ETAILED 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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/05/2026 has been entered.
Priority
This application is a U.S. national phase of International Application No. PCT/US2020/052320, filed on 09/23/2020, which claims domestic benefit to US provision application 62/905,258, filed 09/24/2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
The Amendment, filed on 06/05/2026, is acknowledged in which:
Claims 2, 4-5, 12, 15, 17-18, 22-23, 25-27, 29-31, 34-36, 38-46, 49-50, 52-57, 59-60, and 62-69 are canceled.
Claims 1, 32, and 71 are currently amended.
Claims 3, 6-11, 13-14, 16, 19-21, 24, 28, 33, 37, 47-48, 51, 58, 61, and 70 were previously presented.
Claims 1, 3, 6-11, 13-14, 16, 19-21, 24, 28, 32-33, 37, 47-48, 51, 58, 61, and 70-71 are pending in the instant application and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/17/2026 has been considered by the examiner.
Withdrawn Objections and Rejections
In the office action dated 01/05/2026,
Claim 1 was rejected under 112(b) for ambiguity regarding 90% sequence identity to sequences that would result in non-integer values. Applicant’s amendment to the claim to recite 100% identity to recited sequences has overcome the rejection and the rejection is withdrawn.
Claim 32 was rejected under 112(d) for failing to further limit dependent base claim 1. Applicant’s amendment to the claim to remove sequence variability in recited STS sequences has overcome the rejection and the rejection is withdrawn.
1, 3, 6-11, 13-14, 16, 19-21, 28, 33, 37, 47, 51, and 70-71 were rejected under 35 U.S.C. 103 as being unpatentable over Emtage and Yang. Applicant’s amendment to the base claim to remove limitation (v) and to recite specific STS sequences has overcome the rejections, as previously stated, and the rejections are withdrawn. However, upon further consideration, new grounds of rejection are made in view of newly found prior art, necessitated by applicant’s amendment.
The following grounds of objections and/or rejections are either maintained or necessitated by applicant’s amendment to the claims. Please note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
New - Drawings
Color photographs and color drawings (FIG. 9, which makes reference to blue and red panels; ¶ [0032]) are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
New - Claim Rejections - 35 USC § 112(a)
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, 3, 6-11, 13-14, 16, 19-21, 28, 33, 37, 47, 51, and 70-71 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for heterologous SynNotch and MiniNotch receptors comprising 100% identity to Notch1 juxtamembrane domains (JMDs) with or without NRR, respectively, with swapped transmembrane domains (TMDs) and Notch 1 stop transfer sequence (STS) (SEQ ID NO: 96) (i.e. constructs with evidence of successful surface expression and cleavage as disclosed in FIGs 3-6), truncated CD8 hinge-CLSTN1 TMD-Notch1 STS (pTMD201), and truncated CD8 hinge-CLSTN2 TMD-Notch1 STS (pTMD202), 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 (i.e. functional requirement), does not reasonably provide enablement for any other chimeric polypeptides as claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc. 8 USPQD2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is a conclusion reached by weighing several factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQQ2d 1400 (Fed. Cir. 1988) and include the following:
State of the prior art and unpredictability: At the time of filing, it was known that classical synNotch receptors are prone to ligand-independent activation. Yang (Commun Biol. 2020;3(1):116) teaches that, in conventional synNotch receptors, scFv recognition induces conformational change of the NRR and TMD exposing S2 and S3 cleavage sites for sequential cleavage by ADAM and γ-secretase to release the intracellular domain of the receptor for subsequent downstream signaling (pg 2, left column, ¶ 2). However, Yang references several studies (prior art) that show synNotch cells are prone to ligand-independent activation (LIA), especially in instances with high receptor expression (i.e. synNotch cells require a labor-intensive clonal selection against sender cells that do not express the antigen) (pg 2, left column, ¶ 3).
