DETAILED 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 .
Status of the Claims
Applicant’s submission filed 24 November has been entered. Claims 1-6, 8, 10-15, 32-37, 53, and 59-62 are pending. Claims 1, 5-6, and 14 have been amended, while claims 18 and 21 have been cancelled without prejudice or disclaimer and claim 62 has been newly added. Therefore, prosecution on the merits continues for claims 1-6, 8, 10-15, and 60-61, with claims 32-37, 53, 59, and 62 withdrawn as being drawn to a non-elected species or invention. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Objection of claims 5-6
Applicant’s amendments to each of claims 5 and 6 correct the minor typographical errors and thus obviate the objections of record.
Therefore, the objections are withdrawn.
RE: Rejection of claims 1-2, 4, 8, 10-14, and 60 under 35 USC 103 over Valamehr et al in view of Blazar et al
Applicant has amended independent claim 1 to require, at least, the expression of CD47 to be sufficiently increased such that the release of interferon gamma by NK cells is reduced, as well as the hypoimmunogenic T cell to be CD8+CD45RA+CCR7-. As Applicant has narrowed the scope of a previously recited limitation and presented a new limitation that has previously not been considered, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s arguments are addressed in so far as they are applicable to the new rejection of record, which utilizes Valamehr et al:
Applicant has traversed the rejection, asserting in Pages 7-9 of the Remarks filed 24 November 2025 that Valamehr et al fail to teach a threshold increase of CD47 expression that results in the decreased interferon gamma secretion by natural killer cells. Applicant cites Example 3 of the instant Specification and to Deuse for support. In response, the Examiner respectfully submits that Example 3 of the instant Specification is directed to the co-culture of hypoimmunogenic induced pluripotent stem cells that are B2M-/-CIITA-/-CD47+ with natural killer cells, and the resulting interferon gamma secretion from those natural killer cells with or without a CD47 blockade. Applicant fails to teach a threshold expression of CD47 that led to the decreased interferon gamma secretion from the natural killer cells. Instead, the only potential reference to a threshold CD47 expression level within Applicant’s disclosure would be that the “hypoimmunogenic CAR-T cells have an increased expression of CD47 protein compared to a wild-type or native T cell”. See Paragraph [00181] of the instant Specification. However, Applicant fails to quantify the amount of CD47 expression necessary to decrease interferon secretion by the co-cultured natural killer cells. Furthermore, Applicant’s citations to Deuse within Page 9 of the Remarks filed 24 November 2025 do not explicitly disclose an amount of CD47 mRNA required by the HLA-deficient hiEC cells to diminish interferon gamma secretion by co-cultured natural killer cells, instead stating that the two HLA-deficient hiEC cell clones that expressed CD47 at a level greater than the average of the pooled cells were not killed by natural killer cells. It is also of note that both Applicant’s Example 3 and the citations from Deuse do not teach the effects of CD47 expression on a hypoimmunogenic T cell, as is claimed, since Applicant’s Example 3 is directed to hypoimmunogenic induced pluripotent stem cells and Deuse is directed to human intestinal epithelial cells. Therefore, since Valamehr et al teach that CD47 expression is increased compared to wildtype expression, which is the same “threshold” taught by the instant disclosure, the hypoimmunogenic T cells of Valamehr et al have the same structure and resulting effect as the cells of the instant claims.
With that, the Examiner notes that Applicant has argued on Page 12 of the Remarks filed 24 November 2025 that Valamehr et al only mention the increased expression of CD47 prophetically, and do not teach CD47 expression that is sufficient to reduce the release of interferon gamma by natural killer cells. However, the Examiner respectfully submits that the claims are to a composition (“A hypoimmunogenic T cell”) comprising several structural limitations, including as amended, wherein “CD47 expression is increased when compared to a wild-type T cell, wherein the increased CD47 expression is sufficient to reduce the release of interferon gamma (IFN-gamma) by NK cells when compared to a T cell … having CD47 expression that is not increased comprises to the wild type T cell….”, which appears to be a contingent limitation. See MPEP § 2111.04:
The broadest reasonable interpretation of a system (or apparatus or product) claim having structure that performs a function, which only needs to occur if a condition precedent is met, requires structure for performing the function should the condition occur. The system claim interpretation differs from a method claim interpretation because the claimed structure must be present in the system regardless of whether the condition is met and the function is actually performed.
And:
“when analyzing the claimed system as a whole, the PTAB determined that "[t]he broadest reasonable interpretation of a system claim having structure that performs a function, which only needs to occur if a condition precedent is met, still requires structure for performing the function should the condition occur." Schulhauser at 14. Therefore "[t]he Examiner did not need to present evidence of the obviousness of the [ ] method steps of claim 1 that are not required to be performed under a broadest reasonable interpretation of the claim (e.g., instances in which the electrocardiac signal data is not within the threshold electrocardiac criteria such that the condition precedent for the determining step and the remaining steps of claim 1 has not been met);" however to render the claimed system obvious, the prior art must teach the structure that performs the function of the contingent step along with the other recited claim limitations. Schulhauser at 9, 14.
As such, since the structure of the T cells as taught by Valamehr et al is equivalent to that of the instant claims, and there is no evidence to the contrary that the overexpression of CD47 on the hypoimmunogenic T cells as taught by Valamehr et al is capable of performing the contingent step of the claimed composition – see discussion above – a proper rejection need not render obvious the contingent step, contrary to Applicant’s arguments.
