DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s election without traverse of Group I (claims 1, 5-10 and 22-29) and species of (i) EGFR, (ii) CD16 and (iii) a chimeric antigen receptor, IL-15, CD16 and a suicide gene in the reply filed on 7/13/2026 is acknowledged.
3. New claims 98-100 have been added. Claims 1, 5-10, 22-29, 32-34, 36, 38, 67, 69, 82-83, 88-89 and 98-100 are pending. Claims 2-4, 11-21, 30-31, 35, 37, 39-66, 68, 70-81, 84-87 and 90-97 are canceled. Claims 32-34, 36, 38, 67, 69, 82-83, 88-89, 98 and 99 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention/species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/13/2026.
4. Claims 1, 5-10, 22-29 and 100 are under examination.
Information Disclosure Statement
5. The information disclosure statements (IDS) submitted on 9/19/2023, 11/6/2023, 3/20/2025, 2/22/2026, 3/26/2026 and 4/9/2026 have been considered by the examiner.
Priority
6. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 63228991 and 63172402, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Claim 6 is drawn to the composition of claim 1, wherein the complex further comprises the antigen binding domain of the monospecific antibody bound to its target antigen.
Claim 8 is drawn to the composition of claim 1, wherein the one or more antigen binding domain or domains of the antibody is bound to its target antigen.
Application Nos. 63228991 and 63172402 do not disclose a composition comprising:(1) one or more cord blood-derived natural killer (NK) cells; and(2) one or more one antibody molecules, wherein
(a) the antibody is monospecific, wherein an Fc region of the monospecific antibody binds the NK cell and an antigen binding domain of the monospecific antibody is capable of binding a target antigen; or
(b) the antibody is multispecific and one or more antigen binding domains of the antibody binds a target antigen and another antigen binding domain or domains of the antibody is capable of binding an NK cell surface antigen, and
wherein the antigen binding domain of the monospecific antibody bound to its target antigen, or
wherein the one or more antigen binding domain or domains of the antibody is bound to its target antigen.
Therefore, the effective filing date of claims 6 and 8 is the filing date of PCT/US2022/023920 (i.e. 4/7/2022).
Claim Objections
7. Claims 1, 5-10, 22-29 and 100 are objected to because of the following informalities:
Claim 1 is objected to for a typographical error, see “one or more one antibody molecules” in line 3.
Claim 1 is objected to for reciting “one or more antibody molecules” in line 3, and “the antibody” in lines 4 and 7. It is unclear if “the antibody” refers to the one antibody molecule or one of the more than one antibody molecules. Claim 100 is objected to for the same reasons.
Claims 1, 5-10, 22-29 and 100 are objected to for a grammatical error. The verb (e.g. bind) after the phrase “one or more antigen binding domains” should be in plural form. see claims 1 and 7-8, for example.
Claim 9 is objected to for reciting “wherein the target antigen is ….a combination thereof”. A target antigen is one antigen. However, a combination is more than one antigen. Similarly, claim 23 is objected to for reciting “wherein the engineered antigen receptor is …both”.
Claim 23 is objected to for reciting “wherein the engineered receptor”. Claims 23 depends from claim 22. Claim 22 recites “one or more engineered receptors”.
Claims 27 and 28 are objected to for reciting “wherein the receptor”. Claims 27 and 28 depend from claim 26. Claim 26 recites “one or more receptors”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 6-7 are 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 6 recites the limitation "the complex" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 6 depends on claim 1. Claim 1 does not mention a complex.
Claim 7 recites “the NK cell surface antigen or antigens” in line 3-4. There is insufficient antecedent basis for “the NK cell surface antigens” in the claim. Claim 7 depends on claim 1. Claim 1 only recites “an NK cell surface antigen”.
Claim Rejections - 35 USC § 102
10. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
11. Claims 1, 5, 6 and 8-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Henno et al. (WO 2017/042393A1, pub. date: 3/16/2017, IDS filed on 9/19/2023).
Regarding claim 1, Henno et al. discloses a pharmaceutical composition comprising cord blood NK (CB NK) cells and a therapeutic antibody, wherein the therapeutic antibody is binding at the surface of the NK cells via the binding between its Fc portion and the CD16 receptor on the surface of the NK cells (pages 5-6), wherein the therapeutic antibody is a monospecific antibody (page 6) or a multispecific antibody (page 7, line 2).
