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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 July 25, 2025 has been entered.
Status of Claims
Claims 30-34, 36-44, 47-48, 54-74, 76-77, 83-85, 94, 103, 112, 116, and 119-121 are currently pending. Claims 83-85, 94, 103, 112, 116, and 119-120 stand withdrawn from consideration pursuant to 37 CFR 1.142(b), there being no allowable generic or linking claim. Claims 30-34, 36-44, 47-48, 54-74, and 76-77 are under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
WITHDRAWN OBJECTIONS and/or REJECTIONS
Applicant’s arguments, see Remarks on pg. 22, filed July 25, 2025, with respect to all nonstatutory double patenting rejections over copending application No. 17/640,176 have been fully considered and are persuasive. The rejection of the instant claims on the grounds of nonstatutory double patenting over copending application No. 17/640,176 has been withdrawn.
Claim Rejections - 35 USC § 103
Claims 34, 40-41, 43-44, 47-48, 54, and 76 are rejected under 35 U.S.C. 103 as being unpatentable over Roberts et al. in US 5,712,149 published on Jan. 27, 1998 and Peterson et al. Nature. October, 29, 1987. 329: 842-846, as cited in the IDS; alone or as evidenced Posey et al. Mol Ther. May 2015. 23(Suppl. 1): S83 and Xu et al. Oncogene. April 14, 2014. 34:1520-1531, cited herewith.
Applicant's arguments filed July 25, 2025 have been fully considered but they are not persuasive.
Roberts teaches a base device, i.e. chimeric stimulatory receptor (CSR) comprising an extracellular domain of a cell surface differentiation antigen (col. 6, lines 59-60), a cytoplasmic region of CD2 (col. 7, lines 46-48) and transmembrane domain contributed by the domain of the protein contributing the cytoplasmic portion (col. 8, lines 15-17) and a signal sequence of the extracellular domain (col. 11, lines 12-15); additionally, the CSR contains a cytoplasmic domain of the CD3 zeta chain (col. 7, lines 61-65). Roberts teaches that the co-stimulatory chimeric receptors are useful for augmenting proliferation of lymphocyte host cells in vitro and in vivo (col. 5, lines 64-66). Roberts points the skilled artisan toward creating CSRs to support T cells “by permitting the use of ligands other than the natural ligand to provide the required co-stimulatory signal.” (col. 4, line 60 through col. 5 line 10).
Applicant argues replacing the CD4 extracellular domain of any construct disclosed in Example 4 goes against the explicit disclosure of Roberts (see Remarks pg. 10 in the last ¶ through the last ¶ on pg. 11 spanning pg. 12). “[T]he only disclosure of Roberts relating to a CD2 extracellular domain is found in Example 4, which discloses replacing either the entire CD2 extracellular domain… or the portion of the CD2 extracellular domain comprising the agonist binding regions[.]” (Remarks pg. 13 in the first full ¶). See also Remarks in the last ¶ on pg. 13 spanning pg. 14.
Examiner respectfully disagrees. In lines 59-60 of col. 6, Roberts teaches CSRs having extracellular domains including, but not limited to, cell surface differentiation antigens. Noted herein, CD2 is a “cell surface differentiation antigen.” Thus, CD2 falls within the explicitly stated genus of extracellular domains that Roberts considers. Replacing the CD4 domain of any construct of Example 4 does not go against the explicit disclosure of Roberts. Indeed, it would have been clear to the skilled artisan considering the entirety of Roberts that CD4 is merely an exemplary embodiment.
Peterson teaches a CD2 molecule comprising a mutated extracellular domain that ablates CD58 (aka LFA-2) and binds agonistic antibodies. See Office Action mailed on July 19, 2024 in the last ¶ on pg. 19 spanning pg. 20 for a detailed discussion.
Roberts differs from the instant claims because Roberts does not disclose that the extracellular domain of the CSR is a CD2 extracellular domain to which an agonist binds comprising a mutation or truncation that ablates binding of human CD2 to CD58. Peterson teaches a CD2 molecule with an extracellular domain to which an agonist binds comprising a mutation that ablates binding of human CD2 to CD58, but differs from the instant invention by the CD3zeta signal transduction domain.