Applicant has further traversed the rejection, asserting in Pages 11-12 of the Remarks filed 24 November 2025 that Valamehr et al teach away from the reduced interferon gamma release from NK cells, as Example 15 of Valamehr et al shows the treatment of TAP2-/- cells with exogenous interferon gamma. In response, the Examiner respectfully submits that the instant claims are directed to a hypoimmunogenic T cell having an increased expression of CD47, wherein the increased CD47 expression results in a decrease of interferon gamma secretion by natural killer cells. Accordingly, the Examiner fails to see how Applicant concluded that treating cells with exogenous interferon gamma teaches away from the instant claim, as the instant claim only requires the increased CD47 expression within the hypoimmunogenic T cells to have a downstream effect of reducing peripheral NK cell interferon gamma secretion. It is also of note that the claims do not require the complete ablation of interferon gamma secretion, just a reduced amount of interferon gamma secretion. Therefore, Applicant’s arguments do not serve as sufficient evidence to discredit the teachings of Valamehr et al, as the reference itself must articulate and discredit the teaching. See MPEP § 2141.02(VI). Furthermore, the Examiner respectfully submits that Applicant is relying upon a single exemplary embodiment within the disclosure of Valamehr et al that shows an alternative method to create HLA class I deficient iPSCs, and is not relevant to the rejection of record. See MPEP § 2123 and MPEP § 2141.02.
It is of note that Applicant has provided arguments against withdrawn rejections in Pages 7-9 of the Remarks filed 24 November 2025. The Examiner respectfully submits that the rejection of record did not rely upon the principles of inherency, and instead was rendered obvious by a piece of prior art.
RE: Rejection of claims 1-6, 8, 10-15, and 60-61 under 35 USC 103 over Valamehr et al in view of Blazar et al and further in view of DiPersio et al
Applicant has amended independent claim 1 to require the expression of CD47 to be sufficiently increased such that the release of interferon gamma by NK cells is reduced, as well as the hypoimmunogenic T cell to be CD8+CD45RA+CCR7-. As Applicant has narrowed the scope of a previously recited limitation and presented a new limitation that has previously not been considered, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s arguments are addressed in so far as they are applicable to the new rejection of record, which utilizes Valamehr et al and DiPersio et al:
Applicant has traversed the rejection, asserting in Pages 10 and 14 of the Remarks filed 24 November 2025 that DiPersio et al fail to mention CD47 within their disclosure. In response, the Examiner respectfully submits that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the instant case, DiPersio et al was a tertiary reference relied upon to teach the domains and regions comprised within the CAR.
RE: Provisional rejection of claims 1-6, 8, 10-15, and 60-61 over claims 1-4 and 31 of copending Application No. 17/632,026 in view of Valamehr et al, Blazar et al, and DiPersio et al
Applicant has amended independent claim 1 to require the expression of CD47 to be sufficiently increased such that the release of interferon gamma by NK cells is reduced, as well as the hypoimmunogenic T cell to be CD8+CD45RA+CCR7-. As Applicant has narrowed the scope of a previously recited limitation and presented a new limitation that has previously not been considered, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s arguments are addressed in so far as they are applicable to the new rejection of record:
Applicant has requested in Pages 14-15 of the Remarks filed 24 November 2025 that the rejection be held in abeyance. In response, the Examiner respectfully reminds Applicant that 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. Applicant did not traverse the NSDP rejection.
RE: Provisional rejection of claims 1-6, 8, 10-15, and 60-61 over claims 1-3, 5, and 27 of copending Application No. 17/637,789 in view of Valamehr et al, Blazar et al, and DiPersio et al
Applicant has amended independent claim 1 to require the expression of CD47 to be sufficiently
increased such that the release of interferon gamma by NK cells is reduced, as well as the hypoimmunogenic T cell to be CD8+CD45RA+CCR7-. As Applicant has narrowed the scope of a previously recited limitation and presented a new limitation that has previously not been considered, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s arguments are addressed in so far as they are applicable to the new rejection of record:
Applicant has requested in Pages 14-15 of the Remarks filed 24 November 2025 that the rejection be held in abeyance. In response, the Examiner respectfully reminds Applicant that 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. Applicant did not traverse the NSDP rejection.
RE: Provisional rejection of claims 1-6, 8, 10-15, and 60-61 over claims 410, 413-415, and 421-422 of copending Application No. 18/682,782 in view of Valamehr et al, Blazar et al, and DiPersio et al
Applicant has amended independent claim 1 to require the expression of CD47 to be sufficiently increased such that the release of interferon gamma by NK cells is reduced, as well as the hypoimmunogenic T cell to be CD8+CD45RA+CCR7-. As Applicant has narrowed the scope of a previously recited limitation and presented a new limitation that has previously not been considered, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s arguments are addressed in so far as they are applicable to the new rejection of record:
Applicant has requested in Pages 14-15 of the Remarks filed 24 November 2025 that the rejection be held in abeyance. In response, the Examiner respectfully reminds Applicant that 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. Applicant did not traverse the NSDP rejection.