Regarding claim 5, Henno et al teaches that the therapeutic antibody is binding at the surface of the NK cells via the binding between its Fc portion and the CD16 receptor on the surface of the NK cells (page 6, lines 29-31).
Regarding claims 6 and 8, Henno et al. teaches a combination (composition) comprising cord blood NK cells, a therapeutic antibody (rituximab) and lymphoma cells expressing a target antigen (CD20) (page 44). In this combination, the therapeutic antibody binds CD16 expressed on the surface of NK cells via Fc portion, and CD20 on the lymphoma cells via antibody binding domain.
Regarding claim 9, Henno et al. teaches that the therapeutic antibody is an anti-EGFR antibody (page 6, line 17).
Regarding claim 10, Henno et al. teaches that the NK cell surface antigen is CD16 (page 6, line 30).
12. Claims 1 and 6-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kerbauy et al. (Blood, 2018, 132 (supplemental 1): 341, IDS filed on 3/20/2025).
Regarding claims 1 and 7, Kerbauy teaches cord blood derived natural killer cells loaded with a tetravalent bispecific antibody construct (AFM13) as off-the-shelf cell therapy for CD30+ malignancies, wherein the bispecific antibody binds CD16A expressed on the surface of NK cells and CD30 expressed on tumor cells (abstract).
Regarding claims 6 and 8, Kerbauy teaches a combination (composition) comprising AFM13-loaded NK cells with CD30+ Karpas-299 cells. In this combination, AFM13 binds CD16A expressed on the surface of NK cells and CD30 expressed on Karpas-299 cells (abstract).
Regarding claim 9, Henno et al. teaches that AFM13 binds CD30 (abstract).
Regarding claim 10 , Henno et al. teaches that AFM13 binds the NK cell surface protein CD16 (page 6, line 30).
Claim Rejections - 35 USC § 103
13. 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.
14. Claims 1, 5-6, 8-10, 22-25, 29 and 100 are rejected under 35 U.S.C. 103 as being unpatentable over Henno et al. (WO 2017/042393A1, pub. date: 3/16/2017, IDS filed on 9/19/2023), in view of Kerbauy et al. (WO 2019/165121A1, pub. date: 8/29/2019, IDS filed on 3/26/2026) and Liu et al (Leukemia, 2018, 32: 520-531).
The teachings of Henno et al. have been set forth above as they apply to claims 1, 5, 6 and 8-10.
Regarding claim 100, Henno et al. teaches that the anti-EGFR antibody is Imgatuzumab (page 47, line 9).
Regarding claims 22-23 and 100, Henno et al. does not teach that the NK cells are engineered to express a chimeric antigen receptor.
Regarding claim 24-25, Henno et al. does not teach that the NK cells are engineered to express IL-15.
Regarding claim 29, Henno et al. does not teach that the NK cells are engineered to express a suicide gene.
Kerbauy et al. teaches engineering NK cells including cord blood NK cells to express a chimeric antigen receptor against tumor targets ([0006], [0012] and [0036]). Kerbary et al. teaches that in some aspects, the CAR comprises IL-15, and in some aspects, the CAR comprises a suicide gene ([0012]). The suicide gene is inducible caspase 9 ([0072]). Kerbary et al. teaches a method of killing cancer cells using the engineered NK cells ([0027]), in some aspects, the NK cells are combined with a therapeutic antibody, wherein the therapeutic antibody is a monoclonal, bispecific antibody, or trispecific antibody such as rituximab ([0021], [0037]), wherein the antibody may bind CD16 or other receptors on NK cells and redirect cells to a target, thus increasing the response against different tumors ([[0037]). Kerbauy et al. teaches that the CAR may be co-expressed with a cytokine, e.g. IL-15 to improve persistence and increase cytotoxicity ([0068], [00106]).
