DETAILED ACTION
This action is in reply to papers filed 02/03/2026.
Claims 1, 3, and 5-10 are pending and examined herein.
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 .
Election/Restrictions
Applicant elected without traverse Group I, drawn to claims 1-10, and the species of “human lymphocyte comprising a polynucleotide encoding an engineered hoCD122” in claim 1, in the reply filed on 08/19/2025. Claims 11-12 and 33-37 are withdrawn from consideration as being drawn to a non-elected invention.
Withdrawn Objection(s) and Rejection(s)
The objection to the disclosure regarding the lack of sequence identifiers in Table 3 and FIG. 1 is withdrawn in light of the substitute specification filed with the appropriate corrections.
The objections to claims 1 and 5-6 regarding informalities are withdrawn in light of the amendment to the claims.
The provisional rejection of claims 1, 3, 5-8, and 10 on the ground of nonstatutory double patenting over claims 3 and 5-7 of copending Application No. 17/916,974, in view of Garcia (US 2019/0183933 Al) and Schumann (PNAS, 2015, 112(33): 10437-10442), is withdrawn because copending Application No. 17/916,974 has been abandoned.
The cancellation of claims 2 and 4 renders any rejections thereof moot.
Claim Interpretation
Claim 1 recites the phrase “an engineered human orthogonal CD122” in line 2. The specification defines “human orthogonal CD122” as a variant of the wildtype CD122 polypeptide that specifically binds to an orthogonal human IL2 (p 28, para 73).
The specification defines “native” as an amino acid sequence or a nucleotide sequence that is found in nature, including allelic variations (p 40, para 92).
These definitions are used for the purposes of examination.
New Grounds of Rejections, Necessitated by Amendment
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 3 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 3 is drawn to “The human lymphocyte or myeloid cell of claim 1, wherein the hoCD122 is modified at one or more residues selected from R41, R42, Q70, K71, T73, T74, V75, S132, H133, Yl34, Fl35, El36, and Q214 relative to native human CD122.” However, amended claim 1 requires the limitation that the engineered hoCD122 comprises a substitution at H133 and Yl34 relative to native human CD122 (lines 2-3). Thus, the cell of claim 3 must, by its dependency on claim 1, comprise modifications in at least two of the residues listed therein (i.e., H133 and Yl34). It is unclear whether the “one or more residues” in claim 3, refer to residues other than H133 and Y134, which has already undergone modification, or whether it includes H133 and Y134, thereby encompassing a cell that is indistinct from the cell of claim 1. Thus, the metes and bounds of claim 3 are unclear.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 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.
Claim 3 is drawn to “The human lymphocyte or myeloid cell of claim 1, wherein the hoCD122 is modified at one or more residues selected from R41, R42, Q70, K71, T73, T74, V75, S132, H133, Yl34, Fl35, El36, and Q214 relative to native human CD122.” Claim 1 requires that the engineered hoCD122 is modified at residues H133 and Yl34 relative to native human CD122. Thus, claim 3 broadens, rather than narrows, the scope of claim 1. 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.
Maintained Rejections
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.
Claim(s) 1, 3, 5-6, and 10 remain rejected under 35 U.S.C. 103 as being unpatentable over Garcia (US 2019/0183933 A1; cited in IDS filed 01/03/2023), in view of Schumann (PNAS, 2015, 112(33): 10437-10442).
Regarding claim 1: Garcia teaches an engineered orthogonal cytokine receptor/ligand pair (para 92), wherein the orthologous receptor is CD122 and the orthologous cytokine is IL-2 (para 99). Garcia further teaches a human T cell (reads on lymphocyte), which has been modified by introduction of an orthologous receptor (para 8, 70, claims 4-5). Garcia teaches that the orthogonal receptor CD122 is modified at one or a combination of positions of H133 and Y134 relative to native human CD122 (para 97-98).
Garcia does not teach an engineered lymphocyte that does not express native human CD122. Garcia teaches that the antibody used to detect CD122 does not differentiate between wildtype CD122 and ortho-CD122 (para 140).
