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 .
Amendments
In the reply filed 10/21/2025, Applicant has amended claims 1-2, 8-9, 11, 13 and 27, and has canceled claims 3-5, 14-25, 28 and 29.
Claim Status
Claims 1-2, 6-13 and 26-27 are pending.
Claims 26-27 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/05/2025.
Claims 1-2 and 6-13 are considered on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/21/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. The corresponding signed and initialed PTO form 1449 has been mailed with this action.
Withdrawn Specification Objections
The prior objection to the disclosure because of an embedded hyperlink is withdrawn in light of Applicant’s amendment to the specification.
Withdrawn Claim Objections
The prior objection to claims 8 and 13 because of typographic errors is withdrawn in light of Applicant’s amendment to the claims.
Withdrawn Claim Rejections - 35 USC § 112
The prior rejection of claim 11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in light of Applicant’s amendment to the claim.
New Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 13 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 (ii) recites the limitation “a second heterologous nucleic acid sequence” encoding SERPINB9. Since amended base claim 1 recites “(ii) a heterologous nucleic acid sequence” encoding SERPINB9, it is not clear whether this “second” sequence in claim 13 (ii) refers to the same sequence in claim 1 (ii) or not. If they are the same, it is recommended to change the limitation in claim 13 (ii) to “the heterologous nucleic acid sequence” encoding SERPINB9. For examination purposes the claim will be interpreted as reciting the same heterologous nucleic acid sequence.
Withdrawn Claim Rejections - 35 USC § 112(a)
(Written Description)
The prior rejection of claims 1-2 and 6-13 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s arguments.
Response to Traversal:
Applicant’s arguments filed on 10/21/2025 are acknowledged.
Applicant argues that the presently claimed sequences for CLEC2D, SERPINB9 and TRAIL are transmembrane proteins and numerous conservative substitutions could be made outside of ligand-interacting or intracellular signaling domains that would exceed the claimed percent identity threshold, as the specification discloses 13 amino acid sequences of CLEC2D and demonstrates one (SEQ ID NO: 2) with immune evasion. The skilled person would reasonably expect that variants within 95% identity would preserve the immune evasion effects demonstrated by Applicant’s disclosure (Remarks, p. 15-16).
Applicant’s arguments have been fully considered and they are persuasive. Therefore, the prior rejection under 35 U.S.C. 112(a) has been withdrawn.
Maintained Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 and 8-9 stand rejected under 35 U.S.C. 103 as being unpatentable over Nagy et al., (WO 2018/227286 A1. Prior art of record) in view of Braud et al., (US 2009/0074756A1. Prior art of record) and NCBI alignment (NCBI TNFSF10 alignment with SEQ ID NO: 4. P. 1-5. Prior art of record).
It is noted that the prior rejection mailed on 08/26/2025 is maintained. The instant action is edited solely to address the amendment.
With respect to claims 1 and 2, Nagy teaches enhancing allograft tolerance by genetically modifying a cell for providing a local immunosuppression at a transplant site when transplanted in an allogeneic host (e.g., abstract, p. 7, para 2). Nagy teaches the genetically modified cell may be a human stem cell (p. 42, para 2) or an induced pluripotent stem (iPS) cells (p. 42, last para) that are of use in cell-based therapies wherein it is desirable to evade allorejection at a localized transplant site, thus teaches the preamble of claim 1.
Regarding limitation (ii) directed to SERPINB9, Nagy teaches the genetically modified stem cell comprises a set of transgenes comprising Serpin B9 to protect against leukocyte-mediated apoptosis (e.g., p. 7, para 3 and p. 28, last para-p. 29, 1st para), related to claim 1 (ii), and Tnfsf10 to induce apoptosis in graft attacking leukocytes (p. 28, para 2. Note that Tnfsf10 is also known as TRAIL), related to claim 2. Regarding the amino acid sequence of SERPINB9, Nagy teaches a human SERPIN B9 amino acid sequence in page 38 (reference SEQ ID NO: 8) that is 100% identical to the instant SEQ ID NO: 6 (see below).
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However, Nagy is silent on a heterologous CLEC2D comprising an amino acid sequence at least 95% identical to SEQ ID NO: 2 in claim 1 (i).