Liu et al. teaches that CB-derived NK cells transduced with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9) demonstrated efficient killing of CD19-expressing cell lines and primary leukemia cells in vitro, with marked prolongation of survival in a xenograft Raji lymphoma murine model (abstract). Liu et al. teaches that IL-15 production by the transduced CB-NK cells critically improved their function, moreover, iC9/CAR.19/IL-15 CB-NK cells were readily eliminated upon pharmacologic activation of the iC9 suicide gene (abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have engineered the cord blood NK cells of Henno to express a CAR in view of Kerbauy. One of ordinary skill in the art would have been motivated to do so for purpose of redirecting the cytotoxicity of NK cells toward specific tumor antigens. One of ordinary skill in the art would have had a reasonable expectation of success because the method of making CAR NK cells were well known in the art as shown by Kerbauy and Liu. Furthermore, Kerbauy teaches that their NK cells including CAR NK cells can be combined with a therapeutic antibody for treating cancer ([0037]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have engineered the cord blood NK cells of Henno to co-express a CAR, IL-15 and a suicide gene in view of Kerbauy and Liu. One of ordinary skill in the art would have been motivated to do so because Kerbary et al. teaches that the CAR may be co-expressed with a cytokine, e.g. IL-15 to improve persistence and increase cytotoxicity ([0068], [00106]), and Liu et al. teaches ectopically produced IL-15 support the survival and proliferation of the CAR CB NK cells and a suicide gene, inducible caspase-9 (iC9), can be pharmacologically activated to eliminate transduced cells (page 1, last para). Furthermore, it was known in the art that including a suicide gene in CAR NK cells is a safety measure designed to allow controlled elimination of the CAR NK cells if they cause unintended side effects or if the therapy needs to be stopped early. One of ordinary skill in the art would have had a reasonable expectation of success because Liu et al. teaches a method of transducing CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9).
15. Claims 1, 5-6, 8-10 and 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Henno et al. (WO 2017/042393A1, pub. date: 3/16/2017, IDS filed on 9/19/2023), in view of Childs et al. (WO 2016/077734A2, pub date: 5/19/2016, IDS filed on 9/19/2023).
The teachings of Henno et al. have been set forth above as they apply to claims 1, 5-6 and 8-10.
Regarding claims 26-28, Henno et al. do not teach engineering NK cells to express CD16 to enhance their binding to an antibody.
Childs et al. teaches modified NK cells obtained by transfecting NK cells with a heterologous nucleic acid molecule encoding a CD16 protein comprising a valine at amino acid 158 (CD16-V158), and a method of treating cancer using a monoclonal antibody that binds a tumor cell, in combination with the CD16-V158 NK cells (page 1, last para). Childs et al teaches that the majority of humans express CD16 which has a relatively low affinity for IgG1 antibodies, however, a single nucleotide polymorphism in the CD16 gene, resulting in an amino acid substitution of valine (V) for phenylalanine (F) at position 158 (F158V) in the mature (processed) form of the protein, is associated with substantially higher affinity for IgG1 antibodies and superior NK cell-mediated ADCC (page 9, lines 18-22). Childs teaches that antibody-based therapies can benefit from the presence of NK cells having known high levels of Fc-binding capacity and cytotoxic activity within the subject (page 13, lines 22-23). Childs teaches that the co-administration of known quantities of exogenous NK cells having a known level of activity, along with an appropriate antibody, can result in more consistent therapeutic effects (page 13, lines 27-29). Childs teaches transfection or transduction of NK cells with a nucleic acid coding for the high affinity CD16 receptor variant (CD16-V158) may improve the outcome in patients treated with any anti-tumor targeting antibody where such an antibody mediates tumor cytotoxicity at least in part by ADCC (page 14, lines 9-12).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have engineered the cord blood NK cells of Henno to express CD16 V158 in view of Childs. One of ordinary skill in the art would have been motivated to do so because Childs teaches that CD16-V158 is associated with substantially higher affinity for IgG1 antibodies and superior NK cell-mediated ADCC (page 9, lines 18-22). One of ordinary skill in the art would have had a reasonable expectation of success because Childs teaches transfection or transduction of NK cells with a nucleic acid coding for the high affinity CD16 receptor variant (CD16-V158) may improve the outcome in patients treated with any anti-tumor targeting antibody where such an antibody mediates tumor cytotoxicity at least in part by ADCC (page 14, lines 9-12).
Double Patenting
16. 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.
17. Claims 1, 5-10, 22-29 and 100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,466,867, in view of Liu et al (Leukemia, 2018, 32: 520-531), and Childs et al. (WO 2016/077734A2, pub date: 5/19/2016, IDS filed on 9/19/2023).
The claims of the patent disclose a method for treating cancer in an individual in need thereof, comprising administering to the individual in need thereof a therapeutically effective amount of ex vivo-combined pre-activated NK cells and a monoclonal, bispecific, or trispecific antibody, wherein the antibody binds an NK cell receptor to redirect the NK cells to a target tumor cell, wherein the NK cell receptor is CD16 or CD56, the NK cells express a chimeric antigen receptor.
