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
This action is in response to the papers filed June 22, 2026.
Claim Amendments
Applicant’s amendment to the claims filed on 06/22/2026 is acknowledged.
Claims 1-56, 59, 65-68, 73-75 have been cancelled.
Claims 57 and 64 are amended.
Claims 57-58, 60-64, 69-72 and 76 are pending and under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements in the application. See the Requirement for Restriction/Election mailed 01/02/2025.
Applicant elected without traverse Group 1, drawn to a chimeric receptor comprising an extracellular domain of G-CSFR, and a nucleic acid encoding thereof, an expression vector comprising thereof, a cell comprising thereof, and a kit comprising thereof, in the reply filed 04/01/2025.
Applicant further elected without traverse a chimeric receptor comprising a G-CSFR extracellular domain according to SEQ ID NO: 5 (amino acid sequence) and SEQ ID NO: 6 (nucleic acid sequence), a G-CSFR transmembrane domain according to SEQ ID NO: 8 (amino acid sequence) and SEQ ID NO: 12 (nucleic acid sequence), a G-CSFR intracellular domain according to SEQ ID NO: 20 (amino acid sequence), and an IL-2Rβ intracellular domain according to SEQ ID NO: 21 (amino acid sequence). The elected construct corresponds to the “G2R-3” construct as described in the specification and depicted in Figure 4:
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Priority
The instant application 17/767,687 was filed on 04/08/2022. This application is a national stage of international application PCT/CA2020/051346 filed 10/08/2020, claiming priority based on U.S. Provisional Application 62/912,223 filed 10/08/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/22/2026 has been considered.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 03/23/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
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.
Claims 57-58, 60-63, 69-72, and 76 are rejected under 35 U.S.C. 103 as being unpatentable WO 94/22914 to Greenberg et al., in view of US 2019/0292533 A1 to Nager et al.; and US 2018/0044399 A1 to Rajpal et al.
This rejection is newly applied, necessitated by amendment.
As discussed above in this action, applicant’s elected chimeric receptor corresponds to the “G2R-3” construct as described in the specification and depicted in Figure 4:
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Prior to the effective filing date of the instantly claimed invention, Greenberg describes chimeric cytokine receptors which enable lymphocytes to proliferate in response to an alternative cytokine, preferably a cytokine that is expressed in the lymphocyte at elevated levels in response to cognate antigen stimulation, or a cytokine that could be administered with reduced toxicity relative to, e.g., IL-2. The chimeric cytokine receptor comprises an extracellular domain of one receptor A-R fused, via a transmembrane domain, to an intracellular (cytoplasmic) domain of a second receptor B-R, thereby lessening the growth dependency of the lymphocyte on cytokine B in the presence of cytokine A. See, e.g., Abstract; pg. 5, ll. 11-18; pg. 6, ll. 20-28; and Figure 1:
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In particular, Greenberg teaches the extracellular domain is derived from G-CSFR, and the intracellular (cytoplasmic) domain is derived from IL-2Rβ. See, e.g., pg. 12, ll. 2-15. Furthermore, Greenberg discloses that suitable transmembrane domains exhibit characteristics such as hydrophobicity that promote their stable incorporation into the cellular membrane. Logically, a convenient source of such a transmembrane domain would be the transmembrane domains of receptors A-R or B-R. Preferably, therefore, the transmembrane domain is derived from cytokine receptor A-R or, more preferably, from receptor B-R. See, e.g., pg. 7, ll. 5-12; pg. 11, ll. 15-18. Accordingly, Greenberg fairly suggests that the transmembrane domain is derived from G-CSFR or IL-2Rβ.
Greenberg further discloses a nucleic acid encoding the chimeric receptor, and host cells comprising the nucleic acid. See, e.g., pg. 12, ll. 16-33.
For these reasons, Greenberg is found to teach or fairly suggest a chimeric receptor comprising the extracellular domain of G-CSFR, the intracellular domain of IL-2Rβ, and the transmembrane domain of G-CSFR or IL-2Rβ. Such a chimeric cytokine receptor comprising the intracellular domain of IL-2Rβ, as found in Greenberg, comprises the intracellular signaling domains of IL-2Rβ, including the Jak-binding regions (Box 1 and Box 2 motifs), adaptor protein SHC region, and STAT5 region.