RE: Provisional rejection of claims 1-6, 8, 10-15, and 60-61 over claims 312, 314-315, 317, 325-326, and 328-329 of copending Application No. 18/021,036 in view of Valamehr et al, Blazar et al, and DiPersio et al
Applicant has amended independent claim 1 to require the expression of CD47 to be sufficiently increased such that the release of interferon gamma by NK cells is reduced, as well as the hypoimmunogenic T cell to be CD8+CD45RA+CCR7-. As Applicant has narrowed the scope of a previously recited limitation and presented a new limitation that has previously not been considered, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s arguments are addressed in so far as they are applicable to the new rejection of record:
Applicant has requested in Pages 14-15 of the Remarks filed 24 November 2025 that the rejection be held in abeyance. In response, the Examiner respectfully reminds Applicant that 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. Applicant did not traverse the NSDP rejection.
RE: Provisional rejection of claims 1-6, 8, 10-15, and 60-61 over claims 189, 198-199, and 205-209 of copending Application No. 18/682,782 in view of Valamehr et al, Blazar et al, and DiPersio et al
Applicant has amended independent claim 1 to require the expression of CD47 to be sufficiently increased such that the release of interferon gamma by NK cells is reduced, as well as the hypoimmunogenic T cell to be CD8+CD45RA+CCR7-. As Applicant has narrowed the scope of a previously recited limitation and presented a new limitation that has previously not been considered, Applicant’s amendments obviate the rejection of record.
Therefore, the rejection is withdrawn.
However, Applicant’s arguments are addressed in so far as they are applicable to the new rejection of record:
Applicant has requested in Pages 14-15 of the Remarks filed 24 November 2025 that the rejection be held in abeyance. In response, the Examiner respectfully reminds Applicant that 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. Applicant did not traverse the NSDP rejection.
New Grounds of Rejection
Claim Interpretation
In light of the discussion above, the broadest reasonable interpretation of amended claim 1 is interpreted as:
A hypoimmunogenic T cell comprising a nucleic acid encoding a chimeric antigen receptor (CAR), wherein:
(i) endogenous beta-2 microglobulin (B2M) gene activity and endogenous class II transactivator (CIITA) gene activity are eliminated;
(ii) CD47 expression is increased when compared to a wild-type T cell; and
(iii) the hypoimmunogenic T cell is CD8+ CD45RA+ CCR7-.
Claim Objections
Claims 1 and 3 are objected to because of the following informalities:
Regarding claim 1: The instant claim is objected to for reciting “wild-type” in Line 7 and “wild type” in Line 11. Applicant must amend the claim such that the recitation of the term is consistent throughout the claim language.
Appropriate correction is required.
Regarding claim 3: The instant claim is objected to for reciting “CDI171” instead of “CD171” in Line 2.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 60 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.
Regarding claim 60: The instant claim recites the limitation, “wherein the hypoimmunogenic T cell is a CD3+ T cell, a CD8+ T cell, a CD8+ low T cell, a CD8+ high T cell, a CD4+ T cell, a CD4+/CD8+ high T cell, or a CD4+/CD8+ low T cell”. As parent claim 1 already lists the hypoimmunogenic T cell as being CD8+CD45RA+CCR7-, instant claim 60 does not further limit the claim from which it depends.
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
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102
and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 4, 8, 10-14, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Valamehr et al (WO 2017/079673 A1, of record) as evidenced by Sallusto et al (Nature, 1999).
Valamehr et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Sallusto et al is considered prior art under 35 USC 102(a)(1).
Regarding claims 1 and 60: Valamehr et al disclose induced pluripotent stem cell (iPSC)-derived T cells comprising a chimeric antigen receptor (CAR), wherein the endogenous B2M and CIITA genes have been deleted and wherein CD47 expression has been increased (Paragraphs [0006], [00022]-[00023], [00028], [000149], [000216]). With that, Valamehr et al disclose that the CD47 expression is increased via the introduction of an exogenous CD47 gene under control of a constitutive promoter, and that the expression is increased relative to the wildtype expression – meaning low expression or non-expression – of CD47 within the cell (Paragraphs [00019], [00022], [00025], [00030]).
Valamehr et al further disclose that the iPSC-derived T cells having deleted endogenous B2M and CIITA genes and increased CD47 expression have an improved persistency, increased resistance to immune cells, increased resistance to NK cells, and/or increased immune-resistance in comparison to cells without the same genomic engineering (Paragraphs [00020]-[00022], [000146], [000215]).
Valamehr et al further disclose that the iPSC-derived T cells are mammalian – or human – CD3+ naïve or memory T cells, including central memory T cells (Tcm cells) and effector memory T cells (Tem cells and TEMRA cells) (Paragraphs [000106], [000113]). It is of note that TEMRA cells are inherently CD8+CD45RA+CCR7-, as evidenced by Sallusto et al. See Page 710 of Sallusto et al.
Valamehr et al do not exemplify or reduce to practice that a B2M/CIITA null CAR-T cell comprising exogenous CD47 has a sufficient increase in CD47 expression to reduce the release of interferon gamma by NK cells, as required by instant claim 1.
Therefore, it would have been prima facie obvious to reduce to practice a recombinant T cell that comprises a CAR as well as an eliminated B2M and CIITA, wherein the T cell further expresses exogenous CD47. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to create the T cells taught by Valamehr et al, and would have had a reasonable expectation of success given that Valamehr et al disclose how to generate each modification to the T cell. See MPEP § 2143(I)(G).
Consequently, Valamehr et al as evidenced by Sallusto et al render obvious induced pluripotent stem cell (iPSC)-derived T cells comprising a chimeric antigen receptor (CAR), wherein the endogenous B2M and CIITA genes have been deleted, and CD47 expression is increased compared to wildtype expression. With that, Valamehr et al further disclose that the iPSC-derived T cells are TEMRA cells, which are inherently CD8+CD45RA+CCR7- (claim 60). Given the Claim Interpretation section above, this therefore renders obvious the hypoimmunogenic T cell of instant claim 1. See MPEP § 2111.04.