The claims of patent do not disclose that the NK cells are cord-blood NK cells, and the NK cells further express a CD15, a suicide gene and/or a CD16 with enhanced binding to the antibody.
The teachings of Liu and Childs have been discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used cord-blood NK cells and engineered the CB NK cells of the patent to co-express a CAR, IL-15 and a suicide gene in view of Liu. One of ordinary skill in the art would have been motivated to do so because Liu et al. teaches ectopically produced IL-15 support the survival and proliferation of the CAR CB NK cells and the suicide gene, inducible caspase-9 (iC9), can be pharmacologically activated to eliminate transduced cells (page 1, last para). Furthermore, it was known in the art that including a suicide gene in CAR NK cells is a safety measure designed to allow controlled elimination of the CAR NK cells if they cause unintended side effects or if the therapy needs to be stopped early. One of ordinary skill in the art would have had a reasonable expectation of success because Liu et al. teaches a method of transducing CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have engineered the CB NK cells of the patent to express CD16 V158 in view of Childs. One of ordinary skill in the art would have been motivated to do so because Childs teaches that CD16-V158 is associated with substantially higher affinity for IgG1 antibodies and superior NK cell-mediated ADCC (page 9, lines 18-22). One of ordinary skill in the art would have had a reasonable expectation of success because Childs teaches transfection or transduction of NK cells with a nucleic acid coding for the high affinity CD16 receptor variant (CD16-V158) may improve the outcome in patients treated with any anti-tumor targeting antibody where such an antibody mediates tumor cytotoxicity at least in part by ADCC (page 14, lines 9-12).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention and one would have been motivated to have further combined the engineered CB NK cells and an antibody with tumor cells in vitro for purpose of studying the anti-tumor effect of the ex vivo-combined engineered CB NK cells and an antibody in view of Liu (page 521, column 2). When the antibody is combined with the NK cells and tumor cells, the antibody would bind NK cells via Fc region and tumor cells via the antigen binding domain.
18. Claims 1, 5-10, 22-29 and 100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 96-126 of copending Application No. 18/290,898 (reference application), in view of Liu et al (Leukemia, 2018, 32: 520-531), and Childs et al. (WO 2016/077734A2, pub date: 5/19/2016, IDS filed on 9/19/2023).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of the copending application disclose a composition, comprising NK cells modified to express CD3, and one or more bispecific or multi-specific antibodies, wherein the bispecific or multi specific antibody comprises an anti-CD3 antibody, wherein the antibody is complexed to the NK cells, wherein the NK cells are modified to express one or more heterologous proteins selected from an engineered antigen receptor, a cytokine, a homing receptor, or a chemokine receptor,
wherein the engineered antigen receptor is a chimeric antigen receptor (CAR) and/or engineered T cell receptor (TCR),
where in the heterologous protein is a cytokine and wherein the cytokine is selected from the group consisting of: (i) IL-15, IL-12, IL-2, IL-18, IL-21, IL-23, IL-7, GMCSF,
wherein the bispecific antibody comprises an antibody that targets a cancer antigen.
The claims of copending application do not disclose that the NK cells are cord-blood NK cells, the NK cells further express a suicide gene or CD16 having enhanced binding to the antibody.
The teachings of Liu and Childs have been discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used cord-blood NK cells and engineered the CB NK cells of the copending application to co-express a CAR, IL-15 and a suicide gene in view of Liu. One of ordinary skill in the art would have been motivated to do so because Liu et al. teaches ectopically produced IL-15 support the survival and proliferation of the CAR CB NK cells and the suicide gene, inducible caspase-9 (iC9), can be pharmacologically activated to eliminate transduced cells (page 1, last para). Furthermore, it was known in the art that including a suicide gene in CAR NK cells is a safety measure designed to allow controlled elimination of the CAR NK cells if they cause unintended side effects or if the therapy needs to be stopped early. One of ordinary skill in the art would have had a reasonable expectation of success because Liu et al. teaches a method of transducing CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have engineered the CB NK cells of the copending application to express CD16 V158 in view of Childs. One of ordinary skill in the art would have been motivated to do so because Childs teaches that CD16-V158 is associated with substantially higher affinity for IgG1 antibodies and superior NK cell-mediated ADCC (page 9, lines 18-22). One of ordinary skill in the art would have had a reasonable expectation of success because Childs teaches transfection or transduction of NK cells with a nucleic acid coding for the high affinity CD16 receptor variant (CD16-V158) may improve the outcome in patients treated with any anti-tumor targeting antibody where such an antibody mediates tumor cytotoxicity at least in part by ADCC (page 14, lines 9-12).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention and one would have been motivated to have further combined the engineered CB NK cells and the bispecific antibody with tumor cells in vitro for purpose of studying the anti-tumor effect of the complex comprising engineered CB NK cells and an antibody in view of Liu (page 521, column 2). When the bispecific antibody is combined with the NK cells and tumor cells, the bispecific antibody would bind CD3 on the surface of NK cells and the tumor antigen on the tumor cells.