Braud teaches modulating the activity of cells expressing LLT1 (also known as CLEC2D) for the treatment of organ and bone marrow transplantation rejection (e.g., abstract, [0045] and reference claim 54) and teaches expression of LLT1 in graft cells, such as porcine endothelial cells in case of porcine xenotransplantation, may directly protect sensitive graft cells from human NK cell-mediated xenogeneic cytotoxicity (e.g., [0063]). Braud teaches in working examples that various NK cell targets, such as 293T, C1R, K562, Hela, 721.221, and P815 cell lines, are transfected to express LLT1 ([0189], see Fig 11), which induces down-regulation of CD161 (see Example 3 in page 8) and inhibits polyclonal IL-2 activated NK cell-mediated cytotoxicity (see Examples 4-5 in p. 9 and Figs 7 and 12). In regard to the amino acid sequence of CLEC2D, Braud teaches the LLT1 (CLEC2D) amino acid sequence in [0180] and reference SEQ ID NO: 2, which is 100% identical to instant SEQ ID NO: 2 (see below).
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Thus, Braud teaches a genetically modified cell (such as a 293T cell or a graft cell) comprising a heterologous nucleic acid sequence encoding CLEC2D (i.e., transfected with LLT1 cDNA sequence, see [0181] and [0189]), wherein CLEC2D comprises an amino acid sequence at least 95% identical to the sequence of SEQ ID NO: 2, and the genetically modified cell has reduced NK cell-mediated cytotoxicity, related to claim 1 (i).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the genetically modified stem cell to evade allorejection at a localized transplant site when transplanted in an allogeneic host disclosed by Nagy, by combining a heterologous CLEC2D comprising an amino acid sequence at least 95% identical to SEQ ID NO: 2 as taught by Braud with a reasonable expectation of success. Since Nagy aims to enhance allograft tolerance by genetically modifying stem cells with a set of transgenes for providing a local immunosuppression at a transplant site when transplanted in an allogeneic host (p. 7, para 2), and since Braud teaches expression of LLT1 in graft cells directly protect sensitive graft cells from NK cell-mediated cytotoxicity (e.g., [0063]) and demonstrates transfecting cells with LLT1 (CLEC2D) inhibits polyclonal IL-2 activated NK cell-mediated cytotoxicity (see Examples 4-5 in p. 9 and Figs 7 and 12), one of ordinary skill in the art would have had a reason to combine a heterologous CLEC2D gene in the genetically modified stem cell of Nagy in order to protect sensitive graft cells from NK cell-mediated cytotoxicity to enhance allograft tolerance.
With respect to claim 2, as stated supra, Nagy teaches the transgenes further comprise Tnfsf10 to induce apoptosis in graft attacking leukocytes (p. 28, para 2. Note that Tnfsf10 is also known as TRAIL). NCBI alignment demonstrates the human TNFSF10 amino acid sequence (NCBI Reference Sequence NP_003801.1, see NCBI alignment, p. 3-5) is 100% identical to the instant SEQ ID NO: 4 (see NCBI alignment, p. 1-2).
Accordingly, one of ordinary skill in the art would have chosen the amino acid sequence of human TNFSF10 (TRAIL) as taught by NCBI alignment in the stem cell of Nagy for administration into a human patient receiving a transplant (e.g., p. 79, para “Pharmaceutical compositions”).
With respect to claim 8 directed to the stem cell being at least 20% less susceptible to natural killer cell mediated cytotoxicity as compared to a wild-type stem cell, Braud teaches in working examples that various NK cell targets, such as 293T, is transfected to express LLT1 ([0189], see Fig 11), which inhibits polyclonal IL-2 activated NK cell-mediated cytotoxicity and a 28.3% lysis decrease is observed for LLT1 expressing 293T cells with respect to control cells ([0195], Example 4, and Fig 7). Accordingly, one of ordinary skill in the art would have appreciated that the genetically modified stem cell comprising a heterologous CLEC2D (LLT1) of Nagy in view of Braud would have had at least 20% less susceptible to natural killer cell mediated cytotoxicity as compared to a wild-type stem cell.
With respect to claim 9 directed to the stem cell comprising a human pluripotent stem cell, as stated supra, Nagy teaches the genetically modified stem cell may be a human stem cell (p. 42, para 2) and an induced pluripotent stem (iPS) cells (p. 42, last para).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 10/21/2025 are acknowledged.
Applicant firstly argues that (1) the cited art does not teach or suggest expressing CLEC2D in stem cells because prior art Nagy does not teach CLEC2D and Braud does not teach stem cells, and thus there is no teaching or motivation to combine (Remarks, p. 18-19 and p. 22).
Applicant’s arguments have been fully considered but they are not persuasive.
As a first matter, Applicant is reminded 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, as Applicant has pointed out, Nagy has done extensive experimentation with various transgene combinations to evaluate stem cell immune invasion, including SERPIN B9 (also known as SPI6) and TNFSF10 (also known as TRAIL) (see e.g., Remarks, p. 21). The only difference between Nagy and instant application is that Nagy is silent on CLEC2D. Braud teaches CLEC2D is used to transfect graft cells to reduce NK cell killing. Thus, one of ordinary skill in the art would have had a reason to combine Braud’s suggestion (i.e., expressing CLEC2D) in Nagy’s stem cells.