Roberts does not explicitly suggest using an extracellular domain derived from CD2 and Peterson does not explicitly suggest constructing a CSR. Applicants argue that there was no motivation to combine the references’ teachings to construct a CSR of Roberts using the CD2 extracellular domain of Peterson that binds an agonist but not CD58 because no such explicit suggestion was made. (Remarks, e.g., pg. 13, last full ¶). However, the courts have repeatedly held that the rationale to modify or combine prior art does not have to be explicitly suggested.
“The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992); see also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); Ex parte Clapp, 227 USPQ 972 (Bd. Pat. App. & Inter. 1985) (examiner must present convincing line of reasoning supporting rejection); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning).” (see MPEP 2144. I.).
Examiner submits there were clear design incentives that would have motivated the skilled artisan to arrive at the instantly claimed invention implied by the applied art and/or found in the knowledge generally available to one or ordinary skill in the art.
Firstly, Roberts provides explicit motivation to produce CSRs having non-natural extracellular domain for the purpose of inducing T cell expansion and/or activation in vitro and/or in vivo. Indeed, Roberts even suggests there are situations where making a CSR more manipulatable is desirable, e.g. if the natural ligand is missing or less useful. Making a CSR more manipulatable for the purpose of expanding T cell populations, even in the absence teaching specific situations in which the natural ligand for CD2 is missing or less useful, provides incentive enough to have motivated the person of ordinary skill in the art to use the mutated CD2 extracellular domain of Peterson in a CSR of Roberts. Indeed, the skilled artisan would have recognized that using the extracellular domain of Peterson was advantageous over the CD4 extracellular domain of Robert’s exemplary embodiments, because using CD4 would not allow complete control of stimulation of the CSR since the natural ligand for CD4 could stimulate the CD4 CSR in vivo. However, it would have been apparent to the skilled artisan that using a mutated CD2 extracellular domain that only activates in response to the addition of agonistic antibodies provides a more manipulatable and controlled activation of T cells through the CSR.
Additionally, chimeric antigen receptors bearing a CD2 co-stimulatory domain combined with a CD3zeta activation domain (SS1CD2z) have a “fast and durable anti-tumor response… while both SS128z [comprising a CD28 co-stimulatory domain] and SS1BBz [comprising a 4-1BB co-stimulatory domain] T cells lagged in terms of response rate.” See Posey. Thus, Posey teaches toward selecting the CD2 co-stimulatory domain and combining said CD2 domain with a CD3zeta signaling / activation domain for the CSR of Roberts. Indeed, Posey teaches that CD2z constructs can provide functional domains that achieve Roberts’ intended use, activation and proliferation of lymphocytes.
Applicant further argues the proposed modification renders the prior art unsatisfactory for its intended purpose because “replacing the CD4 extracellular domain with a CD2 activation component… [would require] two separate agonists (i.e., a CD4 agonist and a CD2 agonist, respectively)… to activate the primary activation signal and the co-stimulatory signal.” (see Remarks on pg. 12 in the first full ¶).
Again, Examiner respectfully disagrees. The cited portion of Roberts, col. 8 lines 11-14, are preceded by a discussion regarding joining the cytoplasmic domain of CD3 zeta to provide a primary activation signal simultaneously with a CD28 co-stimulatory signal upon CD4 extracellular domain ligation. In the described, exemplary construct comprising a CD4 extracellular, a CD28 co-stimulatory domain, and a CD3 zeta activation domain, a single ligand / agonist for CD4, e.g. gp120, stimulates the co-stimulatory and activation signal because the receptor comprises the intracellular domain for each. The modification set forth in the prima facie case is the use of Peterson’s mutated CD2 extracellular domain and a CD2 co-stimulatory domain in combination with a CD3 zeta activation domain. As an analogous to structure Robert’s described / exemplary embodiments, the person of ordinary skill in the art would have recognized that only a CD2 agonist would be necessary to provide co-stimulatory signal and primary activation signal simultaneously, because the CSR construct of Roberts in view of Peterson has the intracellular domains for both signals to be induced upon an agonizing event to the CD2 extracellular domain. Applicant believes that a skilled artisan would have needed a CD4 and CD2 agonist to induce said simultaneous signal in the CSR of Roberts in view of Peterson. However, there is no evidence to this effect. It would be unclear to the skilled artisan how an anti-CD4 agonist would be needed when the CSR of Roberts in view of Peterson as set forth in the prima facie case lacks any part of a CD4 molecule. Therefore, when Applicants’ arguments are weighed against the objective evidence of record, the prima facie case stands because the skilled artisan would have had the expectation that the CSR of Roberts in view of Peterson does, in fact, function for its intended purpose as described above.