Moreover, regarding sequentially cleaved substrates, prior art teaches ectodomain structure dictates interactions. Bolduc (PNAS USA. 2016;113(5):E509-E518) teaches the nicastrin subunit of γ-secretase acts to sterically block substrates with large ectodomains from interacting with γ-secretase reinforcing a mechanism by which γ-secretase recognition and cleavage is generally limited to ectodomain-shed substrates (abstract), suggesting additional enzyme interactions dictate the success of intracellular domain release by γ-secretase.
Zhang (J Biol Chem. 2002;277(17):15069-15075) teaches that swapping the ectodomain of similar γ-secretase substrate APP TMD can have unpredictable effects to cleavage. While Zhang teaches a Notch-TMD substitution (SW-m-Notch) can maintain substrate cleavage in a chimeric-APP, the same was not the case in pre-TMD substitutions (Figure 1B, Figure 2B, Figure 5A). Zhang teaches α-regions from Notch1 (aa 1716-1734), APLP-2, and HER-3 fused to APP TMD (SW-α-Notch), levels of Aβ-like peptides released (i.e. cleaved product) were substantially decreased (pg 15071, left column, “Chimeric DNA Construction”; pg 15072, right column, ¶ 2), suggesting the pre-TMD plays an role in the ability of γ-secretase to recognize and properly cleave its substrate though the mechanism, such as whether this domain comprises a binding site for the protease or whether it alters the conformation of the intramembranous portion of the TMD, remains unclear (pg 15075, left column, ¶ 1-2). Therefore, it is unpredictable whether the Notch JMD, let alone those with up to 20% variability, would be compatible with TMDs from other γ-secretase substrates to generate chimeras capable of ligand-induced cleavage without extensive testing.
Hayward (Elife. 2019;8:e46983) teaches a Synthetic Notch Assay for Proteolytic Switches (SNAPS) to screen protease site-containing juxtamembrane domains for their ability to functionally substitute for Notch’s proteolytic switch and induce transcription in response to cell-cell contact (i.e. shedding in chimeric Notch receptors). Hayward observed some Notch JMD structural homologous could functionally substitute for the Notch NRR for ligand-induced signaling (Dag, PCDH15, and CDHR2), though other homologues exhibited lack of response from absence of proteolysis (MUC13) or high levels of proteolysis even in the absence of ligand (MUC1 and IA-2) (i.e. constitutively proteolyzed) (Figure 1). Hayward predicts that lack of structured neighboring domains within the JMD would likely lead to more dynamic domains where protease site exposure occurs more frequently therefore increasing propensity of conformational changes independent of ligand binding (pg 10, ¶ 2). Additional chimeric receptors with diverse JMD types also yielded varying effects on ligand dependent signaling. Notably, despite similar fibronectin type III domains (i.e. like those in ROBO1 JMD as instantly claimed) in JMDs derived from AXL, TYRO3, and MERTK, chimeric receptors using MERTK had no detectable cleavage despite positive cell surface expression, lending to the unpredictability of swapping similar JMD domains (Figure supplement 5).
Thus, the evidence of record indicates that the mixing and matching of any given domain that might be considered within scope of any given “linking sequence” (i)-(iv) with any given type 1 receptor with a ligand-dependent cleavable transmembrane domain as currently claimed, would require significant empirical experimentation to establish operative embodiments other than those explicitly disclosed.
Direction provided by the inventor: The guidance and working examples in the specification is not commensurate with the scope of the claimed invention. Examples and description are limited to heterologous transmembrane domains corresponding to transmembrane domains from known γ-secretase targets (¶ [0172]) in three different chimeric receptors types – (1) “SynNotch” using Notch1-JMD, (2) “MiniNotch” using NRR deleted Notch1-JMD, and (3) “HingeNotch” which uses CD8 hinge sequence with a Notch1 STS, though the HingeNotch receptor only ever uses CLSTN1/2 TMDs (Example 11). Moreover, based on the disclosure, despite purported shared function of the tested TMDs as γ-secretase substrates, it is clear from the examples provided that this alone is insufficient to predict the functionality of generated chimeric receptors as trial-and-error testing shows many do not produce functional receptors based on reporter assays (FIGs 3-6).
