence identity to a STS sequence from CSF1R, CXCL16, DAG1, GHR, PTPRF, AGER, KL, NRG1, LRP1B, Jag2, EPCAM, KCNE3, CDH2, NRG2, PTPRK, BTC, EPHA3, IL1R2, or PTPRM; claim 26 of the ‘931 application only requires that the STS be positioned between the TMD and ICD. But, the specification of the ‘931 application teaches [0109] that in some embodiments, the STS includes a sequence having at least 70% sequence identity, such as, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or 99% sequence identity to a STS sequence from Notch1, Notch2, Notch3, Notch4, CSF1R, CXCL16, DAG1, GHR, PTPRF, AGER, KL, NRG1, LRP1B, Jag2, EPCAM, KCNE3, CDH2, NRG2, PTPRK, BTC, EPHA3, IL1R2, or PTPRM. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim.
Regarding claim 6 of the instant application, the ‘931 specification teaches [0106] that NRG1 can be the TMD.
Claim 10 of the instant application is similar in scope to claim 2 and claim 11 of the ‘931 application.
Claim 12 and 14 of the instant application, is covered by claim 7 of the ‘931 application.
Claim 24 of the instant application defines nuclear localization sequences with transcriptional regulator sequences (e.g., Gal4-VP16, Gal4-VP64). These are species within the genus of the claimed transcriptional regulator of Claim 1 of the ‘931 application which are exemplified in [0116].
Recombinant nucleic acids, cells, and methods of use are overlapping between the two applications.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 6, 10, 12, 14, 22-24, 32, 37, 42, 52-53, 56, 63, 66, 75, 76, are rejected and new claims 82-83 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 14, 18-33, 45, 49, 53, 59-60, 70, 73, 82-83, 86, and 89 of copending Application No. 17/762687(‘687) (reference application) for the reasons of record and for the reasons set forth below.
Claims 1 and 45 of the ‘687 application are drawn to a chimeric polypeptide comprising, from N-terminus to C-terminus: a) an extracellular ligand binding domain (ECD) having a binding affinity for a selected ligand; b) a linking polypeptide comprising one, two, or three Robol fibronectin (Fn) repeats and a short sequence of from about two to about 20 amino acids; c) a transmembrane domain (TMD) comprising one or more ligand-inducible proteolytic cleavage sites; and d) an intracellular domain (ICD) comprising a transcription regulator, wherein binding of the selected ligand to the extracellular binding domain induces cleavage at the ligand-inducible proteolytic cleavage site between the transcription regulator and the linking polypeptide wherein (Claim 2) the recombinant nucleic acid chimeric polypeptide of claim 1 does not comprise a LIN-12-Notch repeat (LNR) and/or a heterodimerization domain (HD) of a Notch receptor.
The current claims are generic to any linking sequence (part b of claim 1) but the specification teaches [0086-0087] that the linking polypeptide can comprise one or multiple ROBO1 Fn repeats. Further, while the TMD of the ‘687 application is generic, the specification teaches [0078] that they can be any transmembrane domain of a Type 1 transmembrane receptor including at least one γ-secretase cleavage site.
Regarding claims 1 and 82-83 of the instant application, drawn to a heterologous STS- heterologous to the TMD and comprises a sequence having at least 90% sequence identity to a STS sequence from CSF1R, CXCL16, DAG1, GHR, PTPRF, AGER, KL, NRG1, LRP1B, Jag2, EPCAM, KCNE3, CDH2, NRG2, PTPRK, BTC, EPHA3, IL1R2, or PTPRM; claim 3 of the ‘687 application only requires that the STS be positioned between the TMD and ICD. But, the specification of the ‘687 application teaches [0082] that in some embodiments, the STS includes a sequence having at least 70% sequence identity, such as, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or 99% sequence identity to a STS sequence from Notch1, Notch2, Notch3, Notch4, CSF1R, CXCL16, DAG1, GHR, PTPRF, AGER, KL, NRG1, LRP1B, Jag2, EPCAM, KCNE3, CDH2, NRG2, PTPRK, BTC, EPHA3, IL1R2, or PTPRM. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim.
Regarding claim 6 of the instant application, the ‘687 specification teaches [0078] that NRG1 can be the TMD. Further, the ‘687 application defines [0078] TMDs suitable for the chimeric receptors as any TMD of a type 1 transmembrane receptor including at least one γ-secretase cleavage site. These are inclusive of transmembrane domains from Type 1 transmembrane receptors IL1R1, IL1R2, IL6R, INSR, ERN1, ERN2, JAG2, KCNE1, KCNE2, KCNE3, KCNE4, KL, CHL1, PTPRF, SCN1B, SCN3B, NPR3, NGFR, PLXDC2, PAM, AGER, ROBO1, SORCS3, SORCS1, SORL1, SDC1, SDC2, SPN, TYR, TYRP1, DCT, VASN, FLT1, CDH5, PKHD1, NECTIN1, PCDHGC3, NRG1, LRP1B, CDH2, NRG2, PTPRK, SCN2B, Nradd, and PTPRM which would naturally include an amino acid sequence having at least 80% sequence identity to any one of SEQ ID NOS: 1-84, 178, 182-185, and 190-192 as set forth in claim 32 of the instant application.