Furthermore, regarding Braud transfecting cell lines but not stem cells, as first matter, Applicant is reminded that a 35 U.S.C. § 103 based test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). As discussed above, Nagy has taught modifying stem cells by transgenes for immune invasion, and Braud is used to teach CLEC2D as a transgene for reducing NK cell killing. Additionally, Braud suggests that expression of LLT1 (i.e., CLEC2D) in graft cells, such as porcine endothelial cells in case of porcine xenotransplantation, may directly protect sensitive graft cells from human NK cell-mediated xenogeneic cytotoxicity ([0063]) and teaches the method is used for the prevention or the treatment of organ and bone marrow transplantation rejection (see e.g., reference claims 54-57). Thus, Braud suggests expressing CLEC2D in graft cells, including bone marrow cells in case of bone marrow transplantation, may protect graft cells from NK cell killing to prevent rejection. Since one of ordinary skill in the art would immediately understand that bone marrow is enriched with hematopoietic stem cells (that is the reason for transplanting bone marrow), Braud indeed suggests expressing CLEC2D in stem cells.
Applicant further argues that (2) neither Nagy or Braud provides any basis to predict whether CLEC2D expression is compatible with stem cell functions, such as self-renewal and differentiation (Remarks, p. 19-20).
Applicant’s arguments have been fully considered but they are not persuasive.
As stated supra, Braud suggests that expression of LLT1 (i.e., CLEC2D) in graft cells protects sensitive graft cells from human NK cell-mediated cytotoxicity ([0063]) and teaches the method is used for the prevention of organ and bone marrow transplantation rejection (see e.g., reference claims 54-57). One of ordinary skill in the art would immediately understand that bone marrow is enriched with hematopoietic stem cells. Thus, Braud indeed suggests expressing CLEC2D in transplanted bone marrow that comprises hematopoietic stem cells and thus CLEC2D expression is likely compatible with stem cell function.
Furthermore, in order to complete the art of record and rebut Applicant's arguments, Reference Rossbach et al., (Human iPSC-Derived Renal Cells Change Their Immunogenic Properties during Maturation: Implications for Regenerative Therapies. Cells. 2022 April, 11, 1328. P. 1-21) regarding CLEC2D expression in stem cells has been cited. Rossbach evidences that CLEC2D is expressed in human induced pluripotent stem cells (hiPSCs) (see e.g., p. 14, end of para 1 and in Fig 6a, row 9 in the heatmap of transcriptome analysis), thus Rossbach evidences that it was well-known before the filing date of the claimed invention that CLEC2D is expressed in hiPSCs and thus CLEC2D expression is compatible with stem cell functions.
Applicant further argues that (3) Nagy’s data is evidence of high unpredictability because Nagy’s clones require expression of all eight transgenes (including SERPIN B9, also known as SPI6) at extraordinarily high levels (among the top 5% expressed genes of all genes) (Remarks, p. 20-22).
Applicant’s arguments have been fully considered but they are not persuasive.
As discussed above, Nagy has taught modifying stem cells by transgenes for immune invasion, and Braud suggests using CLEC2D as a transgene for reducing NK cell killing in graft cells including bone marrow cells. The fact that Nagy has done extensive experimentation with various transgene combinations to achieve stem cell immune evasion by highly expressing all eight transgenes, does not dissuade one of ordinary skill in the art to have combined a CLEC2D transgene as suggested by Braud to that combination to improve the stem cell immune invasion. Furthermore, as Braud teaches LLT1 (CLEC2D) functions by its interacting with CD161 to modulate the activity of cells of the immune system (e.g., [0007]-[0008]), one of ordinary skill in the art would have had a reasonable expectation of success in combining CLEC2D with other transgenes of Nagy since they function through different pathways.
Applicant further argues that (4) no motivation to combine because Braud disclosed CLEC2D before Nagy, yet Nagy failed to include CLEC2D in its extensive evaluation and thus combining Nagy and Braud is hindsight (Remarks, p. 22).
Applicant’s arguments have been fully considered but they are not persuasive.
As a first matter, Nagy’s failure to include Braud’s disclosure of CLEC2D in its evaluation does not dissuade one of ordinary skill in the art to have combined a CLEC2D transgene as suggested by Braud to the transgenes of Nagy to improve the stem cell immune invasion.