Schumann teaches the use of Cas9 ribonucleoproteins to generate targeted genome modifications in primary T cells (Abstract). Schumann teaches introducing precisely targeted nucleotide replacements in primary T cells by homology-directed repair using Cas9 ribonucleoproteins and exogenous single-stranded DNA templates. Schumann teaches that this method can be used for experimental and therapeutic knock-out and knock-in editing of the genome in primary human T cells.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Garcia by using the method of Schumann to knockout the endogenous CD122 gene and to knock in an engineered hoCD122 in place of the endogenous human CD122 locus. One of ordinary skill in the art would have been motivated to make this modification to eliminate native CD122 signaling that obscures the readout of ortho-CD122 expressed on the cell, since Garcia teaches that the antibody used to detect CD122 does not differentiate between wildtype CD122 and ortho-CD122 (para 140). One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Schumann teaches that the method taught therein can be used to both knockout a gene in primary human T cells and to generate knock-in genome modifications in primary human T cells. Furthermore, Garcia teaches that the cell taught therein may be genetically modified in an ex vivo procedure (para 8).
Regarding claim 3: Following the discussion of claim 1, Garcia teaches that the orthogonal receptor CD122 is modified at one or a combination of positions of R41, R42, Q70, K71, T73, T74, V75, S132, H133, Y134, F135, E136, Q214 relative to native human CD122 (para 97-98).
Regarding claims 5-6: Following the discussion of claim 1, SEQ ID NO: 1 of the instant application is an amino acid sequences consisting of 551 residues, and is the consensus sequence of the wildtype human CD122 transmembrane protein (specification, para 48). CD122 modified at one of this position has 99.8% identity to the sequence set forth in SEQ ID NO: 1. CD122 modified at all 13 positions has 97.6% identity to the sequence set forth in SEQ ID NO: 1 (claim 5). Garcia teaches that the modification may comprise H133D and Y134F (para 98) (claim 6).
Regarding claim 10: The cell taught in Garcia is a human T cell (para 8, 70, claims 4-5).
Claim(s) 1 and 7 remain rejected under 35 U.S.C. 103 as being unpatentable over Garcia (US 2019/0183933 A1), in view of Schumann (PNAS, 2015, 112(33): 10437-10442) and Sockolosky (Science, 2018, 359(6379): 1037-1042; cited in IDS filed 01/03/2023).
The teachings of Garcia and Schumann are set forth above. Garcia, in view of Schumann, renders obvious claim 1.
Regarding claim 7: Garcia does not teach the human lymphocyte of claim 1, wherein the lymphocyte further expresses a CAR.
Sockolosky teaches that the T cells that express orthoIL-2Rβ (reads on ortho CD122) and a CAR has clinical utility (p 5, col 3).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Garcia by utilizing a T cell that also expresses a CAR, as taught in Sockolosky. One of ordinary skill in the art would have been motivated to make this modification because Sockolosky teaches that transduced T cells that express orthoIL-2Rβ and CAR has clinical utility. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Sockolosky teaches that T cells can express both orthoIL-2Rβ and CAR.
Claim(s) 1 and 7-8 remain rejected under 35 U.S.C. 103 as being unpatentable over Garcia (US 2019/0183933 A1), in view of Schumann (PNAS, 2015, 112(33): 10437-10442), Sockolosky (Science, 2018, 359(6379): 1037-1042) and Meissner (US 2016/0348073 A1).
The teachings of Garcia, Schumann, and Sockolosky are set forth above.
Garcia, in view of Schumann, renders obvious claim 1. Garcia, in view of Schumann and Sockosky, renders obvious claim 7.
Regarding claim 8: Garcia, in view of Schumann and Sockolosky, does not teach the human lymphocyte of claim 7, wherein the CAR is selected from the group of CARs recited in instant claim 8.
Meissner teaches that T cells can be genetically modified to express tumor-specific CARs with specificity derived from the variable domains of a monoclonal antibody (para 81). Meissner further teaches that tumor-specific CARs with clinical relevance include CD19, CD20, and CD171 for targeting lymphoma, leukemia, and neuroblastoma (para 148).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Garcia, in view of Schumann and Sockolosky, by expressing CD19, CD20, or CD171 as taught in Meissner. One of ordinary skill in the art would have been motivated to make this modification because Meissner teaches that CAR-T cells expressing CD19, CD20, or CD171 can be used to target lymphoma, leukemia, and neuroblastoma. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Meissner teaches that T cells can be genetically modified to express CD19, CD20, and CD171.
Claim(s) 1 and 9 remain rejected under 35 U.S.C. 103 as being unpatentable over Garcia (US 2019/0183933 A1), in view of Schumann (PNAS, 2015, 112(33): 10437-10442) and Meissner (US 2016/0348073 A1).