The claimed invention recites that the chimeric receptor comprises a Box 1 region and a Box2 region of G-CSFR. Accordingly, the difference between the claimed invention and that of Greenburg is that the Jak-binding regions (Box 1 and Box 2 motifs) are derived from the receptor of the intracellular domain, IL-2Rβ, in Greenburg’s invention; whereas, the Jak-binding regions (Box 1 and Box 2 motifs) are derived from the receptor of the extracellular domain, G-CSFR, in the claimed invention.
However, prior to the effective filing date of the instantly claimed invention, Nager is considered relevant prior art for teaching chimeric cytokine receptors for improving the functional activities of immune cells, such as T cells. The chimeric cytokine receptor comprises a dimerization domain, a tyrosine activating domain, and a tyrosine effector domain; wherein the dimerization domain is an extracellular domain of a cytokine receptor; wherein the tyrosine activating domain is a transmembrane domain and a Jak-binding domain (Box 1 and Box 2 motifs) derived from a protein; wherein the tyrosine effector domain is a STAT-activation domain of a receptor. See, e.g., Abstract; par. 7-8, 10, 19, 220, 236.
Furthermore, Nager discloses that the dimerization domain may comprise the extracellular domain of G-CSFR (see, e.g., par. 20, 34, 223), the tyrosine activating domain may comprise a transmembrane domain and a Jak-binding domain of G-CSFR (see, e.g., par. 22, 25, 34, 238-239, 248), and the tyrosine effector domain may comprise a cytoplasmic tail (cytotail) of IL-2Rβ containing the STAT-activation domains thereof (see, e.g., par. 31, 252-255, 258).
Nager further describes the innovation as an improvement over the “traditional approach” to engineering cytokine receptors. While the traditional approach (Figure 10C) fuses only the extracellular domain (ectodomain) of receptor A to the transmembrane domain, Jak-binding domain and “cytotail” domain (i.e., the region after the JAK-binding domain) of receptor B, Nager’s improved approach (Figure 10D) fuses the extracellular domain (ectodomain), transmembrane domain and Jak-binding domain of receptor A to the cytotail domain of receptor B. In a working example, chimeric cytokine receptors based on the new approach showed a greater magnitude of downstream signaling relative to the traditional approach. See, e.g., Example 5C, par. 430-435; and Figures 10C-10F.
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Accordingly, Greenburg’s design of a G-CSFR/IL-2Rβ chimera follows the “traditional approach” (Figure 10C, above) described by Nager, and the claimed invention may therefore be viewed as applying Nager’s improved approach (Figure 10D, above) to designing a G-CSFR/IL-2Rβ chimera. Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the G-CSFR/IL-2Rβ chimera of Greenburg (a design following the “traditional approach”), by retaining the transmembrane domain and Jak-binding domains (Box 1 and Box 2 motifs) of the receptor of the extracellular domain, G-CSFR, in view of the teachings of Nager (improved approach), with a reasonable expectation of success because, Nager found that chimeric cytokine receptors based on the improved approach showed a greater magnitude of downstream signaling relative to the traditional approach (par. 435, Figure 10F). Moreover, as outlined above, Nager broadly teaches that G-CSFR provides suitable extracellular, transmembrane, and Jak-binding domains for a chimeric receptor, and IL-2Rβ provides a suitable cytotail (i.e., the region after the JAK-binding domain) for a chimeric receptor.
Claim 57 further recites “wherein the chimeric receptor homodimerizes upon contact with G-CSF.” As instructed by MPEP 2111.04, claim scope is not limited by claim language that does not limit a claim to a particular structure. In this case, the recitation is directed to a functional property of the claimed chimeric receptor but does not clearly or necessarily further limit the structure thereof. Accordingly, since the prior art structure is capable of performing the recited function, the prior art meets the claim. Moreover, Greenburg expressly recognizes that G-CSFR undergoes homodimerization (pg. 11, ll. 27-29), and Nager expressly teaches that the chimeric receptors undergo dimerization (par. 20, 220, 223, 486), as claimed. For these reasons, the limitation “wherein the chimeric receptor homodimerizes upon contact with G-CSF” is not found to necessarily result in a structural difference which patentably distinguishes the claimed chimeric receptor from that of the prior art.
Sequence identifiers (SEQ ID NOs):
Claim 57 further recites the that (a)the G-CSFR transmembrane domain comprises the amino acid sequence of SEQ ID NO: 8; (b) the G-CSFR Box 1 and Box2 region comprises the amino acid sequence of SEQ ID NO: 20; and (c) the IL-2Rβ intracellular domain comprises the amino acid sequence of SEQ ID NO: 21.
