DETAILED ACTION
Receipt of Arguments/Remarks filed on May 18 2026 is acknowledged. Claims 1-117 and 136 were/stand cancelled. Claims 118-119, 121, 128, 133, 135 and 137 were amended. Claims 118-135 and 137 are pending.
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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 18 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections
The amendments to the drawings filed May 18 2026 are partially sufficient to overcome the objection to the drawings. Specifically the objection over Figures 2, 5, 6, 7A and 7B, 8A and 8B, 10A and 10B, 10C, 11B, 11C, 11D, 11F, 11H and 12B is withdrawn as they are of sufficient quality to be read. However, the objection over the other identified figures is maintained below.
The amendments to the specification filed May 18 2026 are sufficient to overcome the objection to the disclosure for nucleotide sequence deficiencies. Figures which contain sequences are now associated with the corresponding SEQ ID NO: in the description of the drawings.
The amendments filed May 18 2026 are sufficient to overcome the objection of claim 119. The claim now recites the full name of the abbreviation the first time it occurs.
The amendments filed May 18 2026 are sufficient to overcome the rejection of claim 136 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. The claim was cancelled rendering the rejection moot.
The amendments filed May 18 2026 are sufficient to overcome the rejection of claim 137 under 35 U.S.C. 102 (a)(1) as being anticipated by Valamehr et al. (USPGPUB No. 20190271005). Valamehr et al. does not expressly teach insertion of a B2M-HLA-E sequence into the B2M gene
The amendments filed May 18 2026 are sufficient to overcome the rejection of claims 118-128 and 132-137 under 35 U.S.C. 103 as being unpatentable over Valamehr et al. (USPGPUB No. 20210015859); the rejection of claims 129-130 under 35 U.S.C. 103 over Valamehr et al. in view of Andre et al. (USPGPUB No. 20200046767); and the rejection of claim 131 under 35 U.S.C. 103 over Valamehr et al. in view of Watkins et al. (USPGPUB No. 20200079867). Valamehr et al. does not expressly teach insertion of a B2M-HLA-E sequence into the B2M gene. Thus, Applicants arguments have been considered and are persuasive in light of the amendments.
New and Modified Objections/Rejections Necessitated by the Amendments filed May 18 2026
Drawings
The drawings are objected to because 37 C.F.R. 1.84 states “Character of lines, numbers, and letters. All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined.”
In the current case, the words in Figure 4, 11E, 11G, 11H and 12A are illegible.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Response to Arguments
Applicants’ arguments filed May 18 2026 have been fully considered but they are not persuasive.
Applicants argue that the replacement sheets are in compliance. Regarding Applicants arguments, while several of the drawings are now sufficient, there are several drawings that are not legible. For example 11H, which is specifically directed to relevant sequences in the B2M-HLA-E repair which is directed to limitation that is now present in the claim, is not legible.
Claim Rejections - 35 USC § 112-failture to further limit
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 134 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 134 claims the immune cell does not comprise a genetically engineered alteration in one or more gene selected from…HLA-E… Page 9 of the specification states that “a genetically engineered alteration” is an increase in expression and/or activity of one mor more genes selected from..HLA-E (page 9, lines 24-26). Claim 134 depends from claim 118 which recites insertion of a B2M-HLA-E sequence. This would increase the expression of HLA-E as it is being inserted. Therefore, claim 134 fails to further limit as it requires the immune cell does not comprise a genetically engineered alteration in one or more genes selected from…HLA-E (emphasis added).
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
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 118-128, 132-135 and 137 are rejected under 35 U.S.C. 103 as being unpatentable over Valamehr et al. (USPGPUB No. 20210015859) in view of Peng et al. (CN110616186A).
Applicant Claims
The instant application claims method of making an engineered immune cell, the method comprising:(a) providing a gene-edited induced pluripotent stem (iPS) cell, wherein the gene-edited iPS cell is generated by: (1) contacting a somatic cell with a ribonucleic acid (RNA) encoding one or more re- programming factors, which results in reprogramming of the somatic cell into an iPS cell, and (2) causing a disruption of a beta-2-microglobulin (B2M) gene in the iPS cell by contacting the iPS cell with a synthetic RNA encoding one or more gene-editing proteins wherein the disruption comprises insertion of a B2M-HLA-E sequence into the B2M gene; and (b) differentiating the gene-edited iPS cell into an immune cell, wherein the immune cell is a lymphoid cell or myeloid cell.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Valamehr et al. is directed to immunotherapeutics using enhanced IPSC derived effector cells. Standard methodologies of cellular reprogramming in which exogenous pluripotency genes are introduced to a somatic cell, expressed and then either silenced or removed from the resulting pluripotent cells (0093). Induced pluripotent stem cells are cells which are produced from differentiated adult, neonatal or fetal cells that have been induced or changed i.e. reprogrammed into cells capable of differentiating into tissues of all three germ or dermal layers (paragraph 0089).
