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 .
Status of the Claims
Applicant’s submission filed 29 June 2026 has been entered. Claims 1, 3-4, 6-9, and 13-17 are pending. Claims 1, 8, 14, and 16 have been amended, while claims 11-12 have been cancelled without prejudice or disclaimer and claim 17 has been newly added. Therefore, prosecution on the merits continues for claims 1, 3-4, 6-9, and 13-17. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Objection to claims 1 and 14
Applicant’s amendments to each of instant claims 1 and 14 correct the minor informalities and thus obviate the objections of record.
Therefore, the objections are withdrawn.
RE: Rejection of claims 1, 3-4, 6-9, and 11-16 under 35 USC 112(a)
The cancellation of claims 11-12 renders the rejection moot for those claims. For the remaining claims, Applicant’s amendments to independent claim 1 removing the limitation requiring the evaluation test to be performed on the formulation at the same time as the step wherein the formulation of immune cells is being stocked obviate the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claim 16 under 35 USC 112(b)
Applicant’s amendments to instant claim 16 correct the antecedent basis of the claim and thus obviate the rejection of record.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1, 4, 6-9, 13, and 16 under 35 USC 102(a)(1) and 35 USC 102(a)(2) over Terunuma et al as evidenced by Gebo et al and Tonog et al
Applicant’s amendments to independent claim 1 requiring the limitations from previous claims 11-12 – which include the selection of a formulation based on KIR ligand mismatch – obviate the rejection of record, as claims 11-12 were not included within the rejection.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1, 4, 6-9, 13-14, and 16 under 35 USC 103 over Terunuma et al as evidenced by Gebo et al and Tonog et al, and in view of Food and Drug Administration
Applicant’s amendments to independent claim 1 requiring the limitations from previous claims 11-12 – which include the selection of a formulation based on KIR ligand mismatch – obviate the rejection of record, as claims 11-12 were not included within the rejection.
Therefore, the rejection is withdrawn.
It is of note that Applicant has not provided any specific arguments against the FDA reference.
RE: Rejection of claims 1, 3-4, 6-9, and 13-16 under 35 USC 103 over Terunuma et al as evidenced by Gebo et al and Tonog et al, and in view of Food and Drug Administration and Yoshikawa et al
Applicant’s amendments to independent claim 1 requiring the limitations from previous claims
11-12 – which include the selection of a formulation based on KIR ligand mismatch – obviate the
rejection of record, as claims 11-12 were not included within the rejection.
Therefore, the rejection is withdrawn.
It is of note that Applicant has not provided any specific arguments against the FDA reference or Yoshikawa et al.
RE: Rejection of claims 1, 4, 6-9, 11-14, and 16 under 35 USC 103 over Terunuma et al as evidenced by Gebo et al and Tonog et al, and in view of Food and Drug Administration and Koehl et al
Applicant's arguments filed 29 June 2026 have been fully considered but they are not persuasive.
Applicant has traversed the rejection, asserting in Pages 6-7 of the Remarks filed 29 June 2026 that the primary reference of Terunuma et al does not relate to an immune cell bank and therefore does not appear to disclose or suggest any criteria for selecting an appropriate formulation from a plurality of banked formulations for a particular recipient, nor does it provide any motivation for considering such selection criteria. In response, the Examiner respectfully submits that the features upon which Applicant relies (i.e., the generation of a cell bank) are not recited in the rejected claims. 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). Instead, the instant claims are directed to a method for providing natural killer cells obtained from a non-recipient donor to a recipient. With that, Terunuma et al disclose that the starting material of natural killer cells is preferably collected from a donor having a human leukocyte antigen (HLA) genotype compatible with that of a recipient. See, for example, Paragraph [0065] of Terunuma et al. Accordingly, the ordinary artisan would have been motivated to select cell formulations based on immune type information of the donor.
Therefore, the rejection is maintained.
RE: Rejection of claims 1, 3-4, 6-9, and 11-16 over claims 5 and 7 of US Patent No. 11,723,924 B2 in view of Terunuma et al as evidenced by Gebo et al and Tonog et al, and further in view of Yoshikawa et al and Koehl et al
Applicant’s amendment to independent claim 1 requiring, in part, the selection of a formulation based on KIR ligand mismatch provides sufficient distinction between the patent claims and instant claims.
Therefore, the rejection is withdrawn.