(a) Nager discloses that the “tyrosine kinase activating domain” (transmembrane and Jak-binding domains) of G-CSFR comprises the amino acid sequence according to SEQ ID NO: 95 (pg. 20, Table 1B), which comprises the amino acid sequence of instant SEQ ID NO: 8. See alignment:
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(b) Nager discloses that the “tyrosine kinase activating domain” (transmembrane and Jak-binding domains) of G-CSFR comprises the amino acid sequence according to SEQ ID NO: 95 (pg. 20, Table 1B), which is 96.5% identical to instant SEQ ID NO: 20. See alignment:
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The difference between Nager’s SEQ ID NO: 95 and the instantly claimed sequence is that Nager’s SEQ ID NO: 95 does not include the last two amino acid residues (positions 61-62) of instant SEQ ID NO: 20. However, Rajpal discloses the N-terminal flanking regions of immunoreceptor tyrosine-based inhibitory motif- (ITIM-) containing intracellular domains for naturally-occurring receptors, including G-CSFR according to SEQ ID NO: 350 (Table 3, pg. 43). Rajpal’s SEQ ID NO: 350 is a sequence comprising the amino acid sequence according to instant SEQ ID NO: 20, as instantly claimed. See alignment:
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Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the invention of Greenberg and Nager combined such that the G-CSFR domain comprises the amino acid sequence of instant SEQ ID NO: 20, as found in Rajpal, with a reasonable expectation of success because the claimed sequence corresponds to the known, naturally-occurring sequence of G-CSFR, and therefore this sequence would have been suitable to construct the chimeric receptor of the prior art references.
(c) Nager discloses that the “tyrosine effector domain” (cytotail domain) of IL-2Rβ comprises the amino acid sequence according to SEQ ID NO: 135 (pg. 21, Table 1B), which comprises the amino acid sequence according to instant SEQ ID NO: 21. See alignment:
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Transitional Phrases:
Claim 57 recites a chimeric receptor “comprising” (1) a G-CSFR ECD and (2) a second domain “comprising” (i) a G-CSFR transmembrane domain “consisting of” the amino acid sequence of SEQ ID NO: 8, (ii) a G-CSFR Box 1 and Box 2 region “consisting of” the amino acid sequence of SEQ ID NO: 20 and (iii) an IL-2Rβ ICD “consisting of” the amino acid sequence of SEQ ID NO: 21.
As instructed by MPEP 2111.03, the transitional phrases "comprising", "consisting essentially of" and "consisting of" define the scope of a claim with respect to what unrecited additional components or steps, if any, are excluded from the scope of the claim. The determination of what is or is not excluded by a transitional phrase must be made on a case-by-case basis in light of the facts of each case.
The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004) ("[L]ike the term ‘comprising,’ the terms ‘containing’ and ‘mixture’ are open-ended."). Invitrogen Corp. v. Biocrest Manufacturing, L.P., 327 F.3d 1364, 1368, 66 USPQ2d 1631, 1634 (Fed. Cir. 2003) ("The transition ‘comprising’ in a method claim indicates that the claim is open-ended and allows for additional steps."); Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997) ("Comprising" is a term of art used in claim language which means that the named elements are essential, but other elements may be added and still form a construct within the scope of the claim.); Moleculon Research Corp. v. CBS, Inc., 793 F.2d 1261, 229 USPQ 805 (Fed. Cir. 1986); In re Baxter, 656 F.2d 679, 686, 210 USPQ 795, 803 (CCPA 1981); Ex parte Davis, 80 USPQ 448, 450 (Bd. App. 1948) ("comprising" leaves "the claim open for the inclusion of unspecified ingredients even in major amounts"). In Gillette Co. v. Energizer Holdings Inc., 405 F.3d 1367, 1371-73, 74 USPQ2d 1586, 1589-91 (Fed. Cir. 2005), the court held that a claim to "a safety razor blade unit comprising a guard, a cap, and a group of first, second, and third blades" encompasses razors with more than three blades because the transitional phrase "comprising" in the preamble and the phrase "group of" are presumptively open-ended. "The word ‘comprising’ transitioning from the preamble to the body signals that the entire claim is presumptively open-ended." Id.