In response to applicant's argument that the combination is based upon a hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was filed, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, as discussed above, Nagy has taught modifying stem cells by transgenes for immune invasion, and Braud suggests using CLEC2D as a transgene for reducing NK cell killing in graft cells including bone marrow cells. Accordingly, one of ordinary skill in the art would have had a reason to combine a CLEC2D transgene as suggested by Braud to the transgenes of Nagy to improve the stem cell immune invasion.
Applicant finally argues that (5) unexpected results shown in instant Examples 5 and 6 that successful immune evasion in stem cells was achieved with only two transgenes, contrary to Nagy’s eight transgenes expressed at extraordinary high levels (Remarks, p. 22-23).
Applicant’s arguments have been fully considered but they are not persuasive.
MPEP 716.02(d) states that unexpected results must be commensurate in scope with the claimed invention. In the instant case, the purported unexpected results presented by the Applicant in Examples 5 and 6 were studies performed in iPSCs engineered to express only two transgenes of CLEC2D+SERPINB9 or CLEC2D+TRAIL that are integrated into GAPDH locus driven by a GAPDH promoter in combination with a B2M knockout (see e.g., [00267]-[00269] and Figs 6-7 in Example 5 and see [00271]-[00273] and Fig 8 in Example 6), which is not commensurate in scope with the claimed genetically modified any stem cell comprising heterologous nucleic acids encoding a CLEC2D and a SERPINB9 that are integrated into any locus driven by any promoter and further comprising any number of transgenes and without a B2M knockout.
In summary, Applicant’s arguments are not persuasive.
Claims 6-7 stand rejected under 35 U.S.C. 103 as being unpatentable over Nagy et al., (WO 2018/227286 A1. Prior art of record) in view of Braud et al., (US 2009/0074756A1. Prior art of record) and NCBI alignment (NCBI TNFSF10 alignment with SEQ ID NO: 4. P. 1-5. Prior art of record), as applied to claim 1 above, and further in view of Elefanty et al (WO 2016/074016 A1. Prior art of record).
Claims 6-7 are directed to expression of the heterologous CLEC2D being driven by a promoter of an endogenous GAPDH gene.
However, although Nagy teaches the transgenes are linked to a constitutive promoter such as a CMV promoter (p. 15, line 31-32), Nagy, Braud and NCBI are silent on CLEC2D being driven by a promoter of an endogenous GAPDH gene.
Elefanty teaches targeted integration of exogenous nucleic acids into the locus of a constitutively expressed gene such as GAPDH gene (abstract and Fig 1). Elefanty teaches replacing the genomic stop codon of the constitutively expressed gene with an in-frame translation interruption-reinitiation signal that operably links the constitutively expressed gene with the exogenous nucleic acid (i.e., the exogenous nucleic acid is driven by the promoter of the endogenous constitutively-expressed gene GAPDH gene, see p. 7, lines 24-26 and Fig 1), related to claims 6 and 7. Elefanty teaches experiments with GT-GFP (exogenous GFP being targeted integrated into GAPDH locus and being driven by endogenous GAPDH promoter, see Fig 1) hESCs indicated that this line maintained robust GFP expression when cells were differentiated into hematopoietic mesoderm and endothelial-like cells. Cells comprising this vector also generated neural, cardiomyocyte and pancreatic cell types that retained high levels of reporter expression (p. 39, last para).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the genetically modified stem cell comprising heterologous CLEC2D and SERPINB9 suggested by Nagy in view of Braud and NCBI, by substituting the CMV promoter with a promoter of an endogenous GAPDH gene as suggested by Elefanty with a reasonable expectation of success. Since Nagy aims to link the heterologous nucleic acids to a constitutive promoter (p. 15, line 31-32), and since Elefanty teaches hESCs comprising exogenous GFP driven by endogenous GAPDH promoter maintain robust GFP expression when cells are differentiated into hematopoietic mesoderm, endothelial-like cells, neural, cardiomyocyte and pancreatic cell types (p. 39, last para), one of ordinary skill in the art would have had a reason to targeted integrate the heterologous CLEC2D and SERPINB9 nucleic acids into the endogenous GAPDH locus as suggested by Elefanty in order to achieve constitutive robust expression of the CLEC2D product during multiple generations and differentiation.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 10/21/2025 are acknowledged and have been discussed above.
Claims 10-13 stand rejected under 35 U.S.C. 103 as being unpatentable over Nagy et al., (WO 2018/227286 A1. Prior art of record) in view of Braud et al., (US 2009/0074756A1. Prior art of record) and NCBI alignment (NCBI TNFSF10 alignment with SEQ ID NO: 4. P. 1-5. Prior art of record), as applied to claim 1 above, and further in view of Schrepfer (WO 2023/019226 A1. Cited in IDS 06/30/2025).