That said, Applicant argues the applied art “does not teach or suggest that a CD2 extracellular domain that both binds to an agonist and does not bind to CD58 would provide any benefit in a CSL” because no specific situations in which the natural CD2 ligand (i.e. CD58) is missing or less useful are pointed to in the applied art. (Remarks on pg. 12 in the last ¶ spanning pg. 13 and pg. 14 in the first full ¶). Notwithstanding the sufficient motivation to combine set forth above and solely arguendo, CD58 is highly expressed on colorectal tumor initiating cells (CT-ICs) (see Xu pg. 1521 and Fig. 1 and Fig. 2, particularly Fig. 2b). Stimulation of CD58 by lymphocytes, agonistic antibody, or recombinant CD2 upregulates the Wnt signaling pathway, which plays a role in cell renewal (see pg. 1524 in the second col. and Fig. 5 on pg. 1526). Xu evidences that CD58 is less useful in CD58 positive colorectal cancer because lymphocytes bearing a natural CD2 ectodomain can stimulate Wnt signaling through CD58 thereby promoting cancer cell persistence. Thus, the ability to manipulate T cell proliferation and activation solely through the agonistic antibodies taught by Peterson would provide the skilled artisan with an advantage in the context of, e.g., CD58+ colorectal cancer. By using the CD2 extracellular domain taught by Peterson one of ordinary skill would have recognized the advantage of avoiding the promotion of cancer cells’ survival through lymphocyte CD2-CD58 mediated stimulation, while still allowing control over T cell proliferation and activation through the use of anti-CD2 antibodies.
In conclusion, when Applicant’s arguments are taken as a whole and weighed against the evidence supporting the prima facie case of unpatentability, the instant claims, by a preponderance of evidence, remain unpatentable. See M.P.E.P. § 716.01(d).
Claims 30-33, 34, 36-41, 43-44, 47-48, 54, and 76 stand and claim 121 is rejected under 35 U.S.C. 103 as being unpatentable over Roberts et al. in US 5,712,149 published on Jan. 27, 1998 and Peterson et al. Nature. October 29, 1987. 329: 842-846, as cited in the IDS; alone or evidenced by Posey et al. Mol Ther. May 2015. 23(Suppl. 1): S83 and Xu et al. Oncogene. April 14, 2014. 34:1520-1531, cited herewith; as applied to claim 34, 40-41, 43-44, 47-48, 54, and 76 above and further in view of UniProt. P06729 CD2_Human. CD2 sequence history at Aug. 30, 2017 retrieved from the Internet on July 9, 2024 from <URL: https://www.uniprot.org/uniprotkb/P06729/history> and Pule et al. in WO 2016/030691 published on Mar. 3, 2016.
Roberts and Peterson in view of UniProt teach a D111H mutation (see Office Action mailed July 19, 2024 on pgs. 22-24). Thus, claim 121 is rejected over the applied art for the reasons made of record.
Applicant's arguments filed July 25, 2025 have been fully considered but they are not persuasive.