The transitional phrase "consisting of" excludes any element, step, or ingredient not specified in the claim. In re Gray, 53 F.2d 520, 11 USPQ 255 (CCPA 1931); Ex parte Davis, 80 USPQ 448, 450 (Bd. App. 1948) ("consisting of" defined as "closing the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith"). However, the "consisting of" phrase limits only the element set forth in that clause; other elements are not excluded from the claim as a whole. Mannesmann Demag Corp. v. Engineered Metal Products Co., 793 F.2d 1279, 230 USPQ 45 (Fed. Cir. 1986). See also In re Crish, 393 F.3d 1253, 73 USPQ2d 1364 (Fed. Cir. 2004) (The claims at issue "related to purified DNA molecules having promoter activity for the human involucrin gene (hINV)." Id., 73 USPQ2d at 1365. In determining the scope of applicant’s claims directed to "a purified oligonucleotide comprising at least a portion of the nucleotide sequence of SEQ ID NO:1 wherein said portion consists of the nucleotide sequence from … to 2473 of SEQ ID NO:1, and wherein said portion of the nucleotide sequence of SEQ ID NO:1 has promoter activity," the court stated that the use of "consists" in the body of the claims did not limit the open-ended "comprising" language in the claims (emphases added). Id. at 1257, 73 USPQ2d at 1367. The court held that the claimed promoter sequence designated as SEQ ID NO:1 was obtained by sequencing the same prior art plasmid and was therefore anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. Id. at 1256 and 1259, 73 USPQ2d at 1366 and 1369. The court affirmed the Board’s interpretation that the transition phrase "consists" did not limit the claims to only the recited numbered nucleotide sequences of SEQ ID NO:1 and that "the transition language ‘comprising’ allowed the claims to cover the entire involucrin gene plus other portions of the plasmid, as long as the gene contained the specific portions of SEQ ID NO:1 recited by the claim[s]." Id. at 1256, 73 USPQ2d at 1366.).
In this case, the transitional phrase “comprising” is used to describe the scope of the claimed chimeric receptor and the second domain. The transitional phrase “consisting of” is only used in the body of the claim to describe the scope of the transmembrane, Box 1 and 2, and ICD regions. Accordingly, the “consisting of” language only limits those elements set forth in the body of the claim, but other elements are not excluded from the claim as a whole. Moreover, the “comprising” language is used to describe the scope of the claimed invention as a whole, and, consequently, the scope of the claimed invention is inclusive or open-ended and may include additional, unrecited elements. Therefore, the use of “consisting of” in the body of the claim does not limit the open-ended “comprising” language of the claims, and the claimed chimeric receptor and the second domain may broadly contain additional, unrecited amino acid sequences. For these reasons, since the prior art contains at least the specific portions of the claimed chimeric receptor and the second domain (i.e., the amino acid sequences according to SEQ ID NOs: 8, 20-21), the use of “consisting of” in the body of the claim is not found to patentably distinguish the instantly claimed invention from the prior art.
For these reasons, claim 57 would have been prima facie obvious over the prior art.
Dependent claims:
Regarding claim 58, Greenburg discloses that G-CSFR undergoes homodimerization (pg. 11, ll. 27-29) and induces cellular proliferation upon activation by binding of its ligand, G-CSF (pg. 5, ll. 12-18; pg. 25, ll. 12-23; claim 17). Nager discloses that the chimeric receptors undergo dimerization (par. 20, 220, 223, 486) and induces proliferation, persistence, STAT activation, cytotoxicity upon activation by binding of its ligand (par. 52-57).
Regarding claims 60-62, Greenberg discloses expression of the chimeric receptor in lymphocytes, such as T cells and B cells. See, e.g., Abstract; pg. 4, ll. 30-33; pg. 7, ll. 29-32. Greenberg further discloses that cytotoxic T cells can be isolated from cancer patients (pg. 2, ll. 31-34), which reads on primary cells. Nager discloses expression of the chimeric receptor in immune cells, such as T cells, B cells, NK cells, NKT cells, macrophages, and dendritic cells. The immune cell may also be derived from a stem cell. See, e.g., Abstract; par. 42, 186. Nager further discloses that the cells may be obtained from a number of sources, including peripheral blood, of the subject (par. 293), which reads on primary cells.
Regarding claims 63, 69-72, Greenburg discloses that the chimeric receptor is encoded by a retroviral vector or a plasmid, and introduced into a host cell. See, e.g., pg. 8, ll. 24-28; pg. 9, ll. 4-10; pg. 14-17. Nager discloses that the chimeric receptor is encoded by a plasmid, lentivirus, retrovirus or adenovirus, and introduced into a host cell. See, e.g., par. 189, 317, 321.