RE: Rejection of claims 1, 3-4, 6-9, and 11-16 over claims 1 and 5 of US Patent No. 12,329,817 B2 in view of Terunuma et al as evidenced by Gebo et al and Tonog et al, and further in view of Yoshikawa et al and Koehl et al
Applicant’s amendment to independent claim 1 requiring, in part, the selection of a formulation based on KIR ligand mismatch provides sufficient distinction between the patent claims and instant claims.
Therefore, the rejection is withdrawn.
New/Maintained Grounds of Rejection
Claim Objections
Claims 1, 4, and 17 are objected to because of the following informalities:
Regarding claim 1: The instant claim is objected to for reciting “selecting, on KIR ligand mismatch, a formulation” instead of “selecting, based on KIR ligand mismatch, a formulation”, or the like.
Appropriate correction is required.
Regarding claim 4: The instant claim is objected to for reciting “1.0 x 107 to 1.0 x 1010 cells” instead of “1.0 x 107 to 1.0 x 1010 cells”.
Appropriate correction is required.
Regarding claim 17: The instant claim is objected to for reciting “KIR-ligand” while parent claim 1 recites it as “KIR ligand”. Therefore, Applicant must select a consistent term to utilize throughout the claim language.
Appropriate correction is required.
Claim Interpretation
Independent claim 1 is directed to a method for isolating natural killer (NK) cells from a donor:
A method for providing NK cells obtained from a non-recipient donor to a recipient,
which comprises the following steps:
proliferating and/or activating immune cells collected from a donor;
preparing a formulation of the immune cells collected from the donor in a unit suitable for administration;
performing an evaluation test on the formulation, wherein the evaluation test includes a sterility test;
documenting or digitizing immune type information of the donor, wherein the immune type information includes KIR typing;
refrigerating or freezing the formulation, wherein the formulation of the immune cells is stocked with the documented or digitized immune type information of the donor;
and subsequent to the sterility test,
selecting, based on KIR ligand mismatch, a formulation for the recipient from stocked formulations for which the sterility test has been completed.
The claim requires refrigerating or freezing the formulation comprising the immune cells, wherein the formulation of the immune cells is stocked with the “documented or digitized immune type information”, wherein the “immune type information” includes KIR typing.
Thus, the broadest reasonable interpretation of the immune type information of the claimed formulation encompasses a label (i.e. printed matter) with written KIR typing information. However, printed matter is only given patentable weight if a functional relationship exists between the printed matter and the associated substrate, and if the functional relationship between the printed matter and associated substrate must be new and non-obvious (MPEP § 211.05). In the instant case, the printed matter of immune type information – including KIR type – stocked with the formulation comprising immune cells does not modify the formulation. Thus, no functional relationship between the label and the formulation exists, and the method step of “documenting or digitizing immune type information of the donor, wherein the immune type information includes KIR typing” is not given patentable weight.
To the extent Applicant argues a functional relationship of the printed material associated with the formulation exists, labeling formulations with immune cells is not new. See, for example, the Food and Drug Administration reference (HPC Labelling, 2016), which discloses blood fractions comprising cells in biobanks are stored in vials which are labeled (Pages 1, 3-4, 10).
With that, it is of note that changes in the sequence of adding ingredients is prima facie obvious. See MPEP § 2144.04(IV)(C).
Instant claims 1 and 6 utilize the term “includes”. It is of note that the transitional term “includes” is synonymous with "comprises", which is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See MPEP § 2111.03(I).
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.
Claims 1, 3-4, 6-9, and 13-17 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.
Regarding claim 1: A broad limitation together with a narrow limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, independent claim 1 recites the broad recitation of “immune cells” within the method steps, while also reciting “natural killer cells” – which is the narrower statement of the limitation – within the preamble. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Instant claims 3-4, 6-9, and 13-17 depend from parent claim 1 and thus inherent the deficiencies of the parent claim.
Appropriate correction is required.
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, 6-9, 13, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Terunuma et al (US 2016/0075996 A1, of record) as evidenced by Gebo et al (J Clin Microbiol, 2020, of record) and Tonog et al (StatPearls, 2022, of record) in view of Koehl et al (Oncoimmnuology, 2015, of record).
Terunuma et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). Koehl et al is considered prior art under 35 USC 102(a)(1).
The following rejection follows the Claim Interpretation above, wherein a functional relationship between the label comprising the KIR type information and the formulation does not exist, and the method step of “documenting or digitizing immune type information of the donor, wherein the immune type information includes KIR typing” is not given patentable weight.
Regarding claims 1, 6, 8, and 17: Terunuma et al disclose methods for producing a natural killer (NK) cell-enriched blood preparation (Abstract).