Applicant argues that Roberts in view of Peterson only teaches replacing a CD2 extracellular domain with CD4, thereby teaching away from the instantly claimed CSR and lacking motivation to combine (see pg. 15 in the first full ¶). To the contrary, as demonstrated above, Roberts teaches an extracellular domain of a cell surface differentiation antigen (col. 6, lines 59-60), wherein CD4 is merely an exemplary embodiment. Neither Roberts nor Peterson “criticize, discredit or otherwise discouraged the solution claimed.” See MPEP 2123 II. “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).” Moreover, making a CSR of Roberts more manipulatable is an implicit design incentive which would have motivated the skilled artisan to use the mutated CD2 extracellular domain of Peterson as discussed above. Thus, Applicants’ argument that Uniprot and/or Pule do not provide motivation is obviated in view of the foregoing (see Remarks on pg. 15in the penultimate ¶ through pg. 16 in the first full ¶).
In conclusion, when Applicant’s arguments are taken as a whole and weighed against the evidence supporting the prima facie case of unpatentability, the instant claims, by a preponderance of evidence, remain unpatentable. See M.P.E.P. § 716.01(d).
Claims 34, 40-44, 47-48, 54, and 76 stand rejected under 35 U.S.C. 103 as being unpatentable over Roberts et al. in US 5,712,149 published on Jan. 27, 1998 and Peterson et al. Nature. October 29, 1987. 329: 842-846, as cited in the IDS; alone or as evidenced by Posey et al. Mol Ther. May 2015. 23(Suppl. 1): S83 and Xu et al. Oncogene. April 14, 2014. 34:1520-1531, cited herewith; as applied to claim 34, 40-41, 43-44, 47-48, 54, and 76 above and further in view of Cooper et al. in US 2016/0158285 A1 published on Jun. 9, 2016.
Applicant's arguments filed July 25, 2025 have been fully considered but they are not persuasive.
Applicant argues that Roberts in view of Peterson only teaches replacing a CD2 extracellular domain with CD4, thereby teaching away from the instantly claimed CSR and lacking motivation to combine (see pg. 16 in the last ¶ spanning pg. 17). To the contrary, as demonstrated above, Roberts teaches an extracellular domain of a cell surface differentiation antigen (col. 6, lines 59-60), wherein CD4 is merely an exemplary embodiment. Neither Roberts nor Peterson “criticize, discredit or otherwise discouraged the solution claimed.” See MPEP 2123 II. “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).” Moreover, making a CSR of Roberts more manipulatable is an implicit design incentive which would have motivated the skilled artisan to use the mutated CD2 extracellular domain of Peterson as discussed above. Thus, Applicants’ argument that Cooper does not provide motivation is obviated in view of the foregoing (see Remarks on pg. 17 in the first full ¶).
Claims 34, 40-41, 43-44, 47-48, 54-61, 64-73, and 76-77 stand rejected under 35 U.S.C. 103 as being unpatentable over Roberts et al. in US 5,712,149 published on Jan. 27, 1998 and Peterson et al. Nature. October 29, 1987. 329: 842-846, as cited in the IDS; alone or as evidenced by Posey et al. Mol Ther. May 2015. 23(Suppl. 1): S83 and Xu et al. Oncogene. April 14, 2014. 34:1520-1531, cited herewith; as applied to instant claim 34, 40-41, 43-44, 47-48, 54, and 76 above, and further in view of Conway et al. in US 2019/0048060 published Feb. 14, 2019 and effectively filed on 62/542,511.
Applicant's arguments filed July 25, 2025 have been fully considered but they are not persuasive.
Applicant argues that Roberts in view of Peterson only teaches replacing a CD2 extracellular domain with CD4, thereby teaching away from the instantly claimed CSR and lacking motivation to combine (see pg. 17 in the last ¶ through pg. 18 in the first full ¶). To the contrary, as demonstrated above, Roberts teaches an extracellular domain of a cell surface differentiation antigen (col. 6, lines 59-60), wherein CD4 is merely an exemplary embodiment. Neither Roberts nor Peterson “criticize, discredit or otherwise discouraged the solution claimed.” See MPEP 2123 II. “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).” Moreover, making a CSR of Roberts more manipulatable is an implicit design incentive which would have motivated the skilled artisan to use the mutated CD2 extracellular domain of Peterson as discussed above. Thus, Applicants’ argument that Conway does not provide motivation is obviated in view of the foregoing (see Remarks on pg. 18 in the second full ¶).