Regarding claim 76, Nager discloses “kits” comprising one or more containers comprising an isolated immune cells comprising one or more polynucleotides encoding the chimeric cytokine receptor, and instructions for use. See, e.g., par. 339-342.
Claim 64 is rejected under 35 U.S.C. 103 as being unpatentable Greenberg, Nager, and Rajpal, as applied to claims 57-58, 60-63, 69-72, and 76 above; in further view of WO 2005/072340 A2 to Ayalon-Soffer et al.
This rejection is newly applied, necessitated by amendment.
Regarding claim 64, the claim recites that the extracellular domain (ECD) of G-CSFR comprises the amino acid sequence set forth in SEQ ID NO: 5. This limitation is not taught by Greenberg, Nager, and Rajpal.
Prior to the effective filing date of the instantly claimed invention, Ayalon-Soffer provides an amino acid sequence for wild-type, human G-CSFR according to SEQ ID NO: 183. See, e.g., Fig. 106. This sequence comprises the amino acid sequence of instant SEQ ID NO: 5, as instantly claimed. See alignment:
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Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the invention of Greenberg such that the G-CSFR domain comprises the amino acid sequence of instant SEQ ID NO: 5, as found in Ayalon-Soffer, with a reasonable expectation of success because the claimed sequence corresponds to the known, wild-type sequence of human G-CSFR, and therefore this sequence would have been suitable to construct Greenberg’s chimeric receptor comprising the ECD of G-CSFR. In addition, the use of the transitional phrase “consists of” in the body of the claim is not found to patentably distinguish the instantly claimed invention from the prior art for the same reasons provided above for claim 57.
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.
Claims 57-58, 60, 63, 69, 71-72, and 76 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 18/286,045 (reference to claim listing filed 04/02/2024). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the instant claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
This rejection is newly applied, necessitated by amendment.
The copending claims a chimeric receptor comprising an extracellular domain (ECD) of G-CSFR, a transmembrane domain (TMD) of G-CSFR, and an intracellular domain (ICD) comprising at least one signaling molecule binding site from an ICD of a cytokine receptor; wherein the at least one signaling molecule binding site is a SHC binding site and/or STAT5 binding site of IL-2Rβ; wherein the ICD of the chimeric receptor further comprises at least one Box 1 and Box 2 region of G-CSFR. See, e.g., claims 311, 314.
The copending claims further recite that the TMD comprises a sequence set forth in SEQ ID NO: 88. See, e.g., claim 314. This sequence is identical to instant SEQ ID NO: 8. See alignment:
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The copending claims further recite that the ICD comprises an amino acid sequence of SEQ ID NO: 90. See, e.g., claim 314. This sequence is identical to instant SEQ ID NO: 20. See alignment:
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The copending claims further recite that the ICD comprises an amino acid sequence of SEQ ID NO: 91. See, e.g., claim 314. This sequence is identical to instant SEQ ID NO: 21. See alignment:
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The copending claims further recite that the activated form of the chimeric receptor forms a homodimer, and, optionally, activation of the chimeric receptor causes a cellular response comprising at least one of proliferation, viability, persistence, cytotoxicity, cytokine secretion, memory, and enhanced activity of a cell expressing the receptor, and, optionally, the chimeric receptor is activated upon contact with a G-CSF (claim 312). Therefore, the limitation of instant claim 57 “wherein the chimeric receptor homodimerizes upon contact with G-CSF” is met by the copending claims.
For these reasons, instant claim 57 is anticipated by the copending claims.
Regarding instant claim 58, the copending claims recite that the activated form of the chimeric receptor forms a homodimer, and, optionally, activation of the chimeric receptor causes a cellular response comprising at least one of proliferation, viability, persistence, cytotoxicity, cytokine secretion, memory, and enhanced activity of a cell expressing the receptor, and, optionally, the chimeric receptor is activated upon contact with a G-CSF (claim 312). Further, the G-CSF is a wild-type G-CSF, and the extracellular domain of the G-CSFR is a wild-type extracellular domain (claim 313).
Regarding instant claims 60, 63, 69, 71-72, the copending claims further recite a nucleic acid encoding the chimeric receptor (claims 320), and a vector comprising thereof (claim 321), and expression vectors comprising thereof (claims 319-321). The chimeric receptor is also expressed in a cell, preferably an immune cell (claims 314 and 316).