The teachings of Garcia and Schumann are set forth above. Garcia, in view of Schumann, renders obvious claim 1.
Regarding claim 9: Garcia, in view of Schumann, does not teach the human lymphocyte of claim 1, wherein the lymphocyte is deleted for one or more of TCRA, TCRB, PD-1, CTLA4, or B2M.
Meissner discloses modified primary human T cells, wherein the CTLA4, PD1, TCRA, TRCB, and/or B2M genes have been deleted to generate an off-the-shelf universal CAR T cell (Abstract; para 5-7). Meissner teaches that the deletion of the aforementioned genes reduces or eliminates the risk of immune rejection or graft-versus-host disease (Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Garcia, in view of Schumann, by deleting one or more of CTLA4, PD1, TCRA, TRCB, and B2M genes, as taught in Meissner. One of ordinary skill in the art would have been motivated to make this modification because Meissner teaches that the deletion of the CTLA4, PD1, TCRA, TRCB, and/or B2M genes reduces or eliminates the risk of immune rejection or graft-versus-host disease. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Meissner teaches that CTLA4, PD1, TCRA, TRCB, and/or B2M genes can be deleted from human T cells.
Claim(s) 1, 3, 5-7, and 10 remain rejected under 35 U.S.C. 103 as being unpatentable over Sockolosky (Science, 2018, 359(6379): 1037-1042), in view of Garcia (US 2019/0183933 A1) and Schumann (PNAS, 2015, 112(33): 10437-10442).
Regarding claims 1 and 10: Sockolosky teaches an engineered orthogonal cytokine receptor/ligand pair, wherein the orthologous receptor is CD122 and the orthologous cytokine is IL-2 (Abstract). Sockolosky further teaches a mouse T cell (reads on lymphocyte), which has been modified by introduction of an orthologous CD122 (Fig. 3; p 3, col 1-2).
Sockolosky does not teach a human lymphocyte comprising a polynucleotide encoding an engineered hoCD122.
Garcia teaches a T cell (reads on lymphocyte), which has been modified by introduction of an orthologous CD122 (para 8, 70, 99; claims 4-5). Garcia teaches that the orthogonal receptor CD122 is modified at one or a combination of positions of H133 and Y134 relative to native human CD122 (para 97-98). Garcia teaches that the T cell may be a mouse or human cell (para 8, 70, claims 4-5).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Sockolosky by using a human T cell instead of a mouse cell. One of ordinary skill in the art would have been motivated to make this modification to obtain an engineered T cell for human therapeutics. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Garcia teaches that both mouse and human T cells can be modified by introduction of an orthologous CD122.
Sockolosky, in view of Garcia, does not teach a human lymphocyte that does not express native human CD122.
Schumann teaches the use of Cas9 ribonucleoproteins to generate targeted genome modifications in primary T cells (Abstract). Schumann teaches introducing precisely targeted nucleotide replacements in primary T cells by homology-directed repair using Cas9 ribonucleoproteins and exogenous single-stranded DNA templates. Schumann teaches that this method can be used for experimental and therapeutic knock-out and knock-in editing of the genome in primary human T cells.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Sockolosky, in view of Garcia, by using the method of Schumann to knockout the endogenous CD122 gene and to knock in an engineered hoCD122 in place of the endogenous human CD122 locus. One of ordinary skill in the art would have been motivated to make this modification to eliminate native CD122 signaling that obscures the readout of ortho-CD122 expressed on the cell, since Garcia teaches that the antibody used to detect CD122 does not differentiate between wildtype CD122 and ortho-CD122 (para 140). One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Schumann teaches that the method taught therein can be used to both knockout a gene in primary human T cells and to generate knock-in genome modifications in primary human T cells. Furthermore, Garcia teaches that the cell taught therein may be genetically modified in an ex vivo procedure (para 8).
Regarding claims 3 and 5-6: Following the discussion of claim 1, Garcia teaches that the orthogonal receptor CD122 is modified at one or a combination of positions of R41, R42, Q70, K71, T73, T74, V75, S132, H133, Y134, F135, E136, Q214 relative to native human CD122 (para 97-98) (claim 3). SEQ ID NO: 1 of the instant application is an amino acid sequences consisting of 551 residues, and is the consensus sequence of the wildtype human CD122 transmembrane protein (specification, para 48). CD122 modified at one of this position has 99.8% identity to the sequence set forth in SEQ ID NO: 1. CD122 modified at all 13 positions has 97.6% identity to the sequence set forth in SEQ ID NO: 1 (claim 5). Garcia teaches that the modification may comprise H133D and Y134F (para 98) (claim 6).