Nature of the invention and Breadth of claims: The claims are directed to chimeric polypeptides comprising: (a) an extracellular binding domain (ECD) with affinity for a selected ligand; (b) a linking sequence having at least 80% identity to (i) a Notch JMD, (ii) a LNR and/or HD deleted Notch JMD, (iii) a polypeptide hinge domain, or (iv) a ROBO1 JMD; (c) a type 1 receptor transmembrane domain comprising ligand-inducible proteolytic cleavage sites; and (d) and an intracellular domain comprising a transcriptional regulator, wherein binding of the selected ligand to the ECD induces cleavage at the ligand-inducible cleavage site, and wherein: (1) when the linking sequence is Notch derived the TMD is heterologous; and (2) when the linking sequence is not Notch derived the TMD is not Notch1; and wherein the TMD comprises an STS comprising an amino acid sequence of SEQ ID NO: 96, 135, 136, or 137 (derived from Notch1, CLSTN1, CLSTN2, or Notch 2, respectively). This breadth is not supported in the specification because while the disclosure teaches general methods of making and testing said chimeric receptors, it does not set forth the manner and process of making commensurate with the scope of protection sought (e.g. disclose a common structure for the genus claimed that would predictably perform the claimed ligand-induced cleavage based signaling).
Quantity of experimentation needed: Given the above information, it is clear that one of skill in the art would not be enabled to make or use the full scope of the invention - any JMD+TMD with functional ligand-induced cleavage as claimed - without undue experimentation. The unpredictability of the art at the time of filing and lack of adequate description of structure/function information within the instant disclosure does not allow one of ordinary skill to reliably predict functional embodiments without rigorous testing. As undue experimentation is required, claims 1, 3, 6-11, 13-14, 16, 19-21, 28, 33, 37, 47, 51, and 70-71 are not fully enabled by the disclosure.
Maintained - Double Patenting
US 11,202,801 B2
Claims 1, 3, 7-11, 14, 16, 19-21, 24, 33, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-12, 14-15, 21-25, and 27-30 of U.S. Patent No. US 11,202,801 B2 (herein US801). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 US801 claims a chimeric polypeptide comprising from N- to C-terminus: a ligand binding ECD, hinge domain from CD8α linker, a Notch (Type 1 receptor as acknowledged in the instant disclosure; ¶ [0006]) TMD without NRR components (LNR and HD) comprising a proteolytic cleavage site, and an ICD comprising a transcriptional regulator that is cleaved upon ligand binding. Broadest reasonable interpretation of the reference claim indicates that the TMD can be derived from any Notch receptor as evidenced by subsequent US801 claims 28-30 claiming the Notch TMD is Notch 2, 3, or 4 derived (i.e. heterologous Notch JMD and TMD pairings as specified by the limitations from instant claim 1(d)(i-ii) and SEQ ID NO:137 (STS of Notch2)). Therefore, US801 claim 1 is patentably indistinct from instant claim 1.