Regarding claims 2 and 4: Following the discussion of claim 1, Valamehr et al further disclose that CARs are fusion proteins comprising a single-chain variable fragment (scFv) (claim 4) derived from monoclonal antibodies to provide antigen recognition and a combination of intracellular signaling domains (claim 2) to provide activation signals to the T cell (Paragraph [000317]). This therefore reads on the hypoimmunogenic T cell of the instant claims.
Regarding claims 8 and 10: Following the discussion of claim 1, Valamehr et al further disclose that the iPSC-derived T cells are human T cells, and that the CD47 expression is increased via the introduction of an exogenous CD47 gene under control of a constitutive promoter (claim 10) (Paragraphs [000106], [00019], [00022], [00025], [00030], [000113]). Therefore, the endogenous B2M and CIITA that are deleted from the human iPSCs will inherently be human genes (Paragraphs [000120]-[000122], [000260]).
Valamehr et al do not disclose that the exogenous CD47 gene is a human gene, as required by instant claim 8.
However, it would have been prima facie obvious to have inserted human CD47 genes into the human T cells, as the ordinary artisan would have been motivated to match the host cell species, and would have had a reasonable expectation of success due to the protocols outlined in Valamehr et al (Paragraph [000170]). See MPEP § 2143(I)(G). This therefore renders obvious the hypoimmunogenic T cell of instant claim 8.
Regarding claims 11-12: Following the discussion of claim 1, Valamehr et al further disclose that the B2M (claim 11) and CIITA (claim 12) genes are deleted via the disruption of the endogenous gene expression using targeted genomic editing (Paragraph [000149]). This therefore reads on the hypoimmunogenic T cell of the instant claims.
Regarding claims 13-14: Following the discussion of claim 1, Valamehr et al further disclose that the iPSC-derived CAR T cells comprise a suicide gene encoding safety switch proteins (claim 13), wherein the suicide gene system includes herpes complex virus thymidine kinase and ganciclovir (claim 14) (Paragraphs [00021]-[00022], [00027] [000166]). This therefore reads on the hypoimmunogenic T cell of the instant claims.
Claims 1-6, 8, 10-15, and 60-61 are rejected under 35 U.S.C. 103 as being unpatentable over Valamehr et al (WO 2017/079673 A1, of record) as evidenced by Sallusto et al (Nature, 1999), and in view of DiPersio et al (US 2020/0109364 A1, of record).
The discussion of Valamehr et al as evidenced by Sallusto et al regarding claims 1-2 and 13-14 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Valamehr et al as evidenced by Sallusto et al render obvious claims 1-2, 4, 8, 10-14, and 60. DiPersio et al is considered prior art under 35 U.S.C. 102(a)(2).
Regarding claims 3, 5-6, 15, and 61: As aforementioned in the discussion of claims 2 and 14 above, Valamehr et al disclose induced pluripotent stem cell (iPSC)-derived T cells comprising a chimeric antigen receptor (CAR) and herpes complex virus thymidine kinase and ganciclovir suicide gene system, wherein the endogenous B2M and CIITA genes have been deleted and wherein CD47 expression has been increased (Paragraphs [0006], [00022]-[00023], [000149]). With that, Valamehr et al disclose that the CAR comprises a single-chain variable fragment (scFv) derived from monoclonal antibodies to provide antigen recognition and intracellular signaling domains (Paragraph [000317]).
Valamehr et al further disclose CD19-specific CAR-T cells having a truncated LNGFR cell surface marker for use in different therapeutic methods relating to cancer (Paragraphs [000317]-[000318]).
Valamehr et al fail to teach the composition of the domains and regions comprised within the CAR, as required by instant claims 3 and 5-6.
DiPersio et al, however, disclose engineered chimeric antigen receptor (CAR)-bearing T cells for use in methods of immunotherapy (Abstract).
As such, DiPersio et al disclose CARs comprising an extracellular domain that binds to CD19, a CD8α transmembrane domain with a IgG1 hinge region, as well as a CD3ζ intracellular signaling domain (Paragraphs [0248], [0253]- [0259]).
DiPersio et al further disclose that the CAR-bearing T cells may further comprise a suicide gene system including herpes simplex virus thymidine kinase (HSVtk) and ganciclovir (GCV) (Paragraph [0260]). With that, DiPersio et al disclose a CAR construct comprising the HSVtk/GCV suicide gene system within SEQ ID NO: 4, which has 99.3% sequence identity to instant SEQ ID NO: 4. See sequence alignment below.
Therefore, it would have been prima facie obvious to transduce the iPSC-derived T cells of Valamehr et al as evidenced by Sallusto et al with the chimeric antigen receptor and suicide gene system detailed in DiPersio et al. One of ordinary skill before the effective filing date of the invention would have been motivated to utilize a CAR construct with corresponding suicide gene system that is effective in treating multiple myeloma via adoptive cell therapy, and would have had a reasonable expectation of success since both Valamehr et al and DiPersio et al teach CD19-specific CAR T cells for use in immunotherapeutic methods – especially concerning the treatment of multiple myeloma (Valamehr et al, Paragraph [000219]; DiPersio et al, Paragraph [0253]) – and would thereby require minimal adaption when generating the iPSC-derived CAR T cells. See MPEP § 2143(I)(G).