Claims 34, 40-41, 43-44, 47-48, 54-73, and 76-77 stand rejected under 35 U.S.C. 103 as being unpatentable over Roberts et al. in US 5,712,149 published on Jan. 27, 1998 and Peterson et al. Nature. October, 29, 1987. 329: 842-846, as cited in the IDS; alone or as evidenced by Posey et al. Mol Ther. May 2015. 23(Suppl. 1): S83 and Xu et al. Oncogene. April 14, 2014. 34:1520-1531, cited herewith; in view of Conway et al. in US 2019/0048060 published Feb. 14, 2019 and effectively filed on 62/542,511; as applied to instant claims 34, 40-41, 43-44, 47-48, 54-61, 64-73, and 76-77 above, and further in view of Gornalusse et al. Nature Biotech. Aug. 2017. 35(8):765-772.
Applicant's arguments filed July 25, 2025 have been fully considered but they are not persuasive.
Applicant argues that Roberts in view of Peterson only teaches replacing a CD2 extracellular domain with CD4, thereby teaching away from the instantly claimed CSR and lacking motivation to combine (see pg. 18 in the last ¶ through pg. 19 in the first full ¶). To the contrary, as demonstrated above, Roberts teaches an extracellular domain of a cell surface differentiation antigen (col. 6, lines 59-60), wherein CD4 is merely an exemplary embodiment. Neither Roberts nor Peterson “criticize, discredit or otherwise discouraged the solution claimed.” See MPEP 2123 II. “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).” Moreover, making a CSR of Roberts more manipulatable is an implicit design incentive which would have motivated the skilled artisan to use the mutated CD2 extracellular domain of Peterson as discussed above. Thus, Applicants’ argument that Gornalusse does not provide motivation is obviated in view of the foregoing (see Remarks on pg. 19 in the penultimate ¶).
Claims 34, 40-41, 43-44, 47-48, 54-61, 64-74, and 76-77 stand rejected under 35 U.S.C. 103 as being unpatentable over Roberts et al. in US 5,712,149 published on Jan. 27, 1998 and Peterson et al. Nature. October 29, 1987. 329: 842-846, as cited in the IDS; ; alone or as evidenced by Posey et al. Mol Ther. May 2015. 23(Suppl. 1): S83 and Xu et al. Oncogene. April 14, 2014. 34:1520-1531, cited herewith; in view of Conway et al. in US 2019/0048060 published Feb. 14, 2019 and effectively filed on 62/542,511; as applied to instant claims 34, 40-41, 43-44, 47-48, 54-61, 64-73, and 76-77 above, and further in view of Oda et al. in WO 2018/170475 A1 published on Sept. 20, 2018 and effectively filed on March 17, 2017.
Applicant's arguments filed July 25, 2025 have been fully considered but they are not persuasive.
Applicant argues that Roberts in view of Peterson only teaches replacing a CD2 extracellular domain with CD4, thereby teaching away from the instantly claimed CSR and lacking motivation to combine (see pg. 20 in the first and second ¶). To the contrary, as demonstrated above, Roberts teaches an extracellular domain of a cell surface differentiation antigen (col. 6, lines 59-60), wherein CD4 is merely an exemplary embodiment. Neither Roberts nor Peterson “criticize, discredit or otherwise discouraged the solution claimed.” See MPEP 2123 II. “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).”
Applicant argues that there is no motivation to combine Roberts with Oda because “replacing the Roberts CD4 extracellular domain with a CD2 extracellular domain would be contrary to the intended purpose stated in Roberts” since stimulation of Roberts’ exemplary embodiment results in a primary activation and co-stimulatory signal simultaneously. As discussed on pg. 6 in the last ¶ spanning pg. 7 of this Office Action, only a CD2 agonist would be necessary to provide co-stimulatory signal and primary activation signal simultaneously, and it would be unclear to the skilled artisan how an anti-CD4 agonist would be needed when the CSR of Roberts in view of Peterson as set forth in the prima facie case lacks any part of a CD4 molecule.