Subsequent dependent claims recite elements identical or within scope to the instant claims and are therefore also patentably indistinct as follows:
Claim #
Instant
US801
General claim description
3 & 19
11
γ-secretase cleavage site
7
3
Binding cell surface ligand
8
5
Cell is a tumor cell (i.e. pathogen as defined by instant spec ¶ [0068])
9
6
Ligand comprises a protein or carbohydrate
10
7
Ligand selected from… (identical group list)
11
8
Ligand selected from… (identical group list)
14
9
Antigen binding moiety selected from… (identical group list)
16
10
TAA selected from… (identical group list)
20 & 21
12
ICD comprises identical group of transcriptional regulators/activators
24
22-26
Identical CD8α hinge domains:
---
33
14
Nucleic acid encoding chimeric receptor
37
15
Recombinant cell comprising chimeric receptor
US 11,617,766 B2
Claims 1, 3, 7-11, 14, 16, 19-21, 24, 33, 37 and 61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-12, 14-15, 21-25, and 27-29 of U.S. Patent No. US 11,617,766 B2 (herein US766). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 US766 claims a chimeric polypeptide comprising from N- to C-terminus: a ligand binding ECD, hinge domain from CD8α, CD28, OX40 or IgG4, a Notch TMD (Type 1 receptor as acknowledged in the instant disclosure; ¶ [0006]) without NRR components (LNR and HD) comprising a proteolytic cleavage site, an ICD comprising a transcriptional regulator that is cleaved upon ligand binding. Broadest reasonable interpretation of the reference claim indicates that the TMD can be derived from any Notch receptor and not necessarily from Notch 1 as evidenced by subsequent US766 claims 27-29 claiming the Notch TMD is Notch 2, 3, or 4 derived (i.e. heterologous Notch JMD and TMD pairings as specified by the limitations from instant claim 1(d)(i-ii); and SEQ ID NO:137 (STS of Notch2)). Therefore, US766 claim 1 is patentably indistinct from instant claim 1.
Subsequent dependent claims recite elements identical or within scope to the instant claims and are therefore also patentably indistinct as follows:
Claim #
Instant
US766
General claim description
3 & 19
11
γ-secretase cleavage site
7
3
Binding cell surface ligand
8
5
Cell is a tumor cell (i.e. pathogen as defined by instant spec ¶ [0068])
9
6
Ligand comprises a protein or carbohydrate
10
7
Ligand selected from… (identical group list)
11
8
Ligand selected from… (identical group list)
14
9
Antigen binding moiety selected from… (identical group list)
16
10
TAA selected from… (identical group list)
20 & 21
12
ICD comprises identical group of transcriptional regulators/activators
24
22-25
Identical hinge domains:
--
33
14
Nucleic acid encoding chimeric receptor
37
15
Recombinant cell comprising chimeric receptor
61
21
Method for treating of health condition comprising administering recombinant cells
US 11,897,932 B2
Claims 1, 3, 7-11, 14, 16, 21, 24, and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-33, 35-41, 43-47, and 49-50 of U.S. Patent No. 11,897,932 B2 (herein US932). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 US932 claims a chimeric polypeptide comprising from N- to C-terminus: a ligand binding scFv ECD, a linking polypeptide comprising SEQ ID NO:19 (identical to instant SEQ ID NO:98 – “MiniNotch” JMD), a Notch (Type 1 receptor as acknowledged in the instant disclosure; ¶ [0006]) TMD comprising a proteolytic cleavage site, an ICD comprising a transcriptional regulator that is cleaved upon ligand binding, a means for linking the ECD to and the TMD, and wherein the chimeric protein does not have Notch NRR components (LNR and HD). Broadest reasonable interpretation indicates that the TMD can be derived from any Notch receptor so long as the sequence is heterologous to the linker as further evidenced by subsequent US932 claims 32-34 claiming the Notch TMD is human Notch 2, 3, or 4 derived (i.e. heterologous Notch JMD and TMD pairings as specified by the limitations from instant claim 1(d)(i-ii)). Claim 2 of US932 further claims the TMD comprises and STS, which if derived from Notch 2 as stated above would comprise a sequence within scope of the instant claim (instant SEQ ID NO:137 derived from Notch 2).