As such, Terunuma et al disclose a method wherein peripheral blood containing NK cells is collected from a donor, activated with a NK cell growth-stimulating factor that enriches for NK cells, and cultured to increase the number of NK cells (Paragraphs [0064]-[0065], [0074], [0092]-[0093], [0106]). Terunuma et al further disclose that the cultured NK cells are then subject to cytotoxicity assays – wherein the cytotoxic activity of the activated and cultured NK cells is measured by activation marker expression – and then either immediately administered to a patient or stored at a temperature of 0°C to 8°C, or -80°C for later use (Paragraphs [0124]-[0125]). Terunuma et al further disclose that a contamination test must be performed on the NK cells at the end of the culturing step prior to the refrigeration or freezing of the enriched NK cells and subsequent administration to a patient in need thereof (Paragraphs [0106]-[0115], [0125], [0169]-[0172]). It is of note that Terunuma et al further disclose that the patient may be a cancer patient (Paragraphs [0118], [0150], [0159]).
Although Terunuma et al further disclose that the blood is preferably collected from a donor having a human leukocyte antigen (HLA) genotype compatible with that of a recipient (Paragraph [0065]), Terunuma do not explicitly disclose the selection of a final NK cell-enriched blood preparation for a patient based on KIR type information, as required by instant claim 1.
Koehl et al, however, disclose that typing of KIR and HLA are important sample features to consider when selecting an NK cell donor sample for administration to a recipient (Pages 3-4, 7). Koehl et al further disclose that selecting an NK cell donor sample for administration to a recipient is based on KIR mismatch (Pages 3-4).
Therefore, it would have been prima facie obvious to have modified the method of Terunuma et al such that a NK cell-enriched blood preparation is selected to administer to a patient based on KIR typing information in addition to the HLA typing information, as detailed in Koehl et al. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to utilize the KIR typing information for formulation selection, as it is critical for selecting an auspicious NK cell donor (Koehl et al: Page 7), and would have had a reasonable expectation of success based on the detailed protocols and consideration of the immune type information and sterility of the samples already outlined in Terunuma et al (Paragraphs [0064]-[0065], [0074], [0092]-[0093], [0106]-[0115], [0124]-[0125], [0169]-[0172]) coupled with the KIR typing protocols outlined in Koehl et al (Pages 3-4). See MPEP § 2143(I)(G) and 2144.04(IV)(C).
Consequently, Terunuma et al as modified by Koehl et al render obvious a method of generating an NK cell-enriched blood preparation, wherein peripheral blood containing NK cells is collected from a donor; activated with a NK cell growth-stimulating factor and cultured to increase the number of NK cells; assessed for activation marker expression and cytotoxic activity (claim 6); evaluated for any contamination within the NK cells via a contamination test; stored at a temperature of 0°C to 8°C, or -80°C; and then selected for an HLA-matched and KIR-mismatched (claim 17) cancer patient (claim 8). As a contamination test is synonymous with a sterility test (see Gebo et al: Page 2, Paragraph 2; Figure 1), this therefore renders obvious the method of instant claim 1.
It is of note that Gebo et al is cited solely as evidence to show that the contamination test of Terunuma et al is inherently a sterility test as claimed. See MPEP § 2112.
Regarding claim 4: Following the discussion of claim 1, Terunuma et al further disclose that one dose – or unit – of the NK cell-enriched blood preparation can be a volume containing NK cells in the range of 20 x 107 to 5x109 cells (Paragraph [0154]). As this dosage lies within the claimed range, this therefore reads on the method of the instant claim. See MPEP § 2131.03.
Regarding claim 7: Following the discussion of claim 1, Terunuma et al further disclose that NK cell-enriched blood preparation can be diluted with normal saline and administered to a patient via an intravenous drip (Paragraphs [0123], [0153]). As normal saline is inherently an isotonic solution (see Tonog et al: Page 2, 0.9% Sodium Chloride (Normal Saline), this therefore reads on the method of the instant claim.
It is of note that Tonog et al is cited solely as evidence to show that the normal saline of Terunuma et al is inherently an isotonic solution as claimed. See MPEP § 2112. Furthermore, although the publication date of Tonog et al is 2022, MPEP §2124 establishes references which show inherency need not antedate the filing date.
Regarding claim 9: Following the discussion of claim 1, Terunuma et al disclose that the donor is a healthy human (Paragraph [0177]). This therefore reads on the method of the instant claim.