Regarding claim 7: Sockolosky does not reduce to practice the human lymphocyte of claim 1, wherein the lymphocyte further expresses a CAR. However, Sockolosky teaches that the T cells that express orthoIL-2Rβ (reads on ortho CD122) and a CAR has clinical utility (p 5, col 3).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Sockolosky, in view of Garcia and Schumann, by utilizing a T cell that also expresses a CAR, as taught in Sockolosky. One of ordinary skill in the art would have been motivated to make this modification because Sockolosky teaches that transduced T cells that express orthoIL-2Rβ and CAR has clinical utility. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Sockolosky teaches that T cells can express both orthoIL-2Rβ and CAR.
Claim(s) 1 and 7-9 remain rejected under 35 U.S.C. 103 as being unpatentable over Sockolosky (Science, 2018, 359(6379): 1037-1042), in view of Garcia (US 2019/0183933 A1), Schumann (PNAS, 2015, 112(33): 10437-10442), and Meissner (US 2016/0348073 A1).
The teachings of Sockolosky, Garcia, and Schumann are set forth above.
Sockolosky, in view of Garcia and Schumann, renders obvious claims 1 and 7.
Regarding claim 8: Sockolosky, in view of Garcia and Schumann, does not teach the human lymphocyte of claim 7, wherein the CAR is selected from the group of CARs recited in claim 8.
Meissner teaches that T cells can be genetically modified to express tumor-specific CARs with specificity derived from the variable domains of a monoclonal antibody (para 81). Meissner further teaches that tumor-specific CARs with clinical relevance include CD19, CD20, and CD171 for targeting lymphoma, leukemia, and neuroblastoma (para 148).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Sockolosky, in view of Garcia and Schumann, by expressing CD19, CD20, or CD171 as taught in Meissner. One of ordinary skill in the art would have been motivated to make this modification because Meissner teaches that CAR-T cells expressing CD19, CD20, or CD171 can be used to target lymphoma, leukemia, and neuroblastoma. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Meissner teaches that T cells can be genetically modified to express CD19, CD20, and CD171.
Regarding claim 9: Sockolosky, in view of Garcia and Schumann, does not teach the human lymphocyte of claim 1, where in the lymphocyte is deleted for one or more of TCRA, TCRB, PD-1, CTLA4, or B2M.
Meissner discloses modified primary human T cells, wherein the CTLA4, PD1, TCRA, TRCB, and/or B2M genes have been deleted to generate an off-the-shelf universal CAR T cell (Abstract; para 5-7). Meissner teaches that the deletion of the aforementioned genes reduces or eliminates the risk of immune rejection or graft-versus-host disease (Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Sockolosky, in view of Garcia and Schumann, by deleting one or more of CTLA4, PD1, TCRA, TRCB, and B2M genes, as taught in Meissner. One of ordinary skill in the art would have been motivated to make this modification because Meissner teaches that the deletion of the CTLA4, PD1, TCRA, TRCB, and/or B2M genes reduces or eliminates the risk of immune rejection or graft-versus-host disease. One of ordinary skill in the art would have had a reasonable expectation of making this modification because Meissner teaches that CTLA4, PD1, TCRA, TRCB, and/or B2M genes can be deleted from human T cells.
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, 3, 5-8, and 10 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-4, 6, 12, and 16-18 of copending Application No. 17/783,505 in view of Garcia (US 2019/0183933 A1) and Schumann (PNAS, 2015, 112(33): 10437-10442).
Copending claim 2 is drawn to a polynucleotide encoding a modified human CD122 comprising an orthogonal human 122.
Copending claim 2 does not recite a human lymphocyte comprising a polynucleotide encoding a modified human CD122 comprising an orthogonal human CD122.