Consequently, Valamehr et al as evidenced by Sallusto et al and as modified by DiPersio et al render obvious an iPSC-derived T cell comprising a CAR and HSVtk/GCV suicide gene system comprised within SEQ ID NO: 4 (claim 15), wherein the CAR comprises an extracellular domain that binds to CD19 (claim 3), a CD8α transmembrane domain (claim 5) with a IgG1 hinge region (claim 61), as well as a CD3ζ intracellular signaling domain (claim 6). This therefore renders obvious the hypoimmunogenic T cell of the instant claims.
Query Match 99.3%; Matches 372; Conservative 2; Mismatches 2; Gaps 0
Qy 1 MASYPCHQHASAFDQAARSRGHSNRRTALRPRRQQEATEVRLEQKMPTLLRVYIDGPHGM 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 858 MASYPCHQHASAFDQAARSRGHSNRRTALRPRRQQEATEVRLEQKMPTLLRVYIDGPHGM 917
Qy 61 GKTTTTQLLVALGSRDDIVYVPEPMTYWQVLGASETIANIYTTQHRLDQGEISAGDAAVV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 918 GKTTTTQLLVALGSRDDIVYVPEPMTYWQVLGASETIANIYTTQHRLDQGEISAGDAAVV 977
Qy 121 MTSAQITMGMPYAVTDAVLAPHVGGEAGSSHAPPPALTLIFDRHPIAALLCYPAARYLMG 180
|||||||||||||||||||||||||||||||||||||||: |||||| :|||||||||||
Db 978 MTSAQITMGMPYAVTDAVLAPHVGGEAGSSHAPPPALTLLLDRHPIAVMLCYPAARYLMG 1037
Qy 181 SMTPQAVLAFVALIPPTLPGTNIVLGALPEDRHIDRLAKRQRPGERLDLAMLAAIRRVYG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1038 SMTPQAVLAFVALIPPTLPGTNIVLGALPEDRHIDRLAKRQRPGERLDLAMLAAIRRVYG 1097
Qy 241 LLANTVRYLQGGGSWWEDWGQLSGTAVPPQGAEPQSNAGPRPHIGDTLFTLFRAPELLAP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1098 LLANTVRYLQGGGSWWEDWGQLSGTAVPPQGAEPQSNAGPRPHIGDTLFTLFRAPELLAP 1157
Qy 301 NGDLYNVFAWALDVLAKRLRPMHVFILDYDQSPAGCRDALLQLTSGMVQTHVTTPGSIPT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1158 NGDLYNVFAWALDVLAKRLRPMHVFILDYDQSPAGCRDALLQLTSGMVQTHVTTPGSIPT 1217
Qy 361 ICDLARTFAREMGEAN 376 (Instant SEQ ID NO:4)
||||||||||||||||
Db 1218 ICDLARTFAREMGEAN 1233 (Ref SEQ ID NO: 4)
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 1-6, 8, 10-15, and 60-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4 and 31 of copending Application No. 17/632,026 in view of Valamehr et al (WO 2017/079673 A1, of record) as evidenced by Sallusto et al (Nature, 1999), and DiPersio et al (US 2020/0109364 A1, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims. More specifically, the copending claims are not identical because no single copending claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate copending claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the copending application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
It is of note that the limitation comprised within instant claim 1 wherein the increased expression of CD47 is sufficient to reduce the release of interferon gamma by NK cells is a contingent limitation. See Claim Interpretation section above. Therefore, the cited claims need only render obvious the structure, and not the effect, of the instant claims.
Copending claim 1 is directed to an isolated cell comprising a modification to reduce cell surface expression of MHC class II human leukocyte antigens and a modification to increase expression of DUX4 in the cell, wherein the increased expression of DUX4 reduces cell surface expression of MHC class I human leukocyte antigens.
Copending claim 3 further limits the isolated cell of copending claim 1, wherein the cell further comprises a genetic modification that inactivates the CIITA gene, and a genetic modification that inactivates the B2M gene.
Copending claim 4 further limits the isolated cell of copending claim 1, wherein the cell further comprises a modification to increase expression of CD47.
Copending claim 31 further limits the isolated cell of copending claim 1, wherein the cell is a chimeric antigen receptor T cell.
The combination of copending claims 1-4 and 31 fail to teach that that the isolated chimeric antigen receptor T cell is CD8+CD45RA+CCR7-.
However, the use of CD8+CD45RA+CCR7- cells – or TEMRA cells – was known in the art by Valamehr et al as evidenced by Sallusto et al.
Valamehr et al disclose induced pluripotent stem cell (iPSC)-derived T cells comprising a chimeric antigen receptor (CAR), wherein the endogenous B2M and CIITA genes have been deleted and wherein CD47 expression has been increased (Paragraphs [0006], [00022]-[00023], [00028], [000149], [000216]). Valamehr et al further disclose that the iPSC-derived T cells are mammalian – or human – CD3+ naïve or memory T cells, including central memory T cells (Tcm cells) and effector memory T cells (Tem cells and TEMRA cells) (Paragraphs [000106], [000113]).
Therefore, it would have been prima facie obvious to have modified the claims of the copending application such that the B2M/CIITA null CAR-T cells are CD8+CD45RA+CCR7-. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to produce the TEMRA cells, and would have had a reasonable expectation of success given that Valamehr et al reasonably suggest an iPSC-derived T cell comprising the elimination of the endogenous B2M and CIITA genes and expression of a CAR and increased CD47, wherein the cells are TEMRA cells (Paragraphs [00020]-[00023], [00030], [00033], [000146], [000216]).