19. Claims 1, 5-10, 22-29 and 100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 10-13, 16-17, 22-23, 25-27, 29, 37, 49, 53, 74, 77, 79, 101-102, 105 and 109-110 of copending Application No. 18/693,894 (reference application), in view of Liu et al (Leukemia, 2018, 32: 520-531), and Childs et al. (WO 2016/077734A2, pub date: 5/19/2016, IDS filed on 9/19/2023).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of the copending application disclose an engineered immune cell comprising:(a) a polynucleotide encoding (i) one or more chimeric antigen receptors (CAR) and/or (ii) one or more T-cell receptors (TCR); and (b) an anti-CD20 antibody, or antigen-binding fragment thereof, optionally attached to a surface of the immune cell, wherein the polynucleotide further encodes an additional polypeptide of interest,
wherein the additional polypeptide of interest is a suicide gene, a cytokine, the cytokine is IL-15, IL-2, IL-12, IL-18, IL-21, IL-23, IL-7, or a combination there, .
wherein the immune cell is a NK cell.
The claims of copending application do not disclose that the NK cells are cord-blood NK cells, the NK cells further express a CD16 having enhanced binding to the antibody.
The teachings of Liu and Childs have been discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used cord-blood NK cells and engineered the NK cells of the copending application to express CD16 V158 in view of Childs. One of ordinary skill in the art would have been motivated to do so because Childs teaches that CD16-V158 is associated with substantially higher affinity for IgG1 antibodies and superior NK cell-mediated ADCC (page 9, lines 18-22). One of ordinary skill in the art would have had a reasonable expectation of success because Childs teaches transfection or transduction of NK cells with a nucleic acid coding for the high affinity CD16 receptor variant (CD16-V158) may improve the outcome in patients treated with any anti-tumor targeting antibody where such an antibody mediates tumor cytotoxicity at least in part by ADCC (page 14, lines 9-12).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention and one would have been motivated to have further combined the engineered CB NK cells and an antibody with tumor cells in vitro for purpose of studying the anti-tumor effect of the ex vivo-combined engineered CB NK cells and the anti-CD20 antibody in view of Liu (page 521, column 2). When the antibody is combined with the NK cells and tumor cells, the antibody would bind NK cells via Fc region and CD20 on the surface of tumor cells via the antigen binding domain.
20. Claims 1, 5-10, 22-29 and 100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 263-282 of copending Application No. 18/850,488 (reference application), in view of Liu et al (Leukemia, 2018, 32: 520-531), and Childs et al. (WO 2016/077734A2, pub date: 5/19/2016, IDS filed on 9/19/2023).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of the copending application disclose a composition, comprising:(a) one or more engineered natural killer (NK) cells comprising:(ai) a nucleic acid sequence encoding a CD70 targeting CAR, or a TROP2 targeting CAR, and (b) one or more antibody molecules,
wherein the one or more antibodies bind an antigen such as EGFR,
wherein the one or more antibodies is Imgatuzumab,
wherein the engineered NK cell is further modified to comprise one or more additional transgenes for expression of one or more heterologous proteins, wherein the one or more heterologous proteins comprises one or more engineered receptors, and/or one or more cytokines,
wherein the one or more heterologous cytokine comprises IL-15, IL-21, IL-2, IL-4, IL-7, IL-12, , IL-18, and/or IL-23,
wherein the one or more antibody molecules are incubated with NK cells for formation of a complex
The claims of copending application do not disclose that the NK cells are cord-blood NK cells, the NK cells further express a suicide gene or CD16 having enhanced binding to the antibody.