Garcia teaches an engineered orthogonal cytokine receptor/ligand pair (para 92), wherein the orthologous receptor is CD122 and the orthologous cytokine is IL-2 (para 99). Garcia further teaches a human T cell (reads on lymphocyte), which has been modified by introduction of an orthologous receptor (para 8, 70, claims 4-5).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the polynucleotide of copending claim 2 by introducing it into a human T cell, as taught in Garcia. One of ordinary skill in the art would have been motivated to make this modification to make a cell comprising said polynucleotide for therapeutics. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Garcia teaches that a polynucleotide encoding a modified human CD122 can be introduced into a human T cell.
Copending claim 2, in view of Garcia, does not disclose an engineered lymphocyte that does not express native human CD122. Schumann cures this deficiency, for the reasons set forth above (Rejections under 35 U.S.C. 103).
Therefore, claims 1 and 10 is rendered obvious over copending claim 2.
Following the discussion above, copending claims 3-4 and 12 render obvious claim 3. SEQ ID NO:1 of the copending application is 100% identical to SEQ ID NO: 1 of the instant application, rendering claims 5-6 obvious over copending claim 6.
Copending claim 16 is drawn to a cell comprising the polynucleotide encoding a modified human CD122. Copending claim 16 does not recite that the cell is a human lymphocyte, or that the modified human CD122 is an orthogonal human CD122.
Garcia teaches an engineered orthogonal cytokine receptor/ligand pair (para 92), wherein the orthologous receptor is CD122 and the orthologous cytokine is IL-2 (para 99). Garcia further teaches a human T cell (reads on lymphocyte), which has been modified by introduction of an orthologous receptor (para 8, 70, claims 4-5).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the cell of copending claim 16 by introducing it into a human T cell, as taught in Garcia. One of ordinary skill in the art would have been motivated to make this modification to make a cell comprising said polynucleotide for therapeutics. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Garcia teaches that a polynucleotide encoding a modified human CD122 can be introduced into a human T cell. Therefore, claims 1 and 10 are rendered obvious over copending claim 16.
Following the discussion above, copending claim 17 renders obvious claim 7, and copending claim 18 renders obvious claim 8.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 5-8, and 10 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2 and 4-5 of copending Application No. 17/758,830 in view of Garcia (US 2019/0183933 A1) and Schumann (PNAS, 2015, 112(33): 10437-10442).
Copending claim 1 is drawn to a method of treating a mammalian subject comprising contacting isolated immune cells of said subject with a nucleic acid sequence encoding an orthogonal hCD122. Copending claim 2 limits the cell of claim 1 to human immune cells including human T cells. Copending 2 does not recite an engineered lymphocyte that does not express native human CD122. Schumann cures this deficiency, for the reasons set forth above on page 6-7 (Rejections under 35 U.S.C. 103). Therefore, the cell of claims 1 and 10 are rendered obvious by the method of copending claim 2.
Following the discussion above, copending claim 4 renders obvious instant claim 3. Copending claim 5 renders obvious claim 7. The amino acid sequence set forth in copending claim 25 is 100% identical to instant SEQ ID NO: 1, rendering claims 3-8 obvious over copending claim 25. Copending claim 29 renders obvious claims 1, 3, 5-8, and 10. Copending claim 37 renders obvious claim 8.
Response to Arguments
Examiner’s note: Any reference cited below is provided solely to rebut Applicant’s arguments.
Rejections of claims 1, 3, 5-6, and 10 under 35 U.S.C. 103 over Garcia (US 2019/0183933 A1), in view of Schumann (PNAS, 2015, 112(33): 10437-10442)
Applicant argues: Applicant disagrees that the Garcia reference taught or suggested that the antibody used to detect CD122 created a motivation to knock out the endogenous CD122 gene. As can be seen in Garcia paragraph 0140, Garcia was able to measure the expression of the orthologous receptor by measuring increased fluorescence intensity. There was no reason to go to the trouble of knocking out the endogenous CD122 gene based on this statement by Garcia. Indeed, Garcia does not mention any concern about the endogenous receptor and states that "[t]his cell line is also positive for CD25 and CD132 and
thus represents T cells expressing the high - affinity IL - 2 receptor complex." There is no indication that endogenous CD122 gene expression was undesirable.