Consequently, copending claims 1-4 and 31 as modified by Valamehr et al as evidenced by Sallusto et al render obvious instant claim 1.
With that, instant claims 2-6, 8, 10-15, and 60-61 are known from the copending claims or prior art and can be further incorporated into the isolated cell rendered obvious by copending claims 1-4 and 31 as modified by Valamehr et al as evidenced by Sallusto et al:
Copending claim 3 teaches the limitations recited in instant claims 11-12.
Valamehr et al further teach the limitations recited in instant claims 2, 4, 8, 10, 13-14, and 60.
DiPersio et al teach the limitations recited in instant claims 3, 5-6, 15, and 61.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 8, 10-15, and 60-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, and 27 of copending Application No. 17/637,789 in view of Valamehr et al (WO 2017/079673 A1, of record) as evidenced by Sallusto et al (Nature, 1999) and DiPersio et al (US 2020/0109364 A1, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims. More specifically, the copending claims are not identical because no single copending claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate copending claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the copending application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
It is of note that the limitation comprised within instant claim 1 wherein the increased expression of CD47 is sufficient to reduce the release of interferon gamma by NK cells is a contingent limitation. See Claim Interpretation section above. Therefore, the cited claims need only render obvious the structure, and not the effect, of the instant claims.
Copending claim 1 is directed to an isolated cell comprising reduced cell surface expression of MHC class I and/or MHC class II human leukocyte antigens and a modification to increase expression of CD24 in the cell, wherein the cell has a reduced susceptibility to macrophage phagocytosis compared to an unmodified cell.
Copending claims 2-3 and 5 further limit the isolated cell of copending claim 1, wherein the cell further comprises a genetic modification targeting a CIITA gene by a rare-cutting endonuclease that selectively inactivates the CIITA gene, a genetic modification targeting a B2M gene by a rare-cutting endonuclease that selectively inactivates the B2M gene, and a modification to increase expression of CD47.
Copending claim 27 further limits the isolated cell of copending claim 1, wherein the cell is a chimeric antigen receptor T cell.
The combination of copending claims 1-3, 5, and 27 fail to teach that the increased expression of CD47 is sufficient to reduce the release of interferon gamma by NK cells, nor that the isolated chimeric antigen receptor T cell is CD8+CD45RA+CCR7-.
However, the use of CD8+CD45RA+CCR7- cells – or TEMRA cells – was known in the art by Valamehr et al as evidenced by Sallusto et al.
Valamehr et al disclose induced pluripotent stem cell (iPSC)-derived T cells comprising a chimeric antigen receptor (CAR), wherein the endogenous B2M and CIITA genes have been deleted and wherein CD47 expression has been increased (Paragraphs [0006], [00022]-[00023], [00028], [000149], [000216]). Valamehr et al further disclose that the iPSC-derived T cells are mammalian – or human – CD3+ naïve or memory T cells, including central memory T cells (Tcm cells) and effector memory T cells (Tem cells and TEMRA cells) (Paragraphs [000106], [000113]).
Therefore, it would have been prima facie obvious to have modified the claims of the copending application such that the B2M/CIITA null CAR-T cells are CD8+CD45RA+CCR7-. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to produce the TEMRA cells, and would have had a reasonable expectation of success given that Valamehr et al reasonably suggest an iPSC-derived T cell comprising the elimination of the endogenous B2M and CIITA genes and expression of a CAR and increased CD47, wherein the cells are TEMRA cells (Paragraphs [00020]-[00023], [00030], [00033], [000146], [000216]).
Consequently, copending claims 1-3, 5, and 27 as modified by Valamehr et al as evidenced by Sallusto et al render obvious instant claim 1.
With that, instant claims 2-6, 8, 10-15, and 60-61 are known from the copending claims or prior art and can be further incorporated into the isolated cell rendered obvious by copending claims 1-3, 5, and 27 as modified by Valamehr et al as evidenced by Sallusto et al:
Copending claims 3 and 5 teach the limitations recited in instant claims 11-12.
Valamehr et al further teach the limitations recited in instant claims 2, 4, 8, 10, 13-14, and 60.
DiPersio et al teach the limitations recited in instant claims 3, 5-6, 15, and 61.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 8, 10-15, and 60-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 410, 413-415, 421-422 of copending Application No. 18/682,782 in view of Valamehr et al (WO 2017/079673 A1, of record) as evidenced by Sallusto et al (Nature, 1999), and DiPersio et al (US 2020/0109364 A1, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims. More specifically, the copending claims are not identical because no single copending claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate copending claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the copending application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
It is of note that the limitation comprised within instant claim 1 wherein the increased expression of CD47 is sufficient to reduce the release of interferon gamma by NK cells is a contingent limitation. See Claim Interpretation section above. Therefore, the cited claims need only render obvious the structure, and not the effect, of the instant claims.
Copending claim 410 is directed to an engineered cell comprising modifications that (i) increase expression of one or more tolerogenic factors, (ii) increase expression of CD46, (iii) increase expression of CD59, and (iv) reduce expression of one or more MHC class I molecules and/or one or more MHC class II molecules, wherein the increased expression of (i), (ii), and (iii) and the reduced expression of (iv) is relative to a cell of the same cell type that does not comprise the modifications.