Taught is contacting non-pluripotent cells with one or more reprogramming factors to indicate reprogramming of the non-pluripotent cell. One or more constructs to allow targeted integration at a selected site one or more double stand breaks at a selected site using at least one endonuclease capable of selected site recognition then the cells are culture to allow endogens DNA repair to generate targeted in/dels at the selected site (paragraph 0010; 0228). Reprogram factors may be in the form of polynucleotides (paragraph 0229). Exemplified (example 3) is induced pluripotent cells which were engineered to knock out B2M gene. Taught is transfection with B2m-targeting gRNA pair with a plasmid expressing Cas9 nickase to knock out B2M. Derivative cells are obtained from iPSC differentiation. These derivative cells include NK cells, NKT cells, T cells (paragraph 0017; claim 30; 0071; 0117). Lymphocytes such as T cells and natural killer (NK) cells, are potent anti-tumor effectors that play an important role in innate and adaptive immunity (paragraph 0004). B2M knockout enables allogeneic cell therapies by eliminating the need for MEW (major histocompatibility complex) matching and avoid recognition and killing by host T cells (paragraph 0175). In some embodiment, one or more genetically modalities obtained through genomic insertion, deletion or substitution in the genome of the pluripotent cell to iPSC (paragraph 0253; claim 25; paragraph 0200). Introduced or increased expression in at least on elf HLA-E is taught (paragraph 0018). Taught are targeted integration and/or in/dels (insertions/deletions) at the desired site. In some embodiments the in/del is comprised in one or more endogenous genes including, but not limited to, B2M. Specifically indicating a targeted editing in B2M encoding gene (paragraph 0231).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Valamehr et al. suggest targeted editing in B2M encoding gene and differentiating iPSC cells into lymphoid cells and that reprogramming somatic cells into iPSC is a standard methodology, Valamehr et al. does not teach insertion of a B2M-HLA-E fusion. However, this deficiency is cured by Peng et al.
Peng et al. (wherein a machine translation is utilized) is directed to increasing the allogeneic T cell transplant compatibility of the method and application thereof. Claimed is a method for increasing allogeneic T cell transplant compatibility wherein one of the seps is knocking of a B2M-HLA-E fusion gene at a B2m genomic site (claim 3; Fig. 2). Taught are two technical solutions to meet overcoming allogenic T cell rejection (technical effect 1) and rejection of allogeneic NK cells (technical effect 2)
at the same time, one of which uses lentivirus to transfer B2M-HLA-E fusion gene into B2M gene knockout T cells, so that HLA-ABC protein does not express cell surface and at the same time, HLA-E protein is expressed, and HLA-E protein does not have polymorphism, and HLA-E can inhibit the attack of allogeneic NK cells, thereby avoiding the attack of allogeneic T cells and NK cells at the same time. Another approach uses gene knock-in technology to knock the B2M-HLA-E fusion gene into the B2M gene locus, so that HLA-E is expressed on the cell surface while other class I HLA proteins cannot be displayed on the cell surface (page 12).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claim 118, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Valamehr et al. and Peng et al. and insert (knockin) a B2M-HLA-E sequence into the B2M gene locus. One skilled in the art would have been motivated to insert a B2M-HLA-E sequence into the B2M gene locus in order to overcome allogenic T cell rejection and rejection of allogeneic NK cells as taught by Peng et al. One skilled in the art would have a reasonable expectation of success as Valamehr et al. suggests introducing or increasing expression of HLA-E as well as in/del in B2M.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Valamehr et al. and Peng et al. and contact somatic cells with RNA encoding one or more reprogramming factors in order to form an iPS cell. One skilled in the art would have been motivated to perform this contacting step as Valamehr et al. teaches that this is a standard methodology in forming iPS cells. One skilled in the art would have been motivated to contact the iPS cell with a RNA encoding a sgRNA and Cas protein in order to cause knockout of B2M. One skilled in the art would have been motivated to knockout this gene as Valamehr et al. expressly exemplifies the knockout. Furthermore, removing B2M enables allogeneic cell therapies by eliminating the need for MEW (major histocompatibility complex) matching and avoid recognition and killing by host T cells as taught by Valamehr et al. One skilled in the art would have been motivated to differentiate the iPS cell into an immune cell such as a T cell or NK cell as Valamehr et al. expressly teaches this type of differentiation. Furthermore these cells are potent anti-tumor effectors that play an important role in innate and adaptive immunity as taught by Valamehr et al.
