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 .
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 09/15/2025, in which claims 1, 6, 8, 14, 16, 20, 32, and 71 are amended and 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, is acknowledged. 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 06/27/2025 has been considered by the examiner.
Withdrawn Objections and Rejections
In the office action dated 05/14/2025,
The drawings (FIG. 5 and FIG. 8A-8B) were objected to for inconsistent naming conventions. Applicant’s submission of amended replacement drawings have overcome the objections and the objections are withdrawn.
The specification was objected to for informalities in the text and using trade names or marks used in commerce without appropriate symbols indicating use in commerce. Applicant’s submission of an amended specification with appropriate corrections has overcome the objections and the objections are withdrawn.
Claims 1, 6, 14, 16, 20, and 71 were objected to for typographical errors. Applicant’s amendment to the claims have overcome the objections and the objections are withdrawn.
Claim 8 was rejected under 112(b) for insufficient antecedent basis on recited term “the cell.” Applicant’s amendment to the claim to shift claim dependency to claim 7 which recites “a cell” has overcome the rejection and the rejection is withdrawn.
Claims 1-3, 6-11, 13-14, 16, 19-21, 23, 28, 33, 37, 47, 51, and 70-71 were rejected under 102(a)(1). Applicant’s cancellation of claims 2 and 23 have rendered this rejection moot and the rejections for these are withdrawn. Applicant’s amendment to the claim to incorporate an stop transfer sequence (STS) having at least 90% sequence identity to recited STS sequences has overcome the rejections and the rejections (as previously stated) are withdrawn.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.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The instant claim is drawn to STS sequences that have various lengths less than 10 amino acids long (SEQ ID NOs: 96, 136, and 137). It is unclear how to achieve “at least 90% identity” in sequences that would only result in non-integers between 90-99% identity. Thus the claim is indefinite. See MPEP § 2173.05(c)(II).
Claim Rejections - 35 USC § 112(d)
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claim 32 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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. The instant claims at least 80% sequence identity to recited STS sequences which broadens the scope of the base claim 1, which recites 90% identity to the recited STS sequences. For examination purposes, examiner has interpreted the claim based on the limitation as presented in the base claim “at least 90% sequence identity.” Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
The factual inquiries 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.
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. 103 as being unpatentable over Emtage (WO 2019/164979 A1) and Yang (Nature. 2019;565(7738):192-197).
Through broadest reasonable interpretation of base claim 1, the TMD is only heterologous when the linking sequence is a Notch JMD and, for all other linking sequences claimed, that the TMD is not derived from Notch1. Emtage teaches a chimeric transmembrane receptor (synPTPR) with scFv extracellular binding domain targeting CD19 (defined as a pathogen ligand in the instant disclosure; ¶ [0068]; recited in claim 10) and an intracellular transcription factor (activator gal4-vp64) fused to a various types of receptor-like protein tyrosine phosphatase (PTPR) cores (TMD and first two most membrane proximal fibronectin domains - e.g. PTPRK, PTPRF, and PTPRM; Table 1) via GS-linkers (i.e. polypeptides between 2-40 amino acids), where ligand binding initiates proteolytic cleavage dependent on gamma-secretase (page 13-14, page spanning ¶; FIG1(shown below) and FIG4). Nucleic acids encoding these receptors were generated and cells (Jurkat (page 92, ¶ 3) or primary T-cells (page 148, ¶ 1)) were transduced with the constructs and rested at least 24h in culture (i.e. cell culture comprising recombinant cells and media) before various functional assays. Functional assays were performed by co-culturing with CD19 expressing cells (low expressing K562 cells or high expressing Raji cells) (page 97, ¶ 3). Positive contact with ligand (CD19) and downstream receptor cleavage of the intracellular transcriptional regulatory domain was measured by the expression of GFP encoded by reporter nucleic acid (i.e. modulating activity of the cell through expression of GFP; page 149, ¶ 1).
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424
648
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Emtage teaches the synPTPR constructs are to be functionally expressed at the cell membrane (Figure 8 and 10), and the PTPR core sequences contain stop transfer sequences (STS) as part of the TMD as evidenced by the core sequences, however the STS shares less than 90% identity (~83% identity).
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199
1062
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While Emtage also teaches the chimeric transmembrane receptors in some embodiments can include at least on intracellular regulatory domain that is present in a Notch protein (page 33, lines 13-14), Emtage does not specify this to include the intracellular JMD (containing the STS sequences as instantly claimed).
Yang teaches Notch1 residues 1755-1761 (i.e. residues in instant SEQ ID NO: 96) forms a β-strand that creates hydrogen bonds with the β2 strand and the loop connecting TM8 and TM9 of presenilin 1 (PS1) subunit of gamma-secretase (PAL motif), interactions of which were observed to be important for stabilizing substrate binding and orientation for cleavage through formation of a hybrid β-sheet (page 195, left column, ¶ 2). Similar to Notch1, another gamma secretase substrate, amyloid precursor protein (APP), has a cleavage site three residues upstream of hydrophilic sequences, and deleting the PAL motif in gamma secretase abrogated proteolytic activity towards APP (page 195, right column, ¶ 4-5).
One of ordinary skill in the art would recognize the modular nature of a synthetic receptor as taught by Emtage. Also, one of ordinary skill would recognize that a naturally derived intracellular JMD sequences from gamma secretase substrate receptors (i.e. Notch1, CLSTN1, CLSTN2, and Notch2 as recited in instant SEQ ID NOs: 96, 135, 136, and 137) comprising characteristic adjacent hydrophilic residues would predictably retain stabilizing interactions with the catalytic PS1 subunit of gamma secretase as taught by Yang. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention that known intracellular JMDs sequence for gamma secretase substates (i.e. SEQ ID NOs: 96 and 135-137) can be substituted for the intracellular JMD residues in the synPTPR receptor as taught by Emtage with a reasonable expectation of success of maintaining receptor cleavability.
