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 .
Applicants’ reply to the September 18, 2025 Office Action, filed March 18, 2026, is acknowledged. Applicants previously canceled claims 4. 6. 8-1012-13, 15, 17-21, 23, 26-31, 33-38, 41. 43. 45-47, 50-52, 54-56, and 59-78, and now cancel claims 5, 7, and 39-40. Applicants amend claims 1, 24-25, and 53. Claims 1-3, 11, 14, 16, 22, 24-25, 32, 42, 44, 48-49, 53, and 57-58 are pending in this application, and are under examination.
Any objection or rejection of record in the previous Office Action, mailed September 18, 2025, which is not addressed in this action has been withdrawn in light of Applicants’ amendments and/or arguments. This action is FINAL.
Information Disclosure Statement
The Information Disclosure Statements filed October 14, 2025 and March 18, 2026 have been considered.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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 1-3, 11, 14, 16, 22, 24-25, 32, 42, 44, 48-49, 53, and 57-58 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ang et al. (U.S. Patent Application Publication No. 2020/0390815, published December 17, 2020, filed August 18, 2020, and claiming priority to PCT Patent Application No. PCT/US2019/018989 and U.S. Provisional Patent Application No. 62/633,587, filed February 21, 2019 and February 21, 2018, respectively, and cited in the Information Disclosure Statement filed December 30, 2024 as U.S. Patent Application No. 16/970,930) in view of Shah et al. (8(10) PLOS One e76781, 1-9 (2013), and cited in the Information Disclosure Statement filed May 26, 2021) and Kaur et al. (19 Cytotherapy 433-439 (2017)). This rejection is modified as necessitated by Applicants’ amendments.
Regarding claim 1, Ang discloses a method of expanding natural killer (NK) cells by stimulating mononuclear cells from cord blood in the presence of antigen presenting cells (APCs) and IL-2 (paragraphs [0010]-[0011]). Ang discloses re-stimulation of the cells with APCs (paragraph [0012]).
Regarding claim 2, Ang discloses depletion of CD3 positive cells (paragraph [0081]).
Regarding claim 3, Ang discloses that the depletion takes place between the first stimulation and the re-stimulation (paragraphs [0081] and [0109]).
Regarding claim 5, Ang discloses that the cord blood is thawed out in the presence of Ficoll® (paragraph [0109]).
Regarding claim 11, while Ang discloses that in some embodiments IL-2 is replenished, Ang also discloses that nothing is added or removed during the initial stimulation (paragraphs [0010]-[0011).
Regarding claim 16, Ang discloses that the APCs express membrane-bound IL-21 (mbIL-21), IL-21, IL-15, IL-7, IL-18, and or IL-2 (paragraph [0006]).
Regarding claim 22, Ang discloses that the stimulation takes place over 6 – 8 days. (paragraphs [0082]-[0083]).
Regarding claim 24, Ang discloses that the cells are not split during the stimulation (paragraphs [0010]-[0011]).
Regarding claim 25, Ang discloses that the cells are fed twice with IL-2 (paragraph [0011]).
Regarding claim 32, Ang discloses that the method takes less than 15 days to perform (paragraphs [0082]-[0083]).
Regarding claim 42, Ang discloses that the cord blood is frozen cord blood (paragraph [0109]).
Regarding claim 44, Ang discloses that the cord blood is pooled cord blood (paragraph [0013]).
Regarding claim 48, Ang discloses universal antigen presenting cells (uAPCs) (paragraph [0006]).
Regarding claim 49, Ang discloses that the uAPCs express CS1, CD48, membrane bound IL-21, and 41BB ligand (paragraph [0006]).
Regarding claim 53, Ang discloses that the uAPCs do not express HLA class I, II or CD1d (paragraph [0007]). Ang discloses that that the uAPCs express ICAM-1 (CD54) and LFA-3 (CD58) and are leukemia cell-derived uAPCs (paragraph [0007]).
Regarding claim 57, Ang discloses cryopreservation of the expanded NK cells (paragraph [0083]).
Regarding claim 58, Ang discloses a pharmaceutical composition comprising the expanded immune cells and a pharmaceutically acceptable carrier (paragraph [0018]).
Ang fails to disclose or suggest that the method of expanding NK cells is performed in a bioreactor using good manufacturing practice (GMP). Ang fails to disclose or suggest amount of media used in the first stimulation. Ang fails to disclose or suggest that the starting population is thawed in the presence of dextran, human serum albumin, DNAse and magnesium chloride.
Shah discloses ex vivo expansion of NK cells (abstract and Figure 1). Shah discloses that cryopreserved cord blood is used to expand NK cells in the presences of antigen presenting cells and IL-2 (abstract). Shah discloses a first stimulation, depletion of CD3 cells, and a second stimulation (abstract and page 2, column 2, first full paragraph). Shah discloses that the expansion of the NK cells is performed under GMP compliant method (page 2, column 1, second full paragraph). Shah discloses that the expansion is performed in a bioreactor (page 2, column 2, first full paragraph). Shah discloses that the expanded NK cells show significant in vivo activity against multiple myeloma and provide a clinically acceptable strategy for treating and eradicating multiple myeloma (abstract).