Regarding claim 13: Following the discussion of claim 1, Terunuma et al further disclose that, since the enriched NK cells are activated prior to being stored, the stored NK cells can be administered in a necessary amount to a subject at the time of need via injection (Paragraphs [0127]-[0128], [0153]). As Terunuma et al is silent to the re-expansion and/or re-activation of the stored NK cells upon administration, this therefore reads on the method of the instant claim.
Regarding claim 16: Following the discussion of claim 1, Terunuma et al further disclose that the NK cell growth-stimulating factors that enrich for NK cells are an anti-CD16 antibody, an anti-CD137 antibody, OK432, and cytokines (Paragraphs [0075]-[0081], [0108]). This therefore reads on the method of the instant claim.
Claims 1, 4, 6-9, 13-14, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Terunuma et al (US 2016/0075996 A1, of record) as evidenced by Gebo et al (J Clin Microbiol, 2020, of record) and Tonog et al (StatPearls, 2022, of record) in view of Food and Drug Administration (HPC Labelling, 2016) and Koehl et al (Oncoimmnuology, 2015, of record).
Terunuma et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2). The Food and Drug Administration (FDA) reference is considered prior art under 35 USC 102(a)(1). Koehl et al is considered prior art under 35 USC 102(a)(1).
The following rejection follows the Claim Interpretation above, wherein Applicant argues that a functional relationship between the label comprising the KIR type information and the formulation does exist, and the method step of “documenting or digitizing immune type information of the donor, wherein the immune type information includes KIR typing” is given patentable weight.
Regarding claims 1, 6, 8, and 17: Terunuma et al disclose methods for producing a natural killer (NK) cell-enriched blood preparation (Abstract).
As such, Terunuma et al disclose a method wherein peripheral blood containing NK cells is collected from a donor, activated with a NK cell growth-stimulating factor that enriches for NK cells, and cultured to increase the number of NK cells (Paragraphs [0064]-[0065], [0074], [0092]-[0093], [0106]). Terunuma et al further disclose that the cultured NK cells are then subject to cytotoxicity assays – wherein the cytotoxic activity of the activated and cultured NK cells is measured by activation marker expression – and then either immediately administered to a patient or stored at a temperature of 0°C to 8°C, or -80°C for later use (Paragraphs [0124]-[0125]). Terunuma et al further disclose that a contamination test must be performed on the NK cells at the end of the culturing step prior to the refrigeration or freezing of the enriched NK cells and subsequent administration to a patient in need thereof (Paragraphs [0106]-[0115], [0125], [0169]-[0172]). It is of note that Terunuma et al further disclose that the patient may be a cancer patient (Paragraphs [0118], [0150], [0159]).
Although Terunuma et al further disclose that the blood is preferably collected from a donor having a human leukocyte antigen (HLA) genotype compatible with that of a recipient (Paragraph [0065]), Terunuma do not explicitly disclose stocking the NK cell-enriched blood preparation with KIR type information, nor the selection of a final NK cell-enriched blood preparation for a patient based on that KIR type information, as required by instant claim 1.
The FDA reference, however, discloses procedures for the procurement, storage, and use of blood and the cells comprised within (Page 1). As such, the FDA reference discloses the labeling of the obtained blood samples with pertinent information, including the HLA type of the sample (Pages 3, 10). The FDA reference further discloses that quality control tests must be performed and documented on the samples, including the results of sterility testing (Pages 6, 18-19).
With that, Koehl et al disclose that typing of KIR and HLA are important sample features to consider when selecting an NK cell donor sample for administration to a recipient (Pages 3-4, 7). Koehl et al further disclose that selecting an NK cell donor sample for administration to a recipient is based on KIR mismatch (Pages 3-4).