Subsequent dependent claims recite elements identical or within scope to the instant claims and are therefore also patentably indistinct as follows:
Claim #
Instant
US932
General claim description
3 & 19
11
γ-secretase cleavage site
7
3
Binding cell surface ligand
8
5
Cell is a tumor cell (i.e. pathogen as defined by instant spec ¶ [0068])
9
6
Ligand comprises a protein or carbohydrate
10
7
Ligand selected from… (overlapping group list)
11
8
Ligand selected from… (identical group list)
16
10
TAA selected from… (overlapping group list)
21
12
ICD comprises identical group of transcriptional regulators
37
15
Recombinant cell comprising chimeric receptor
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
US 17/762,685
Claims 1, 3, 7-11, 13-14, 16, 20-21, 33, 37, 47-48, 51, 58, 61, and 70-71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 8-10, 12-13, 15, 19-20, 32, 36, 40, 51, 52, 55, 62, 66, and 75-76 of copending Application No. 17/762,685 (herein US685). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 US685 claims a chimeric polypeptide comprising from N- to C-terminus: a ligand binding ECD, a linking polypeptide, a TMD comprising a proteolytic cleavage site (i.e. dispose between linking polypeptide and ICD), and ICD comprising a transcriptional regulator that is cleaved upon ligand binding, wherein the chimeric receptor does not comprise Notch NRR components (LNR and HD). Broadest reasonable interpretation of the reference claim does not limit the TMD, which could therefore include type 1 receptor TMDs as claimed. Claim 33 further claims an identical STS (SEQ ID NO:11 identical to instant SEQ ID NO:96)
Subsequent dependent claims recite elements identical or within scope to the instant claims and are therefore also patentably indistinct as follows:
Claim #
Instant
US685
General claim description
3 & 19
18
γ-secretase cleavage site
7
3
Binding cell surface ligand
8
4 & 6
Cell is a pathogen or tumor cell (i.e. pathogen as defined by instant spec ¶ [0068])
9
8
Ligand comprises a protein or carbohydrate
10
9
Ligand selected from… (overlapping group list)
11
10
Ligand selected from… (identical group list)
13
12
ECD comprises ligand binding portion of receptor
14
13
Antigen binding moiety selected from… (identical group list)
16
15
TAA selected from… (identical group list)
20
19
ICD transcriptional regulators comprises transcriptional activator or repressor
21
20
ICD comprises identical group of transcriptional regulators
28
33
TMD with sequence identity to SEQ ID NO:27 (identical to instant SEQ ID NO:57)
33
36
Nucleic acid encoding chimeric receptor
37
40
Recombinant cell comprising chimeric receptor
47
51
Cell culture of aforementioned recombinant cell, and culture media
48
52
Pharmaceutical composition of recombinant nucleic acid
51
55
Method for modulating cell activity
58
62
Method for inhibiting cell activity of target cell
61
66
Method for treating of health condition comprising administering recombinant cells
70
75
System for modulating activity of a cell
71
76
Method for making recombinant cell
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
US 17/995,751
Claims 1-3, 7-11, 13-14, 16, 23, 24, 28, 33, 37, 48, 51, 58, 61, and 70-71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6, 8, 12-13, 15, 18, 34, 40, 41, 49, 54, 68, 92, 95, 100, and 102 of copending Application No. 17/995,751 (herein US751). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 US751 claims a chimeric polypeptide comprising from N- to C-terminus: a ligand binding ECD, hinge domain capable of promoting oligomer formation of the chimeric polypeptide via intermolecular disulfide bonding (e.g. naturally occurring immunoglobin-like domains; ¶ [0096]), a TMD comprising a proteolytic cleavage site (i.e. between the transcriptional effector and hinge domain), an ICD comprising a transcriptional regulator that is cleaved upon ligand binding, and wherein the chimeric protein does not have Notch NRR components (LNR and HD). Broadest reasonable interpretation of the reference claim does not limit the TMD, which could therefore include type 1 receptor TMDs as claimed. Furthermore, the recitation of specific species of transcriptional effector as recited in US751 claim 1(d) anticipates the instantly claimed broad genus of a “transcriptional regulator.” Claims 2 and 40 of US751 further claims the TMD comprises an STS with sequences identical to those recited in the instant claim (SEQ ID NO: 37 and 31 identical to instant SEQ ID NO:96 and 137, respectively).