Regarding instant claim 76, the copending claims recite a “kit” comprising cells, preferably immune cells, comprising one or more chimeric receptors, or one or more expression vectors encoding thereof, instructions for use, and at least one cytokine that binds the chimeric receptor, or one or more expression vectors encoding thereof (claim 319).
Claims 61-62 and 70 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 18/286,045 (reference to claim listing filed 04/02/2024), as applied to claims 57-58, 60, 63, 69, 71-72, and 76 above; in view of WO 94/22914 to Greenberg et al. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been prima facie obvious over the copending claims and secondary references. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
This rejection is newly applied, necessitated by amendment.
The teachings of Greenberg have been discussed above.
The copending claims recite the chimeric receptor is expressed in a cell, preferably an immune cell. See, e.g., claims 314 and 316. The copending claims do not recite that the immune cell is a T cell, an NK cell, an NKT cell, a B cell, a plasma cell, a macrophage, or a dendritic cell, as instantly claimed in claim 61.
However, Greenberg discloses expression of the chimeric receptor in lymphocytes, such as T cells and B cells. See, e.g., Abstract; pg. 4, ll. 30-33; pg. 7, ll. 29-32. Such cells are useful for treating cancer. See, e.g., pg. 2, ll. 28-35; pg. 16, ll. 23-34; pg. 17, ll. 10-21.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the invention of the copending claims by selecting a T cell, as found in Greensburg, with a reasonable expectation of success because the copending claims (e.g., claim 318) recites treating a cancer in a subject by administration of an immune cell expressing the chimeric receptor, and T cells were known in the art as therapeutically useful cell types for treating cancer in a subject, as suggested by Greenberg.
Regarding instant claim 62, Greenberg further discloses that T cells can be isolated from cancer patients (pg. 2, ll. 31-34), which reads on primary cells.
Regarding instant claim 70, Greenburg discloses that the chimeric receptor is encoded by a retroviral vector or a plasmid for introduction into a T cell. See, e.g., pg. 8, ll. 24-28; pg. 9, ll. 4-10; pg. 14-17.
Claim 64 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 18/286,045 (reference to claim listing filed 04/02/2024), as applied to claims 57-58, 60, 63, 69, 71-72, and 76 above; in view of WO 2005/072340 A2 to Ayalon-Soffer et al. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been prima facie obvious over the copending claims and secondary references. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
This rejection is newly applied, necessitated by amendment.
Regarding instant claims 64, the claim recites that the extracellular domain (ECD) of G-CSFR comprises the amino acid sequence set forth in SEQ ID NO: 5. The copending claims do not recite this limitation.
Prior to the effective filing date of the instantly claimed invention, Ayalon-Soffer provides an amino acid sequence for wild-type, human G-CSFR according to SEQ ID NO: 183. See, e.g., Fig. 106. This sequence comprises the amino acid sequence of instant SEQ ID NO: 5, as instantly claimed. See alignment, provided above.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the invention of the copending claims such that the G-CSFR domain comprises the amino acid sequence of instant SEQ ID NO: 5, as found in Ayalon-Soffer, with a reasonable expectation of success because the instantly claimed sequence corresponds to the known, wild-type sequence of human G-CSFR, and therefore this sequence would have been suitable to construct the chimeric receptor of the copending claims. In addition, the use of the transitional phrase “consists of” in the body of the claim is not found to patentably distinguish the instantly claimed invention from the cited references for the same reasons provided above for claim 57 under 35 U.S.C. 103.
Response to Arguments
Applicant’s remarks filed 06/22/2026 have been carefully considered, but are not found persuasive. In this case, applicant’s arguments rely on the amendment to the claims and use of “consisting of” language in the body of claim 57. This amendment has been addressed in the new grounds of rejection set forth above. The arguments regarding alleged unexpected results do not provide a comparison with the prior art, and the claimed homodimerization and intracellular signalling would have been expected properties from the prior art. See, the examiner’s response to arguments in the previous Office action mailed 03/23/2026. Regarding the double patenting rejection, the examiner acknowledges that, if a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, as instructed by MPEP 804. However, in this case, the provisional double patenting rejection is not the only rejection remaining in the application, and, therefore, the double patenting rejection is maintained.
Conclusion
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 JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James D Schultz can be reached at (571)272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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