Claims 24 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Emtage and Yang as applied to claims 1 and 28 above, and further in view of Guedan (Mol Ther Methods Clin Dev. 2018;12:145-156).
The combined teachings of Emtage and Yang teach claim 1 and 28 as discussed above.
However, neither reference discloses a linker at least 80% identical to instant SEQ ID NO:97-99 or 138-148.
Guedan teaches that CARs are “designed in a modular fashion” typically consisting of ECD, a hinge region, TMD, and one or more ICDs to transmit activation signals (page 145-146, page spanning ¶). Guedan teaches that incorporating Ig-like domain hinges increases CAR stability for efficient expression and activity (page 146, column 2, ¶ 3); specifically, hinge domains that lack Fc gamma receptor binding activity (e.g. CD8α and CD28; instant SEQ ID NOs: 138 and 139, respectively) preventing immunogenicity (page 147, column 1, ¶ 1).
One of ordinary skill in the art would recognize that a naturally derived hinge domain as taught by Guedan is functionally equivalent to synthetic GS-linker as taught by Emtage, and may provide lower immunogenicity as a naturally occurring sequence. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention that the GS linker between ligand binding domain and transmembrane domain as taught by Emtage could be substituted for a naturally occurring hinge domain as taught by Guedan to generate a functional CAR with a reasonable expectation of success.
Claims 48, 58, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Emtage and Yang as applied to claim 1, 33, and 37 above, and further in view of Roybal (Cell. 2016;167(2):419-432.e16).
The combined teachings of Emtage and Yang teach claims 1, 33, and 37 as discussed above. Moreover, Emtage teaches the PTPR core is similar to Notch core in that it in theory first requires S2 cleavage by an ADAM protease before gamma secretase cleavage (page 7-8, page spanning ¶). However the synPTPR construct is advantageous over existing synNotch technology by virtue of its smaller construct size and stable sensitivity to low and high concentration of antigen (page 10, ¶ 2; figure 3).
While Emtage discloses pharmaceutical compositions comprising either nucleic acid encoding synPTPR or recombinant cells expressing synPTPR (claims 17-19) and discloses these can be used as a method of treating disease (claim 20) (e.g. cell recognizes a target cell expressing the target antigen and effectively acts on the target cell by mediating an increased immune response against the cell through secretion of cytokines (page 76, ¶ 3), Emtage does not explicitly teach these in practice.
Roybal teaches a engineered T cell transfected with synNotch receptor containing a customizable ligand binding domain that detects a cell-surface antigen of interest (scFv targeted to CD19 or Her2 or nanobodies to GFP), the core regulatory region of Notch (Notch juxtamembrane domain (JMD) and transmembrane domain (TMD)) that controls proteolysis (gamma secretase dependent; page 420, column 2, ¶ 1), and a cytoplasmic orthogonal transcription factor (e.g. Gal4 VP64) (Figure 1 and Figure 1 legend). Roybal teaches that CAR activation through proteolytic cleavage of an intracellular domain can drive-antigen induced custom cytokine programs, expression of therapeutics, bias T cell differentiation to anti-tumor Th1 fate, and stimulate endogenous immunity in mouse tumor models (Figures 2-6).
One of ordinary skill in the art would recognize that the synthetic CARs as taught by Emtage and Roybal are modular and that domains can be interchanged. Emtage confirms the signaling potential of synPTPR core receptors and an artisan would be motivated to use a synPTPR core over first generation synNotch core as Emtage teaches the smaller overall construct size would facilitate better transduction efficiency. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to generate a pharmaceutical composition utilizing synPTPR as taught by Emtage and that this product would predictably generate similar activity of inhibiting target tumor cell growth (i.e. treating a health condition) similar to analogous synNotch constructs with a reasonable expectation of success.
Response to Arguments - 35 USC § 103
Applicant's arguments filed 09/15/2025 have been fully considered but they are not persuasive.
Applicant states:
“Emtage fails to teach or suggest a chimeric polypeptide " ... wherein the transmembrane domain further comprises a stop-transfer sequence (STS) comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 96, 135, 136, or 137" as recited in amended claim 1.” (Remarks, page 13, ¶ 3)
“Guedan fails to overcome this deficiency of Emtage.” (Remarks, page 13, ¶ 3)
“Roybal fails to overcome this deficiency of Emtage.” (Remarks, page 14, ¶ 3)
In response to applicant’s argument regarding the amended claim 1, the current rejection has been modified to address the amended claim limitations as discussed above. Briefly, Yang teaches hydrophilic residues directly following the TMD in known gamma secretase substrates, Notch 1 and APP, act to stabilize interactions with PS1, the catalytic subunit of gamma secretase. Therefore, a skilled artisan would have a reasonable expectation of success in simple substitution of known STS sequence that flank the TMD from naturally occurring gamma secretase transmembrane substrate (e.g. Notch1, CLSTN1, CLSTN2, or Notch2) within the synPTPR receptor as taught by Emtage with a reasonable expectation of maintaining receptor cleavability. Subsequent arguments regarding additional references not curing this deficiency, as discussed above, are therefore also deemed unpersuasive.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
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 (previously US 17/217,635)
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 allowed.
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. 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