Subsequent dependent claims recite elements identical or within scope to the instant claims and are therefore also patentably indistinct as follows:
Claim #
Instant
US751
General claim description
3,19
18
γ-secretase cleavage site
7,8
3
Binding cell surface ligand, wherein the cell is a pathogen
9,11
8
Ligand comprises a protein, carbohydrate; is selected from cell surface receptors, etc. and/or is a TAA or tumor specific antigen
13
12
ECD comprises ligand binding portion of receptor
14,16
13
Antigen binding moiety selected from… (identical group list) and/or specifically binds to (overlapping list of TAAs)
24
34,100
Hinge derived from CD8α (i.e. instant SEQ ID NOs: 138, and 142-148) or 80% sequence identity to SEQ ID NO:15 (identical to instant SEQ ID NOs:99)
28
41,102
TMD domain with identical sequences:
---
33
49
Nucleic acid encoding chimeric receptor
37
54
Recombinant cell comprising chimeric receptor
48
68
Pharmaceutical composition of recombinant nucleic acid
51,58,61, 70
95
Method for modulating cell activity, inhibiting target cell activity, or treating a health condition, comprising administering chimeric polypeptide, recombinant nucleic acid, recombinant cell, or a pharmaceutical composition containing any of the aforementioned elements
71
92
Method for making recombinant cell
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
US 18/178,440
Claims 1-3, 7-11, 14, 16, 21, 28, 33, and 37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-33, 35-41, 43-47, and 49-50 of copending Application No. 18/178,440 (herein US440). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 31 US440 claims a chimeric polypeptide comprising from N- to C-terminus: a ligand binding ECD, a Notch (Type 1 receptor as acknowledged in the instant disclosure; ¶ [0006]) TMD comprising a proteolytic cleavage site, an ICD comprising a transcriptional regulator that is cleaved upon ligand binding, a means for linking the ECD to and the TMD, and wherein the chimeric protein does not have Notch NRR components (LNR and HD). Broadest reasonable interpretation indicates that the TMD can be derived from any Notch receptor so long as the sequence is heterologous to the linker as further evidenced by subsequent US440 claims 44-46 claiming the Notch TMD is human Notch 2, 3, or 4 derived (i.e. heterologous Notch JMD and TMD pairings as specified by the limitations from instant claim 1(d)(i-ii)). Claim 32 further claims the TMD comprises an STS, which if derived from Notch 2 as stated above would comprise a sequence within scope of the instant claim (instant SEQ ID NO:137 derived from Notch 2).
Subsequent dependent claims recite elements identical or within scope to the instant claims and are therefore also patentably indistinct as follows:
Claim #
Instant
US440
General claim description
3 & 19
41
γ-secretase cleavage site
7
33
Binding cell surface ligand
8
35
Cell is a tumor cell (i.e. pathogen as defined by instant spec ¶ [0068])
9
37
Ligand comprises a protein or carbohydrate
10
38
Ligand selected from… (overlapping group list)
11
39
Ligand selected from… (identical group list)
14
36
Antigen binding moiety selected from… (identical group list)
16
40
TAA selected from… (identical group list)
21
47
ICD comprises identical group of transcriptional regulators
28
43
TMD with sequence identity to SEQ ID NO:17 (identical to instant SEQ ID NO:57)
33
49
Nucleic acid encoding chimeric receptor
37
50
Recombinant cell comprising chimeric receptor
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments - Double Patenting
Applicants are reminded 37 CFR 1.111 requires that replies by applicant or patent owner must reply to every ground of objection and rejection in the prior Office action. Only objections or requirements as to form not necessary to further consideration of the claims may be requested to be held in abeyance until allowable subject matter is indicated. Non-statutory double patenting rejections may not be held in abeyance. See MPEP 714.02. Applicants did not traverse the NSDP rejection. The rejection is maintained (or modified).
Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNAH SUNSHINE whose telephone number is (571)270-7417. The examiner can normally be reached M-Th & Second Friday 8:30am-5pm EST.
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/HANNAH SUNSHINE/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