Applicant argues that Oda’s teachings regarding CD58 as a target to which the inventive fusion protein binds (e.g. Oda at pg. 58 in lines 18-28), makes CD58 a desirable target to use for the CSR of Roberts in view of Peterson and Conway (Remarks pg. 21 in the first ¶). Examiner respectfully submits that Oda’s teaching on stimulating a fusion protein with CD58 does not discourage or discredit the claimed invention as would be obvious over Roberts in view of Peterson and Conway. Moreover, Xu evidences that in treating CD58+ colorectal cancer, one of ordinary skill would not have desired to retain CD58 binding as Applicant suggests because doing so would have promoted cancer cell survival.
Moreover, making a CSR of Roberts more manipulatable is an implicit design incentive which would have motivated the skilled artisan to use the mutated CD2 extracellular domain of Peterson as discussed above. Thus, Applicants’ argument that there was no motivation to combine references is obviated in view of the foregoing.
Double Patenting
Claims 30-34 and 40 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-11, 15-16, 19-21, 24-27, 31, 32, 35, 37-38, and 40-42 of copending Application No. 17/906,034 (reference application) and Roberts et al. in WO 96/23814 A1 published on August 8, 1996; as evidenced by Posey et al. Mol Ther. May 2015. 23(Suppl. 1): S83.
Claims 30-34, 40-44, 47, 54 and 76 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-41 of copending Application No. 17/906,034 and Roberts et al. in WO 96/23814 A1 published on August 8, 1996; as evidenced by Posey et al. Mol Ther. May 2015. 23(Suppl. 1): S83 as applied to instant claim 34 above and further in view of Cooper et al. in US 2016/0158285 A1 published on Jun. 9, 2016.
Claims 30-34, 40-44, 47-48, 55-61, 64-73, and 76-77 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-41 of copending Application No. 17/906,034 and Roberts et al. in WO 96/23814 A1 published on August 8, 1996; as evidenced by Posey et al. Mol Ther. May 2015. 23(Suppl. 1): S83 as applied to instant claim 34 above and further in view of Conway et al. in US 2019/0048060 published Feb. 14, 2019 and effectively filed on 62/542,511.
Applicant's arguments filed July 25, 2025 have been fully considered but they are not persuasive.
Applicant argues that ‘034’s construct “excludes the claimed construct comprising a CD2 cytoplasmic domain” because ‘034’s CSR comprises a TNFR2 (see pg. 23 in the last ¶ spanning pg. 24). Examiner respectfully disagrees. ‘034 does not exclude a CSR comprising a CD2 cytoplasmic domain. The claims of ‘034 use open claim language “comprising” allowing for additional elements beyond the recited TNFR2 intracellular domain. Thus, the scope of ‘034 includes constructs comprising, e.g. TNFR2 and CD2 intracellular domains.
Applicant argues that using a CD2 intracellular domain would alter the intended purpose of a CSR comprising a TNFR2 domain, which is to “control Treg proliferation, differentiation and ultimately stability and longevity.” Applicant contrast CD2 function by stating that CD2 is a co-stimulatory receptor involved in the activation of T cells and cytokine secretion, such as IL-2. See Remarks on pg. 24 in the first full ¶. However, Roberts also teaches that CSRs, e.g. those comprising any of the intracellular domains disclosed including CD2, promotes T cell proliferation, differentiation, and/or maturation (see col. 7 in lines 1-8). Roberts is generic as to the species of T cell in which the CSR is expressed and the skilled artisan would have known at the time of instant filing that CD2 stimuli is “mandatory for Treg cell survival.” (Kashiwakura et al. 2012. Immunology. 139:48-60, cited herewith; see Abstract). Thus, the combination of ‘034 and Roberts supports the intended purpose of ‘034 rather than altering it as Applicant alleges.
In conclusion, when Applicant’s arguments are taken as a whole and weighed against the evidence supporting the prima facie case of unpatentability, the instant claims, by a preponderance of evidence, remain unpatentable. See M.P.E.P. § 716.01(d).
Conclusion
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/B.K.S./Examiner, Art Unit 1644
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683