With respect to claim 13, as stated supra, Nagy, in view of Braud and NCBI alignment, makes obvious a genetically modified stem cell comprising the heterologous nucleic acid sequence encoding CLEC2D comprising the amino acid sequence at least 95% identical to SEQ ID NO: 2, the heterologous nucleic acid sequence encoding SERPINB9 comprising the amino acid sequence at least 95% identical to SEQ ID NO: 6, a third heterologous nucleic acid sequence encoding TRAIL comprising an amino acid sequence at least 95% identical to SEQ ID NO: 4.
However, Nagy, in view of Braud and NCBI alignment, are silent on the genetically modified stem cell further comprising a genetic modification that results in reduced T cell-mediated killing as compared to a wild-type stem cell in claims 10 and 13 (iv), nor teach the genetic modification comprising a deletion of a B2M gene and a deletion of a CIITA gene in claims 11 and 12.
Schrepfer teaches genetically modified cells for allogeneic cell therapy that avoid detection by the recipient's immune system (abstract and [0004]). Schrepfer teaches the engineered cell comprising modifications that increase expression of one or more tolerogenic factors such as SERPINB9 (see e.g., [0005] and [0041]) and reduce expression of one or more MHC class I molecules such as B2M knocked out ([0011]-[0017]) and one or more MHC class II molecules such as CIITA knocked out ([0026]-[0032]), related to claims 11 and 12. Schrepfer teaches the engineered cells (hypoimmunogenic cells) are protected from T cell-mediated adaptive immune rejection (e.g., [0354] and [0327]), thus teaches the genetic modifications result in reduced T cell-mediated killing as compared to a wild-type stem cell, related to claims 10 and 13 (iv).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the genetically modified stem cell comprising heterologous CLEC2D, SERPINB9 and TRAIL suggested by Nagy in view of Braud and NCBI, by combining genetic modifications comprising deletion of B2M gene and CIITA gene resulting in reduced T cell-mediated killing as suggested by Schrepfer with a reasonable expectation of success. Since both Nagy and Braud aim to enhance allograft tolerance (see above), and since Schrepfer teaches genetically modified cells comprising deletion of B2M gene and CIITA gene are protected from T cell-mediated adaptive immune rejection (e.g., [0354] and [0327]), one of ordinary skill in the art would have had a reason to combine genetic modifications comprising deletion of B2M gene and CIITA gene as suggested by Schrepfer in order to protect the stem cell from T cell-mediated adaptive immune rejection to enhance allograft tolerance.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 10/21/2025 are acknowledged and have been discussed above.
Maintained Provisional Double Patenting Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2 and 6-13 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims 30-43 of copending Application No. 19/073,872 (‘872). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims of ‘872 recite an engineered stem cell (ref. claims 30 and 39) comprising at least two heterologous nucleic acid sequences each encoding a polypeptide that is expressed sufficiently to inhibit immune cell mediated cytotoxicity, the polypeptides comprising CLEC2D, SERPINB9 and TRAIL comprising an amino acid sequence at least 95% identical to SEQ ID NO: 2, 4, or 6 (ref claims 30-35), the heterologous nucleic acid sequences being integrated into sustained transgene expression locus comprising a locus within GAPDH gene (ref. claim 36), the engineered cell further comprising a genetic modification that results in reduced T cell mediated killing comprising a deletion of B2M gene and a deletion of CIITA gene (ref. claim 38), the engineered cell being a human cell (ref. claim 41) and a population of engineered cells comprising a cardiac cell, a neural cell or an endothelial cell that are derived from the engineered cell (ref. claim 40 and 42, indicating the pluripotency of the engineered stem cell of reference claim 41), the engineered cell being at least 20% less susceptible to natural killer mediated cytotoxicity (ref. claim 43).
The difference between the cited application claims and the instant claims lies in the fact that the cited application claims are much more specific. Thus the invention of said claims of the cited application are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited application claims, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Response to Traversal:
Applicant’s arguments filed on 10/21/2025 are acknowledged.
Applicant requests that the double patenting rejections be held in abeyance until allowable claims are determined (Remarks, p. 23-24). This is not found persuasive therefore the rejections are maintained. Applicant is reminded that a complete response to a nonstatutory double patenting (NSDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims, or the filing of a terminal disclaimer. Such a response is required even when the nonstatutory double patenting rejection is provisional. See MPEP 804.I.B.1.
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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 Douglas (Doug) Schultz can be reached on (571) 272-0763. 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.
/JIANJIAN ZHU/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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