Therefore, it would have been prima facie obvious to have modified the method of Terunuma et al to label the NK cell-enriched blood preparation with the donor HLA and KIR type information and sterility testing results, and then select a NK cell-enriched blood preparation to administer to a patient that is appropriately HLA-matched and KIR-mismatched to the receiving patient, as is detailed in the FDA reference and Koehl et al. One of ordinary skill before the effective filing date of the invention would have been motivated to ensure that the immune type information – particularly the HLA and KIR type – of the donor and recipient are appropriately recorded and taken into account, as administering a NK cell-enriched blood preparation that is HLA-matched and KIR-mismatched reduces the possibility of an adverse immune reaction within the recipient (Terunuma et al: Paragraphs [0065], [0155]; Koehl et al: Page 7). The ordinary artisan also would have been motivated to ensure that the obtained blood sample is sterile – or contamination-free – and appropriately labelled on the sample along with the immunotype information, as contaminated blood samples cannot be utilized for downstream therapies (FDA reference: Page 6). Furthermore, the ordinary artisan would have had a reasonable expectation of success based on the detailed protocols and consideration of the immune type information and sterility of the samples already outlined in Terunuma et al (Paragraphs [0064]-[0065], [0074], [0092]-[0093], [0106]-[0115], [0124]-[0125], [0169]-[0172]) coupled with the labeling protocols outlined in the FDA reference (Pages 3, 6, 10, 18-19) and KIR typing protocols outlined in Koehl et al (Pages 3-4). See MPEP § 2143(I)(G) and 2144.04(IV)(C).
Consequently, Terunuma et al as modified by the FDA reference and Koehl et al render obvious a method of generating an NK cell-enriched blood preparation, wherein peripheral blood containing NK cells is collected from a donor; activated with a NK cell growth-stimulating factor and cultured to increase the number of NK cells; assessed for activation marker expression and cytotoxic activity (claim 6); labelled with the donor HLA and KIR type information, evaluated for any contamination within the NK cells via a contamination test, and stored at a temperature of 0°C to 8°C, or -80°C; and then selected for an HLA-matched and KIR-mismatched (claim 17) cancer patient (claim 8). As a contamination test is synonymous with a sterility test (see Gebo et al: Page 2, Paragraph 2; Figure 1), this therefore renders obvious the method of instant claim 1.
It is of note that Gebo et al is cited solely as evidence to show that the contamination test of Terunuma et al is inherently a sterility test as claimed. See MPEP § 2112.
Regarding claim 4: Following the discussion of claim 1, Terunuma et al further disclose that one dose – or unit – of the NK cell-enriched blood preparation can be a volume containing NK cells in the range of 20 x 107 to 5x109 cells (Paragraph [0154]). As this dosage lies within the claimed range, this therefore reads on the method of the instant claim. See MPEP § 2131.03.
Regarding claim 7: Following the discussion of claim 1, Terunuma et al further disclose that NK cell-enriched blood preparation can be diluted with normal saline and administered to a patient via an intravenous drip (Paragraphs [0123], [0153]). As normal saline is inherently an isotonic solution (see Tonog et al: Page 2, 0.9% Sodium Chloride (Normal Saline), this therefore reads on the method of the instant claim.
It is of note that Tonog et al is cited solely as evidence to show that the normal saline of Terunuma et al is inherently an isotonic solution as claimed. See MPEP § 2112. Furthermore, although the publication date of Tonog et al is 2022, MPEP §2124 establishes references which show inherency need not antedate the filing date.
Regarding claim 9: Following the discussion of claim 1, Terunuma et al disclose that the donor is a healthy human (Paragraph [0177]). This therefore reads on the method of the instant claim.
Regarding claim 13: Following the discussion of claim 1, Terunuma et al further disclose that, since the enriched NK cells are activated prior to being stored, the stored NK cells can be administered in a necessary amount to a subject at the time of need via injection (Paragraphs [0127]-[0128], [0153]). As Terunuma et al is silent to the re-expansion and/or re-activation of the stored NK cells upon administration, this therefore reads on the method of the instant claim.
Regarding claim 14: Following the discussion of claim 8, the FDA reference discloses that HLA matching of donor samples to recipient is recommended, as it helps prevent graft failure and leads to a faster recovery of the cells within the recipient (Pages 2-3, 5, 11).
With that, as aforementioned, Koehl et al disclose that selecting an NK cell donor sample for administration to a recipient is based on KIR mismatch (Pages 3-4).
Therefore, it would have been prima facie obvious to have modified the method of Terunuma et al such that NK cell-enriched blood preparations from multiple donors having a variety of HLA and KIR types are formulated and stored. One of ordinary skill in the art before the effective filing date of the invention would have been motivated to comprise a wide array of HLA and KIR types, as it is recommended that at least 4 of 6 HLA-A antigens, HLA-B antigens, and HLA-DRB1 alleles match between donor and recipient (FDA reference: Page 3) and there is a greater than 10-fold difference in KIR type (Koehl et al: Page 3), and would have had a reasonable expectation of success given that the disclosure of Terunuma et al is concerned with the immunotyping of the collected samples (Paragraph [0065]). See MPEP § 2143(I)(G).