Copending claim 413 further limits the engineered cell of copending claim 410, wherein the tolerogenic factor having an increased expression is CD47.
Copending claims 414-415 further limit the engineered cell of copending claim 410, wherein the cell further comprises a modification that inactivates both alleles of the B2M gene and both alleles of the CIITA gene.
Copending claims 421-422 further limit the engineered cell of copending claim 410, wherein the cell is a chimeric antigen receptor T cell.
The combination of copending claims 410, 413-415, and 421-422 fail to teach that the isolated chimeric antigen receptor T cell is CD8+CD45RA+CCR7-.
However, the use of CD8+CD45RA+CCR7- cells – or TEMRA cells – was known in the art by Valamehr et al as evidenced by Sallusto et al.
Valamehr et al disclose induced pluripotent stem cell (iPSC)-derived T cells comprising a chimeric antigen receptor (CAR), wherein the endogenous B2M and CIITA genes have been deleted and wherein CD47 expression has been increased (Paragraphs [0006], [00022]-[00023], [00028], [000149], [000216]). Valamehr et al further disclose that the iPSC-derived T cells are mammalian – or human – CD3+ naïve or memory T cells, including central memory T cells (Tcm cells) and effector memory T cells (Tem cells and TEMRA cells) (Paragraphs [000106], [000113]).
Therefore, it would have been prima facie obvious to have modified the claims of the copending application such that the B2M/CIITA null CAR-T cells are CD8+CD45RA+CCR7-. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to produce the TEMRA cells, and would have had a reasonable expectation of success given that Valamehr et al reasonably suggest an iPSC-derived T cell comprising the elimination of the endogenous B2M and CIITA genes and expression of a CAR and increased CD47, wherein the cells are TEMRA cells (Paragraphs [00020]-[00023], [00030], [00033], [000146], [000216]).
Consequently, copending claims 410, 413-415, and 421-422 as modified by Valamehr et al as evidenced by Sallusto et al render obvious instant claim 1.
With that, instant claims 2-6, 8, 10-15, and 60-61 are known from the copending claims or prior art and can be further incorporated into the isolated cell rendered obvious by copending claims 410,
413-415, and 421-422 as modified by Valamehr et al as evidenced by Sallusto et al:
Valamehr et al further teach the limitations recited in instant claims 2, 4, 8, 10-14, and 60.
DiPersio et al teach the limitations recited in instant claims 3, 5-6, 15, and 61.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 8, 10-15, and 60-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 312, 314-315, 317, 325-326, and 328-329 of copending Application No. 18/021,036 in view of Valamehr et al (WO 2017/079673 A1, of record) as evidenced by Sallusto et al (Nature, 1999), and DiPersio et al (US 2020/0109364 A1, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims. More specifically, the copending claims are not identical because no single copending claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate copending claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the copending application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
It is of note that the limitation comprised within instant claim 1 wherein the increased expression of CD47 is sufficient to reduce the release of interferon gamma by NK cells is a contingent limitation. See Claim Interpretation section above. Therefore, the cited claims need only render obvious the structure, and not the effect, of the instant claims.
It is also of note that, although the copending application is directed to a method of using hypoimmunogenic cells, instant claim 1 is an obvious variant of the copending claims in view of the art:
Copending claim 312 is directed to a method of treating a disease, disorder, or condition in a patient comprising administering a population of hypoimmunogenic cells, wherein the population of hypoimmunogenic cells have been modified: (i) to express one or more tolerogenic factors, and (ii) to include one or more genomic modifications that reduce cell surface expression of major histocompatibility complex (MHC) class I molecules, MHC class II molecules, or both, wherein the reduced cell surface expression is relative to a reference cell of the same cell type that does not comprise the one or more genomic modifications; and wherein the patient is a sensitized patient.
Copending claim 314 further limits the method of copending claim 312, wherein the one or more genomic modifications that reduce cell surface expression of MHC class I molecules and MHC class II molecules comprise one or modifications that reduce expression of B2M and CIITA.
Copending claim 315 further limits the method of copending claim 312, wherein the tolerogenic factor having an increased expression is CD47.
Copending claim 317 further limits the method of copending claim 312, wherein the hypoimmunogenic cell is a chimeric antigen receptor T cell.
The combination of copending claims 312, 314-315, and 317 fail to teach that the isolated chimeric antigen receptor T cell is CD8+CD45RA+CCR7-.
However, the use of CD8+CD45RA+CCR7- cells – or TEMRA cells – was known in the art by Valamehr et al as evidenced by Sallusto et al.
Valamehr et al disclose induced pluripotent stem cell (iPSC)-derived T cells comprising a chimeric antigen receptor (CAR), wherein the endogenous B2M and CIITA genes have been deleted and wherein CD47 expression has been increased (Paragraphs [0006], [00022]-[00023], [00028], [000149], [000216]). Valamehr et al further disclose that the iPSC-derived T cells are mammalian – or human – CD3+ naïve or memory T cells, including central memory T cells (Tcm cells) and effector memory T cells (Tem cells and TEMRA cells) (Paragraphs [000106], [000113]).
Therefore, it would have been prima facie obvious to have modified the claims of the copending application such that the B2M/CIITA null CAR-T cells are CD8+CD45RA+CCR7-. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to produce the TEMRA cells, and would have had a reasonable expectation of success given that Valamehr et al reasonably suggest an iPSC-derived T cell comprising the elimination of the endogenous B2M and CIITA genes and expression of a CAR and increased CD47, wherein the cells are TEMRA cells (Paragraphs [00020]-[00023], [00030], [00033], [000146], [000216]).