Kaur discloses that umbilical cord blood is a source of hematopoietic stem cells, which can be expanded, along with natural killer (NK) cells (abstract). Kaur discloses that the cord blood can by cryopreserved cord blood (abstract and paragraph bridging pages 433 and 434). Kaur discloses thawing the cord blood and contacting the thawed cord blood with dextran, human serum albumin, DNAse, and magnesium chloride (page 434, paragraph bridging columns 1 and 2). Kaur discloses that the magnesium chloride prevents the cells from clumping (page 434, paragraph bridging columns 1 and 2).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use Shah’s GMP-compliant protocol to expand NK cells in a bioreactor in the presence of Kaur’s dextran, HSA, DNAse, and magnesium chloride using the protocol of Ang and Shah because this provides a method of obtaining clinically useful NK cells that can be used to treat multiple myeloma, without the cells clumping, which provides for better expansion of the NK cells. One of ordinary skill in the art would be motivated to perform Ang’s NK expansion method in Shahs’ bioreactor using GMP-compliant protocols and in the presence of Kaur’s dextran, HSA, DNAse, and magnesium chloride, to obtain an in vivo treatment of multiple myeloma.
Further, it would have been obvious to one with ordinary skill in the art to increase the amount of media in the protocol of Ang, Shah, and Kaur to a desired level, such as 3-5 L, because using Shah’s bioreactor allows for a greater amount of NK cells to be expanded, which is desirable in light of the intended use of treating a disease, such as multiple myeloma. It would have been well within the purview of one ordinarily skilled in the art to increase the amount of media used in Shah’s bioreactor in order to obtain the amount of expanded NK cells necessary for treatment of cancers, such as multiple myeloma.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 48-49, 53, and 58 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6-7, 12, 15, 27, 41 of copending Application No. 16/970,930 (reference application) in view of Kaur et al. (19 Cytotherapy 433-439 (2017)). This rejection is modified as necessitated by Applicants’ amendments.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘930 application claims universal antigen presenting cells (uAPCs) that express CS1, CD48, membrane bound IL-21, and 41BB ligand, but do not express HLA class I, II or CD1d, which is the same expression profile as the uAPCs claimed by the instant application. The ‘930 application claims that the uAPCs express ICAM-1 (CD54) and LFA-3 (CD58) and are leukemia cell-derived uAPCs. The ‘930 application claims that, when co-cultured with NK cells, expansion of the NK cells is induced. The ‘930 application claims a method of expanding immune cells, which are NK cells, by culturing the NK cells in the presence of the uAPCs. The ‘930 application further claims that the NK cells are also cultured in the presence of IL-2. The ‘930 application claims that the NK cells are mononuclear cells. The ‘930 application claims a pharmaceutical composition comprising the expanded immune cells and a pharmaceutically acceptable carrier. The instant application claims a method of inducing expansion of NK cells by co-culturing with uAPCs, the uAPCs of the instant application are the same as those claimed in the ‘930 application. The instant application claims that the expanded NK cells express, or do not express, the same molecules as those claimed by the ‘930 application.
The ’930 application does not claim that the cord blood is thawed in the presence of dextran, human serum albumin, DNAse, and magnesium chloride.
Kaur discloses that umbilical cord blood is a source of hematopoietic stem cells, which can be expanded, along with natural killer (NK) cells (abstract). Kaur discloses that the cord blood can by cryopreserved cord blood (abstract and paragraph bridging pages 433 and 434). Kaur discloses thawing the cord blood and contacting the thawed cord blood with dextran, human serum albumin, DNAse, and magnesium chloride (page 434, paragraph bridging columns 1 and 2). Kaur discloses that the magnesium chloride prevents the cells from clumping (page 434, paragraph bridging columns 1 and 2).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to thaw the ‘930 application’s cord blood in the presence of Kaur’s dextran, human serum albumin, DNAse, and magnesium chloride because this combination of media components provides for the cells to be treated such that there is no cell clumping and can then be expanded, resulting in the required natural killer (NK) cell composition.
Because the uAPCs and method of expanding NK cells have the same expression profiles and method steps, the claims are not deemed to be patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Amendments and Arguments
Regarding the rejection under 35 U.S.C. § 103, Applicants’ arguments have been fully considered, but are not deemed to be persuasive.
Applicants assert that the cited prior art fails to disclose or suggest that the cord blood is thawed in the presence of dextran, human serum albumin, DNAse, and magnesium chloride. Applicants assert that this specific combination of media components is not obvious over the cited prior art.
However, newly cited Kaur discloses that the cord blood is thawed in the presence of dextran, human serum albumin, DNAse, and magnesium chloride. Further, Kaur discloses that the magnesium chloride provides for preventing the cells from clumping.
Because the present combination of cited prior art discloses and suggests each limitation of the claims, this rejection is maintained, as modified in light of Applicants’ amendments.
Regarding the non-statutory double patenting rejection over U.S. Patent Application No. 16/970,930, Applicants state that this rejection will be addressed if it no longer is a provisional rejection. This rejection has also been modified as necessitated by Applicants’ amendments.
Regarding the non-statutory double patenting rejection over U.S. Patent No. 12,473,336 (U.S. Patent Application No. 16/970,937), Applicants’ arguments have been fully considered and are deemed to be persuasive. Because the ‘336 patent’s claims have different steps and require the use of different components than the instant application, the claims are not deemed to be overlapping or obvious variants. Therefore, this rejection is withdrawn.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Each of U.S. Patent Application Publication Nos. 2020/0390816 (U.S. Patent Application No. 16/970,937); 2021/0230548 (U.S. Patent Application No: 17/050,775); 2022/0118013 (U.S. Patent Application No. 17/304,585); and 2022/0265718 (U.S. Patent Application No. 17/661,057) are assigned to the Board of Regents, The University of Texas System, have overlapping inventive entities, and are deemed to have cumulative disclosures, as compared with U.S. Patent Application Publication No. 2020/0390815, which is cited above. Each of the ‘816, ‘548, ‘013, and ‘718 publications are cited in the Information Disclosure Statements filed July 19, 2023 and/or December 30, 2024 (by application number).
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 NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636
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