Consequently, Terunuma et al as modified by the FDA reference and Koehl et al render obvious a method of generating an NK cell-enriched blood preparation, wherein NK cell-enriched blood preparations having a variety of HLA and KIR types are maintained and stored. This therefore renders obvious the method of the instant claim.
Regarding claim 16: Following the discussion of claim 1, Terunuma et al further disclose that the NK cell growth-stimulating factors that enrich for NK cells are an anti-CD16 antibody, an anti-CD137 antibody, OK432, and cytokines (Paragraphs [0075]-[0081], [0108]). This therefore reads on the method of the instant claim.
Claims 1, 3-4, 6-9, and 13-17 are rejected under 35 U.S.C. 103 as being unpatentable over Terunuma et al (US 2016/0075996 A1, of record) as evidenced by Gebo et al (J Clin Microbiol, 2020, of record) and Tonog et al (StatPearls, 2022, of record) in view of Food and Drug Administration (HPC Labelling, 2016) and Koehl et al (Oncoimmnuology, 2015, of record), and further in view of Yoshikawa et al (US 2014/0087465 A1, of record).
The discussion of Terunuma et al as evidenced by Gebo et al in view of the FDA reference and Koehl et al regarding claim 1 can be observed above and is relied upon herein, the content of which is incorporated in its entirety. Terunuma et al as evidenced by Gebo et al and Tonog et al in view of the FDA reference and Koehl et al render obvious claims 1, 4, 6-9, 13-14, and 16-17. Yoshikawa et al is considered prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Regarding claim 3: Following the discussion of claim 1 above, Terunuma et al further disclose that the NK cells are collected within peripheral blood in a blood collection bags (Paragraph [0069]).
The combination of Terunuma et al, the FDA reference, and Koehl et al fail to teach that the blood collection bags are resin bags, as required by instant claim 3.
Yoshikawa et al, however, disclose the culture of adherent cells within polyolefin resin bags (Abstract; Paragraphs [0003], [0017]-[0018], [0027]-[0034], [0046]-[0049]).
Therefore, it would have been prima facie obvious to have substituted the blood collection bag of Terunuma et al with the cell culture bag of Yoshikawa et al, as doing so would have been a simple substitution of one culture bag for another. See MPEP § 2143(I)(B). One of ordinary skill before the effective filing date of the invention would have recognized that the two culture bags are functionally comparable, as they both allow for the culture of adherent cells comprised within the bag, and thereby would have been able to substitute the culture bags with predictable results.
Consequently, Terunuma et al as modified by the FDA reference, Koehl et al, and Yoshikawa et al render obvious a method of generating an NK cell-enriched blood preparation, wherein the NK cells are held within a culture bag constructed from polyolefin resin. This therefore renders obvious the method of the instant claim.
Regarding claim 15: Following the discussion of claim 1 above, Terunuma et al further disclose that the NK cells are collected within peripheral blood in a blood collection bags (Paragraph [0069]).
The combination of Terunuma et al, the FDA reference, and Koehl et al fail to teach that the blood collection bags are inverted during the proliferation and/or activation of the NK cells within the blood sample, as required by instant claim 15.
Yoshikawa et al, however, disclose the culture of adherent cells within polyolefin resin bags, wherein the cells adhere to at least one inner surface of the culture bag during expansion by reversing – or inverting – the culture bag (Abstract; Paragraphs [0003], [0012]-[0013], [0017]-[0019], [0027]-[0034], [0039], [0046]-[0049]).
Therefore, it would have been prima facie obvious to have modified the method of Terunuma et al in view of the FDA reference and Koehl et al such that the collection bags are inverted during the proliferation and/or activation of the NK cells within the blood sample, as detailed in Yoshikawa et al. One of ordinary skill before the effective filing date of the invention would have been motivated to ensure that the NK cells are expanding to their full potential by adhering and proliferating upon both sides of the collection bag (Yoshikawa et al: Paragraph [0049]), and would have had a reasonable expectation of success given that the disclosures of Terunuma et al and Yoshikawa et al are both concerned with the culture and expansion of cells within culture bags. See MPEP § 2143(I)(G).
Consequently, Terunuma et al as modified by the FDA reference, Koehl et al, and Yoshikawa et al render obvious a method of generating an NK cell-enriched blood preparation, wherein the collection bags housing the NK cells are inverted during the proliferation and/or activation of the NK cells within the blood sample. This therefore renders obvious the method of the instant claim.
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 ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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, Christopher Babic can be reached at (571) 272-8507. 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.
/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
Prosecution Insights