Consequently, copending claims 312, 314-315, and 317 as modified by Valamehr et al as evidenced by Sallusto et al render obvious instant claim 1.
With that, instant claims 2-6, 8, 10-15, and 60-61 are known from the copending claims or prior art and can be further incorporated into the isolated cell rendered obvious by copending claims 312, 314-315, and 317 as modified by Valamehr et al as evidenced by Sallusto et al:
Copending claims 325-326 and 328-329 teach the limitations recited in instant claims 2-4.
Valamehr et al further teach the limitations recited in instant claims 8, 10-14, and 60.
DiPersio et al teach the limitations recited in instant claims 5-6, 15, and 61.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 8, 10-15, and 60-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 189, 198-199, and 205-209 of copending Application No. 18/561,682 in view of Valamehr et al (WO 2017/079673 A1, of record) as evidenced by Sallusto et al (Nature, 1999), and DiPersio et al (US 2020/0109364 A1, of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims. More specifically, the copending claims are not identical because no single copending claim discloses all of the limitations of any of the instant claims; however, each of the limitations of the instant claims are disclosed by separate copending claims, or rendered obvious by the accompanying prior art. The fact that each of the elements were claimed in the copending application, just not in a single claim, still renders obvious the instant invention because each of the features, though separately claimed, can be physically combined into a single embodiment.
It is of note that the limitation comprised within instant claim 1 wherein the increased expression of CD47 is sufficient to reduce the release of interferon gamma by NK cells is a contingent limitation. See Claim Interpretation section above. Therefore, the cited claims need only render obvious the structure, and not the effect, of the instant claims.
It is also of note that, although the copending application is directed to a method of using hypoimmunogenic cells, instant claim 1 is an obvious variant of the copending claims in view of the art:
Copending claim 189 is directed to a method of treating a disease, disorder, or condition in a patient comprising administering a therapeutically effective population of hypoimmunogenic T cells, wherein the population of hypoimmunogenic T cells have been modified: (i) to express one or more tolerogenic factors, (ii) to include one or more genomic modifications that reduce cell surface expression of major histocompatibility complex (MHC) class I molecules, MHC class II molecules, or both, wherein the reduced cell surface expression is relative to a reference cell of the same cell type that does not comprise the one or more genomic modifications, (iii) to include one or more genetic modifications to reduce expression of RhD antigen, wherein the reduced expression is relative to a reference cell of the same cell type that does not comprise the one or more genetic modifications; and wherein the hypoimmunogenic T cells are propagated from a primary T cell or a progeny thereof, or are derived from an iPSC or a progeny thereof, and wherein the patient is RhD sensitized.
Copending claim 198 further limits the method of copending claim 189, wherein the one or more genomic modifications that reduce cell surface expression of MHC class I molecules and MHC class II molecules comprise one or modifications that reduce expression of B2M and CIITA.
Copending claim 199 further limits the method of copending claim 189, wherein the tolerogenic factor having an increased expression is CD47.
Copending claim 205 further limits the method of copending claim 189, wherein the hypoimmunogenic cell is a chimeric antigen receptor T cell.
The combination of copending claims 189, 198-199, and 205 fail to teach that the increased expression of CD47 is sufficient to reduce the release of interferon gamma by NK cells and/or phagocytosis by macrophages, not that the isolated chimeric antigen receptor T cell is CD8+CD45RA+CCR7-.
However, the use of CD8+CD45RA+CCR7- cells – or TEMRA cells – was known in the art by Valamehr et al as evidenced by Sallusto et al.
Valamehr et al disclose induced pluripotent stem cell (iPSC)-derived T cells comprising a chimeric antigen receptor (CAR), wherein the endogenous B2M and CIITA genes have been deleted and wherein CD47 expression has been increased (Paragraphs [0006], [00022]-[00023], [00028], [000149], [000216]). Valamehr et al further disclose that the iPSC-derived T cells are mammalian – or human – CD3+ naïve or memory T cells, including central memory T cells (Tcm cells) and effector memory T cells (Tem cells and TEMRA cells) (Paragraphs [000106], [000113]).
Therefore, it would have been prima facie obvious to have modified the claims of the copending application such that the B2M/CIITA null CAR-T cells are CD8+CD45RA+CCR7-. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to produce the TEMRA cells, and would have had a reasonable expectation of success given that Valamehr et al reasonably suggest an iPSC-derived T cell comprising the elimination of the endogenous B2M and CIITA genes and expression of a CAR and increased CD47, wherein the cells are TEMRA cells (Paragraphs [00020]-[00023], [00030], [00033], [000146], [000216]).
Consequently, copending claims 189, 198-199, and 205 as modified by Valamehr et al as evidenced by Sallusto et al render obvious instant claim 1.
With that, instant claims 2-6, 8, 10-15, and 60-61 are known from the copending claims or prior art and can be further incorporated into the isolated cell rendered obvious by copending claims 189, 198-199, and 205 as modified by Valamehr et al as evidenced by Sallusto et al:
Copending claims 206-209 teach the limitations recited in instant claims 2-4.
Valamehr et al further teach the limitations recited in instant claims 8, 10-14, and 60.
DiPersio et al teach the limitations recited in instant claims 5-6, 15, and 61.
This is a provisional nonstatutory double patenting rejection.
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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633