Regarding the claimed steps, Valamehr et al. teaches that the standard methods of cellular reprograming are those in which exogenous pluripotency genes are introduced into a somatic cell. Valamehr et al. teaches contacting non-pluripotent cells (aka somatic cells) with one or reprogramming factors wherein the reprogramming factors may be in the form of polynucleotides (i.e. RNA encoding; paragraph 0109; 0114). This results in reprogramming of the somatic cell into iPSC reading on step (a)(1) of instant claim 118. Regarding step (a)(2), exemplified by Valamehr et al. is transfecting the iPSC with B2M-targeting gRNA paired with Cas9 (i.e. one or more gene-editing proteins). Valamehr et al. suggests introducing or increasing expression in at least one of HLA-E (paragraph 0018). Taught are targeted integration and/or in/dels (insertions/deletions) at the desired site. In some embodiments the in/del is comprised in one or more endogenous genes including, but not limited to, B2M. Specifically indicating a targeted editing in B2M encoding gene (paragraph 0231). Peng et al. teaches insertion of a B2M-HLA-E sequence into the B2M gene locus in order to overcome allogenic T cell rejection and rejection of allogeneic NK cells. Regarding step (b) Valamehr et al. teaches differentiating the iPSC cell into T cells or NK cells (aka lymphoid cell).
Regarding claim 135, the recitation “synthetic” does not structurally distinguish the reprogramming factors recited in Valamehr et al. compared to a non-synthetic version.
Regarding claims 119-120 and 122, derivative cells are obtained from iPSC differentiation. These derivative cells include NK cells, NKT cells, T cells (paragraph 0017; claim 30; 0071; 0117).
Regarding claim 121 and 126-127, Valamehr et al. teaches patient and donor sourced cells (paragraph 0004) and that the subject is a human patient (paragraph 0095). Since the NK cells are intended to be used as anti-tumor effectors, Valamehr et al. suggests human NK cells. Stromal cells include epithelial cells or fibroblasts (paragraph 0132).
Regarding claims 122-125 Valamehr et al. teaches that the iPSC can be differentiated to a specific cell type including any hematopoietic lineage (paragraph 0117). Hematopoietic stem and progenitor cells include macrophages (paragraph 0101). T cells include gamma delta T cells (γδ T cells) (paragraph 0102). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to differentiate the iPSC into any desired hematopoietic cell type. Since Valamehr et al. suggests all the claimed cell types can be obtained from iPSC there is a reasonable expectation of success.
Regarding claims 128 and 132-133, firstly, the comparison in the claim to cells without disruption of the B2M gene. The same disruption is taught by Valamehr et al. and Peng et al., thus the combination of the teachings of Valamehr et al. and Peng et al. would be expected to provide an increase in proliferation rate of differentiating cells, downregulation of MHC class 1 expression and/or activity; reduced or eliminated NK-cell fratricide. "A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim." Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1172 (Fed. Cir. 1993). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."). Note MPEP 2111.04.
In this case, claims 128 and 132-133, use the term "wherein", rather than "whereby", but it is concluded that the terms should be treated the same…the wherein clause does not inform the artisan of how the “contacting”, “disruption" and “differentiating” steps are performed; rather, the wherein clause merely characterizes the results of those steps. Therefore, we determine that the "wherein" clause is not entitled to weight in construing the claim. Nonetheless, Valamehr et al. teaches feeder cells can be used to enhance proliferation capacity (paragraph 0132); Figure 3 shows that the iPSC-derived NK cells represent greater proliferation (paragraph 0298) suggesting claim 128. Valamehr et al. teaches that the iPSC-derived cells comprises one or more inducible suicide gene integrated at one or more desired integration sites comprising beta-2 microglobulin (B2M). In some embodiments, the genome-engineered iPSC-derived cells comprising one or more suicide genes further comprise one or more in/del comprised in one or more endogenous genes associated with immune response regulation and mediation, including, but not limited to, check point genes, endogenous T cell receptor genes, and MHC class I suppressor genes (paragraph 0249) suggesting claim 132. Fig. 5 shows that HLA-G expression rescues B2M null iPSCs from killing by NK cells (paragraph 0039) suggesting claim 133.
Regarding claim 134, as claimed by Valamehr et al. induced or expression of HLA-G, HLA-E, is optional (see claim 2; 0176; 0181). Thus optional knocking in of HLA-G would result in an immune that does not include an engineered alteration in HLA-G. The claim is interpreted as only requiring that one is not genetically altered not that all of them are required to not be altered.
Regarding claim 137, the combination of Valamehr et al. and Peng et al. suggests NK (aka lymphoid) cells with a B2M gene disruption as set forth above. Valamehr et al. teaches a composition for therapeutic use which includes any of the derivative cells (paragraph 0027).
Claims 129-130 are rejected under 35 U.S.C. 103 as being unpatentable over Valamehr et al. (USPGPUB No. 20210015859) in view of Peng et al. (CN110616186A) as applied to claims 118-128, 132-135 and 137 above and in further view of Andre et al. (USPGPUB No. 20200046767).
