DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in the instant application on 10/04/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/18/2026, 03/02/2026, 01/26/2026, 01/10/2025, 11/27/2024, and 12/08/2025 are being considered by the examiner. The signed IDS forms are attached with the instant office action.
Election/Restrictions
Applicant’s election without traverse of Group I and the species of head and neck squamous cell carcinoma (HNSCC) in the reply filed on 06/18/2026 is acknowledged.
Claims 48-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/18/2026.
Claims 1-4, 9-11, 19, 26, 32 and 43-47 are being examined on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 46 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. The claim recites “wherein the natural killer cells are derived from the same umbilical cord blood donor” and it is unclear as to who the donor is. The claim from which it depends does not require an umbilical cord blood donor and therefore the limitation lacks antecedent basis and is indefinite as it is confusing as to who the donor is.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claims 1-2, 9, 19, 26, 43-45, and 47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Guy Dipierro and Gary Dos Santos (from IDS filed 11/27/2024, WO2019222293A1) and as supporting evidence Elisa Cisneros et. al. (from IDS filed 11/27/2024, Haplotype-Based Analysis of KIR-Gene Profiles in a South European Population—Distribution of Standard and Variant Haplotypes, and Identification of Novel Recombinant Structures, Front Immunol, 2020 Mar 17;11:440).
Regarding claims 1-2, 9, Dipierro discloses a method of treating a disease or condition, wherein the condition is cancer by administering a composition comprising allogenic NK cells and an antibody targeting EGFR (see claim 43 and 50) such as cetuximab (Erbitux) for head and neck squamous cell carcinoma (see 0132), and (see 0139: numbers 46-48, 57, 60), and wherein NK cells are positive for KIR2DL2/3 (see 0008), and homozygous for CD16 158V polymorphism (see 0075).
Regarding claim 19, DIpierro discloses administering IL-2 (see 0017).
Regarding claim 26, Dipierro does not disclose or require that the NK cells be genetically modified.
Regarding claim 43, Dipierro does not disclose or require that the NK cells comprise of a CD16 transgene.
Regarding claim 44, Dipierro does not disclose or require that the NK cells express an exogenous CD16 protein.
Regarding claim 45, Dipierro does not disclose or require that the NK cells are not genetically engineered.
Regarding claim 47, Dipierro discloses “in some embodiments, the isolated cells are cultured to achieve a therapeutically effective amount of the NK cells or subset thereof. In some embodiments, the isolated cells are cultured to achieve a number of enriched NK cells or subset thereof from or from about 105 to about 1012 cells, from or from about 105 to about 108 cells, from or from about 106 to about 1012 cells, from or from about 108 to about 1011 cells, or from or from about 109 to about 1010 cells” (see 0018).
Cisnerso teaches “Restriction-fragment length polymorphism studies published in 1997 sorted KIR genotypes into categories “A” and “B,” based on variable presence of a 24 Kbp-long HindIII band, later shown to derive from the KIR2DL5 gene (11, 12). This definition was then refined and adapted (13), so that “A haplotype” now officially designates a nearly fixed combination of seven genes and pseudogenes, encoding the HLA-C-specific KIR 2DL3 and 2DL1 in the variable centromeric interval, and 3DL1 and 2DS4 in the telomeric one. In contrast, “B” designates collectively a vast array of haplotypes bearing any additional KIR gene (even when they also have, as it often happens, parts of an A haplotype)” (see para. 5). Thus, it is appreciated that the haplotype KIR2DL2/3 discussed by Dipierro is considered KIR-B.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 9-11, 19, 26, 32 and 43-47 are rejected under 35 U.S.C. 103 as being unpatentable over Guy Dipierro and Gary Dos Santos (from IDS filed 11/27/2024, WO2019222293A1) and as supporting evidence Elisa Cisneros et. al. (Haplotype-Based Analysis of KIR-Gene Profiles in a South European Population—Distribution of Standard and Variant Haplotypes, and Identification of Novel Recombinant Structures, Front Immunol, 2020 Mar 17;11:440) and Laurent Boissel et. al. (Umbilical Cord Mesenchymal Stem Cells Increase Expansion of Cord Blood Natural Killer Cells, Biology of Blood and Marrow Transplantation, Volume 14, Issue 9, September 2008, 1031-1038).
Regarding claims 1-2, 9, Dipierro discloses a method of treating a disease or condition, wherein the condition is cancer by administering a composition comprising allogenic NK cells and an antibody targeting EGFR (see claim 43 and 50) such as cetuximab (Erbitux) for head and neck squamous cell carcinoma (see 0132), and (see 0139: numbers 46-48, 57, 60), and wherein NK cells are positive for KIR2DL2/3 (see 0008), and homozygous for CD16 158V polymorphism (see 0075).
Regarding claim 19, DIpierro discloses administering IL-2 (see 0017).
Regarding claim 26, Dipierro does not disclose or require that the NK cells be genetically modified.
Regarding claim 43, Dipierro does not disclose or require that the NK cells comprise of a CD16 transgene.
Regarding claim 44, Dipierro does not disclose or require that the NK cells express an exogenous CD16 protein.
Regarding claim 45, Dipierro does not disclose or require that the NK cells are not genetically engineered.
Regarding claim 47, Dipierro discloses “in some embodiments, the isolated cells are cultured to achieve a therapeutically effective amount of the NK cells or subset thereof. In some embodiments, the isolated cells are cultured to achieve a number of enriched NK cells or subset thereof from or from about 105 to about 1012 cells, from or from about 105 to about 108 cells, from or from about 106 to about 1012 cells, from or from about 108 to about 1011 cells, or from or from about 109 to about 1010 cells” (see 0018).
Dipierro does not specifically teach wherein the NK cells are expanded umbilical cord blood natural killer cells.
Boissel’s general disclosure is to expansion of cord blood natural killer cells using umbilical cord mesenchymal stem cells.
Boissel teaches cord blood NK cell progenitors can be expanded to obtain large numbers by using an irradiated feeder of UC-MSC. They maintain an elevated cytotoxic profile, and may be genetically manipulated—all characteristics that make them suitable for cellular therapies (see abstract).
Therefore it would have been obvious to persons having ordinary skill in the art and before the effective filing date to use natural killer cells which can be expanded from umbilical cord natural killer cells because as Boissel teaches, cord blood NK cell progenitors can be expanded to obtain large numbers by using an irradiated feeder of UC-MSC. They maintain an elevated cytotoxic profile, and may be genetically manipulated—all characteristics that make them suitable for cellular therapies.
Dipierro does not specifically teach wherein the patient has experienced disease progression after treatment with autologous stem cell transplant or chimeric antigen receptor T-cell therapy (CAR-T), wherein the patient has relapsed after treatment with an anti-EGFR antibody, or wherein the patient is subjected to lymphodepleting chemotherapy prior to treatment and wherein the lymphodepleting chemotherapy is non-myeloablative chemotherapy; However it would have been obvious to administer the method of treatment taught by Dipierro to patients who experience disease progression after autologous stem cell transplant or chimeric antigen receptor T-cell therapy (CAR-T) and/or chemotherapies, and who have relapsed after antibody treatment because it is another line of treatment that can help attack the cancer especially if the first line(s) of treatment were not 100% effective.
There would have been a reasonable expectation of success in arriving at the instant invention because Dipierro teaches of administering the same NK cells and antibodies to the same patient populations for treatment of the same cancers.
Conclusion
Currently no claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACOB ANDREW BOECKELMAN whose telephone number is (571)272-0043. The examiner can normally be reached Monday-Friday 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anand Desai can be reached at 571-272-0947. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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JACOB A BOECKELMANExaminer, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
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