Claims 10 of the instant application is similar in scope to claim 24 of the ‘687 application.
Claims 23-24 of the instant application are similar in scope to claims 31-32 of the ‘687 application.
Recombinant nucleic acids, cells, cell cultures, and methods of use are overlapping between the two applications.
Claims 1, 3, 6, 10, 12, 14, 22-24, 32, 37, 42, 52-53, 56, 63, 66, 75, and 76 are rejected and new claims 82-83 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 8-10, 12, 13, 18-20, 24-25, 32, 36, 40, 51-52, 55, 62, 66, 75-76 of copending Application No. 17/762685(‘685) (reference application) for the reasons of record and for the reasons set forth below.
Claim 1 of the ‘685 application is drawn to a chimeric polypeptide comprising, from N-terminus to C-terminus: a) an extracellular ligand-binding domain having a binding affinity for a selected ligand; b) a linking polypeptide; c) a transmembrane domain comprising one or more ligand-inducible proteolytic cleavage sites; and d) an intracellular domain comprising a transcriptional regulator, wherein binding of the selected ligand to the extracellular ligand-binding domain induces cleavage at a ligand-inducible proteolytic cleavage site disposed between the transcriptional regulator and the linking polypeptide, and wherein the chimeric polypeptide does not comprise a Notch NRR or HD of a Notch receptor.
Thus, one difference between independent claim 1 of the examined application and the ‘685 application is that the ‘685 application does not comprise specific domains (NRR or HD) of a Notch receptor while the current application does not comprise any sequences from a Notch receptor. Hence, the ‘685 application is a species of overlapping subject matter claimed in the current application.
Claim 1 of the ‘685 application is also similar in scope to newly amended Claim 1 and new claims 82-83 of the instant application in that both sets of claims include a stop-transfer sequence. Regarding claims 1 and 82-83 of the instant application, drawn to a heterologous STS- heterologous to the TMD and comprises a sequence having at least 90% sequence identity to a STS sequence from CSF1R, CXCL16, DAG1, GHR, PTPRF, AGER, KL, NRG1, LRP1B, Jag2, EPCAM, KCNE3, CDH2, NRG2, PTPRK, BTC, EPHA3, IL1R2, or PTPRM; claim 1 of the ‘685 application requires any stop-transfer sequence. But, the specification of the ‘685 application teaches [0077] that in some embodiments, the STS includes a sequence having at least 70% sequence identity, such as, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or 99% sequence identity to a STS sequence from Notch1, Notch2, Notch3, Notch4, CSF1R, CXCL16, DAG1, GHR, PTPRF, AGER, KL, NRG1, LRP1B, Jag2, EPCAM, KCNE3, CDH2, NRG2, PTPRK, BTC, EPHA3, IL1R2, or PTPRM. The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim.
Further, the ‘685 application teaches [0072] that transmembrane domains from Type 1 transmembrane receptors IL1R1, IL1R2, IL6R, INSR, ERN1, ERN2, JAG2, KCNE1, KCNE2, KCNE3, KCNE4, KL, CHL1, PTPRF, SCN1B, SCN3B, NPR3, NGFR, PLXDC2, PAM, AGER, ROBO1, SORCS3, SORCS1, SORL1, SDC1, SDC2, SPN, TYR, TYRP1, DCT, VASN, FLT1, CDH5, PKHD1, NECTIN1, PCDHGC3, NRG1, LRP1B, CDH2, NRG2, PTPRK, SCN2B, Nradd, and PTPRM. These domains would naturally include an amino acid sequence having at least 80% sequence identity to any one of SEQ ID NOS: 1-84, 178, 182-185, and 190-192 as set forth in claim 32 of the instant application.
Further, Claim 32 of the ‘685 application defines the stop-transfer sequence as having 80% identity to SEQ ID NO:11. SEQ ID NO:11 is “RKRRR”. This matches to SEQ ID NO:90 of the instant application which is “KRRR”.
Claims 3-4, 8, 10, and 12 of the ‘685 application are all similar in scope to the claims in the examined application.
Recombinant nucleic acids, cells, cell cultures, and methods of use are overlapping between the two applications.
Applicants argue (Remarks, page 12) that as neither the claims in the present application nor the claims in the '931, '687, and '685 applications have been indicated as being otherwise in condition for allowance, Applicant respectfully submits that consideration of whether or not there are any concerns regarding obviousness-type double patenting is premature. Accordingly, Applicant requests that any rejection on the grounds of nonstatutory obviousness-type double patenting be held in abeyance. This argument has been considered but is not found persuasive as the reply by the applicant or patent owner must be reduced to a writing which distinctly and specifically points out the supposed errors in the examiner’s action and must reply to every ground of objection and rejection in the prior Office action. See 37 CFR 1.111.
Conclusion
No claim is allowed.
Applicant's amendments 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 GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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