In response: Applicant’s arguments have been fully considered, but are not persuasive. Given that the antibody used by Garcia to detect CD122 does not differentiate between wildtype CD122 and ortho-CD122 (para 140), one of ordinary skill in the art would understand that the elimination of endogenous CD122 gene expression would allow for a more precise readout of ortho-CD122 expressed on the cell. For example, Uhlen (Nature Methods, 2016, 13: 823-827) provides a commentary with five conceptual 'pillars' for antibody validation to be used in an application-specific manner, based on an ad hoc International Working Group for Antibody Validation (p 823, Header). Uhlen teaches that whenever possible, genetic approaches, in which antibody specificity can be assessed by measuring the relevant signal in control cells or tissues in which the target gene or epitope has been knocked out or knocked down using techniques such as CRISPR–Cas9, are powerful because they provide a direct link between the gene, the target protein, and its detection by the antibody (p 824, col 2). Uhlen teaches that the use of genome editing techniques (i.e., such as the technique taught in Schumann) is preferred since they may result in complete loss of protein expression (p 824, col 2). Thus, given Garcia’s disclosure that the antibody used therein to detect CD122 does not differentiate between wildtype CD122 and ortho-CD122 (para 140), one of ordinary skill in the art would understand that there was motivation to knock out endogenous CD122.
Applicant argues: Moreover, the claimed invention is non-obviously advantageous by generating a T-cell that is dependent upon the orthologous IL2 ligand for stimulation. The T-cell described in paragraph 0140 of Garcia also expressed endogenous CD122, and therefore was fully responsive to naturally-occurring IL2. The cell described in Gracia paragraph 0140, when introduced into a human, would respond and replicate in response to simulation from endogenous IL2 as well as from the orthologous IL2 ligand. In contrast, the claimed cell would be unresponsive to natural IL2 and thus would be dependent (addicted) to the orthologous IL2 ligand for stimulation. Thus, introduction of a cell as claimed into a human would be more readily controlled because it would not respond to native IL2 ligand, allowing for decline of the engineered cell populations once the orthologous IL2 ligand was no longer administered to the patient. This aspect was not taught or suggested in the cited art nor does the rejection so argue. While Schumman describes modification of certain genes, Schumann is completely silent with regard to the endogenous IL2 receptor and certainly does not provide a motivation to knock out CD122 in conjunction in the engineered orthogonal human CD122 recited in the claims. Accordingly, the claimed subject matter is non-obvious and withdrawal of the rejection is respectfully requested.
In response: Applicant’s arguments have been fully considered, but are not persuasive. First, the rejection of claims 1-6 and 10 over Garcia, in view of Schumann, is maintained; the human lymphocyte of claims 1-6 and 10 are rendered obvious over Garcia, in view of Schumann, as set forth above.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., that the introduction of a cell as claimed into a human would be more readily controlled because it would not respond to native IL2 ligand, allowing for decline of the engineered cell populations once the orthologous IL2 ligand was no longer administered to the patient) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Rejections of claims 1, 3, 5-8, and 10 on the ground of nonstatutory double patenting over claims 2-4, 6, 12, and 16-18 of copending Application No. 17 /783,505 in view of Garcia and Schumann
Applicant argues: Application No. 17/783,505 has not issued as a patent and thus Applicant requests the rejection be held in abeyance until a patent issues. Moreover, Applicant respectfully requests withdrawal of the rejection for the reasons discussed above with respect to the obviousness rejection based on Garcia and Schumann.
In response: Applicant’s arguments have been fully considered, but are not persuasive. Applicant’s arguments regarding Garcia and Schumann have been addressed above.
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 in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional. As filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance. Only compliance with objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. See MPEP 804 (I)(B)(1).
Rejections of claims 1, 3, 5-8, and 10 on the ground of nonstatutory double patenting over claims 2 and 4-5 of copending Application No. 17/758,830 in view of Garcia and Schumann
Applicant argues: Application No. 17/758,830 has not issued as a patent and thus Applicant requests the rejection be held in abeyance until a patent issues. Moreover, Applicant respectfully requests withdrawal of the rejection for the reasons discussed above with respect to the obviousness rejection based on Garcia and Schumann.
In response: Applicant’s arguments have been fully considered, but are not persuasive. Applicant’s arguments regarding Garcia and Schumann have been addressed above.
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 in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (see MPEP § 1490 for a discussion of terminal disclaimers). Such a response is required even when the nonstatutory double patenting rejection is provisional. As filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance. Only compliance with objections or requirements as to form not necessary for further consideration of the claims may be held in abeyance until allowable subject matter is indicated. 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 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 Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 EST.
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/RISA TAKENAKA/Examiner, Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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