The teachings of Liu and Childs have been discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used cord-blood NK cells and to have engineered the NK cells of the copending application to co-express a CAR, IL-15 and a suicide gene in view of Liu. One of ordinary skill in the art would have been motivated to do so because Liu et al. teaches ectopically produced IL-15 support the survival and proliferation of the CAR CB NK cells and a suicide gene, inducible caspase-9 (iC9), can be pharmacologically activated to eliminate transduced cells (page 1, last para). Furthermore, it was known in the art that including a suicide gene in CAR NK cells is a safety measure designed to allow controlled elimination of the CAR NK cells if they cause unintended side effects or if the therapy needs to be stopped early. One of ordinary skill in the art would have had a reasonable expectation of success because Liu et al. teaches a method of transducing CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used cord-blood NK cells and engineered the NK cells of the copending application to express CD16 V158 in view of Childs. One of ordinary skill in the art would have been motivated to do so because Childs teaches that CD16-V158 is associated with substantially higher affinity for IgG1 antibodies and superior NK cell-mediated ADCC (page 9, lines 18-22). One of ordinary skill in the art would have had a reasonable expectation of success because Childs teaches transfection or transduction of NK cells with a nucleic acid coding for the high affinity CD16 receptor variant (CD16-V158) may improve the outcome in patients treated with any anti-tumor targeting antibody where such an antibody mediates tumor cytotoxicity at least in part by ADCC (page 14, lines 9-12).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention and one would have been motivated to have further combined the engineered CB NK cells and an antibody with tumor cells in vitro for purpose of studying the anti-tumor effect of the ex vivo-combined engineered CB NK cells and the anti-CD20 antibody in view of Liu (page 521, column 2). When the antibody is combined with the NK cells and tumor cells, the antibody would bind NK cells via Fc region and CD20 on the surface of tumor cells via the antigen binding domain.
21. Claims 1, 5-10, 22-29 and 100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 8, 16-17, 19-21, 42-43, 45, 48, 58-60, 64, 66 and 69 of copending Application No. 18/993,710 (reference application), in view of Liu et al (Leukemia, 2018, 32: 520-531), and Childs et al. (WO 2016/077734A2, pub date: 5/19/2016, IDS filed on 9/19/2023).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of the copending application disclose a composition, comprising engineered NK cells, and one or more monospecific, bispecific, or multi-specific antibodies, wherein the antibody is Imgatuzumab, wherein the NK cells are cultured in the presence of a CD3-CD19 bispecific antibody, wherein the NK cells and the antibody are administered in the same formulation.
The claims of copending application do not disclose that the NK cells are cord-blood NK cells, the NK cells further express a CAR, an IL-15, a suicide gene or CD16 having enhanced binding to the antibody.
The teachings of Liu and Childs have been discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used cord-blood NK cells and to have engineered the NK cells of the copending application to co-express a CAR, IL-15 and a suicide gene in view of Liu. One of ordinary skill in the art would have been motivated to do so because Liu et al. teaches ectopically produced IL-15 support the survival and proliferation of the CAR CB NK cells and a suicide gene, inducible caspase-9 (iC9), can be pharmacologically activated to eliminate transduced cells (page 1, last para). Furthermore, it was known in the art that including a suicide gene in CAR NK cells is a safety measure designed to allow controlled elimination of the CAR NK cells if they cause unintended side effects or if the therapy needs to be stopped early. One of ordinary skill in the art would have had a reasonable expectation of success because Liu et al. teaches a method of transducing CB-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, IL-15 and inducible caspase-9-based suicide gene (iC9).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used cord-blood NK cells and engineered the NK cells of the copending application to express CD16 V158 in view of Childs. One of ordinary skill in the art would have been motivated to do so because Childs teaches that CD16-V158 is associated with substantially higher affinity for IgG1 antibodies and superior NK cell-mediated ADCC (page 9, lines 18-22). One of ordinary skill in the art would have had a reasonable expectation of success because Childs teaches transfection or transduction of NK cells with a nucleic acid coding for the high affinity CD16 receptor variant (CD16-V158) may improve the outcome in patients treated with any anti-tumor targeting antibody where such an antibody mediates tumor cytotoxicity at least in part by ADCC (page 14, lines 9-12).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention and one would have been motivated to have further combined the engineered CB NK cells and an antibody with tumor cells in vitro for purpose of studying the anti-tumor effect of the ex vivo-combined engineered CB NK cells and the anti-CD20 antibody in view of Liu (page 521, column 2). When the antibody is combined with the NK cells and tumor cells, the antibody would bind NK cells via Fc region and CD20 on the surface of tumor cells via the antigen binding domain.
Conclusion
22. No claims are allowed.
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/HONG SANG/Primary Examiner, Art Unit 1646
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