Applicant Claims
The instant application claims wherein the method further comprises enriching for CD34+ cells. The instant application claims wherein the differentiating comprises differentiating the immune cell into CD5+/CD7+ common lymphoid progenitors.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Valamehr et al. and Peng et al. are set forth above. It is taught that iPSC derived non-pluripotent cells include CD34 cells (paragraph 0007). T lymphocyte/T cells are taught. It is taught that the T cell can be any T cell (paragraph 0102).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Valamehr et al. does not expressly teach enriching CD34 cells or CD5+/CD7+ common lymphoid progenitors. However, this deficiency is cured by Andre et al.
Andre et al. is directed to a method for generating t cells progenitors. Currently, in allograft situations with partial HLA incompatibility, the injections, to previously conditioned recipients, of increasing doses of sorted CD34+ HSPC allows donor transplantation with effective prevention of graft-versus-host disease (GVH) (paragraph 0034). It is important to accelerate the generation of T lymphocytes by the administration of precursors already engaged in the T lymphocyte differentiation pathway (T cell progenitors) (paragraph 0007). These T cell precursors are obtained from CD34+ HSPC differentiation and have in particular the CD7+ marker, which is a marker of differentiation in the T-cell pathway (paragraph 0008). Andre et al. teaches that samples were directly enriched for CD34+ cells (paragraph 0186). Figure 9 shows the percentage and total number of CD5+CD7+ cultured starting with CD34+ (paragraph 0185).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Valamehr et al., Peng et al. and Andre et al. and enrich the cells with CD34+ to allow differentiation to CD5+CD7+ T cells. One skilled in the art would have a reasonable expectation of success as Valamehr et al. teaches that iSPC can be CD34+ cells and any type of T cell and Andre et al. teaches that the CD34+ differentiate into CD5+CD7+ cells.
Claim 131 is rejected under 35 U.S.C. 103 as being unpatentable over Valamehr et al. (USPGPUB No. 20210015859) in view of Peng et al. (CN110616186A) as applied to claims 118-128, 132-135 and 137 above and in further view of Watkins et al. (USPGPUB No. 20200079867).
Applicant Claims
The instant application claims wherein the method yields CD56dim CD 16+ NK cells.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Valamehr et al. and Peng et al. are set forth above. Valamehr et al. teaches iPSC derived cells which are NK cells. Lymphocytes such as T cells and natural killer (NK) cells, are potent anti-tumor effectors that play an important role in innate and adaptive immunity (paragraph 0004).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Valamehr et al. does not expressly teach the NK cells are CD56dim CD 16+ NK cells. However, this deficiency is cured by Watkins et al.
Watkins et al. is directed to compositions and method for enhancing the killing of target cells by NK cells. In humans, NK cells are composed of two distinct populations: CD56dim/CD16pos and CD56bright/CD16neg. In healthy individuals, the CD16neg population represents 5-15% of the total NK cell population. However, in some cancer patients the proportion of CD16neg NK cells is greatly increased (e.g., up to 50%) (paragraph 0092). The tumor micro-environment has been shown to affect the phenotype of CD56dim/CD16pos NK cells by either inducing shedding of CD16A from the surface of the cells (activity mediated by ADAM17 enzyme) or TGFβ can promote conversion from CD16Apos to CD16neg NK cells (paragraph 0093).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Valamehr et al., Peng et al. and Watkins et al. and utilize NK cells that are CD56dim/CD16pos. One skilled in the art would have been motivated to utilize these cell types as there are one of two distinct types of NK cells in humans as taught by Watkins et al. Since Valamehr et al. suggests use as anti-tumor effectors and there is an increase in CD16neg NK cells is increased as taught by Watkins et al., one skilled in the art would have been motivated to utilize NK cells that are CD56dim/CD16pos when treating cancer.
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.
Claim 137 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 79 of copending Application No. 18861162. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant application claims composition comprising an isolated immune cell comprising a genetically engineered disruption in a beta-2-microglobulin (B2M) gene, wherein the disruption comprises insertion of a B2M-HLA-E sequence into the B2M gene, wherein the immune cell is selected from a lymphoid cell or myeloid cell.
Regarding claim 137, copending ‘162 claims an engineered cell comprising a disruption in a B2M gene, wherein the engineered cell expresses a fusion protein comprising a fragment of a B2M polypeptide and a HLA-E polypeptide (claim 79).
Response to Arguments
Applicant's arguments filed May 18 2026 are acknowledged. The rejections are maintained since applicant has not made any substantive arguments traversing the rejection.
Applicant(s) is/are reminded that a request to hold a rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an OBJECTION or REQUIREMENTS AS TO FORM (see MPEP 714.02 and CFR 1.111(b)).
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 ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm 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, Neil Hammell can be reached at 571-270-5919. 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.
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
Prosecution Insights