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 .
Detailed Action
Claims 33-41 are new.
Claims 2, 4, 9, 11-12, 17-21, and 29 are cancelled.
Claims 1, 22, 27, and 30 are amended.
Claims 1, 3, 5-8, 10, 13-16, 22-28, and 30-41 are pending and under examination on the merits.
Priority
This application is a 371 of PCT/US2018/63362, which claims benefit of U.S. Provisional Application Serial No. 62/596,659, filed December 8, 2017 and U.S. Provisional Application Serial No. 62/657,626, filed April 13, 2018.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after appeal to the Patent Trial and Appeal Board, but prior to a decision on the appeal. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 02/17/2026 has been entered.
Information Disclosure Statement
The IDS submission filed on 02/17/2026 has been considered by the Examiner.
New Rejections
New-Claim Interpretation
The recited variant thereof/variant of CD16 is understood to be sufficiently described via a representative number of species provided by the variants described in the instant Application (see for example paragraphs 000113 and 000138 as well as W02015148926A2, cited and incorporated by reference at paragraph 000139 of the instant specification).
The recitation of “the iPSC” in part (i) of claim 38 is interpreted to refer to (and derive antecedent basis from) the iPSC of claim 1.
In the interest of advancing prosecution, adding a therapeutic agent of part (ii) of claim 38 to the cell of part (i) of claim 38 is being interpreted as required for the method of preparing a composition recited by claim 38.
New-Claim Objections
Claims 3, 6-7, 10, 13-15, 22-25, 27-28 and 33-37 are objected to for their dependency from rejected base claims, but would be allowable if rewritten in independent form.
New-Claim Rejections - 35 USC § 112
35 USC § 112(b)
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 38-41 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.
It is unclear whether part (ii) of claim 38 (the recitation that the composition comprises the derivative cell and one or more therapeutic agents) is required limitation or if part (ii) is merely optional. Part (ii) is notably not recited as an active step of a result of practicing a method step, and claim 38, from the preamble, appears to be intentionally directed towards a method of preparing a composition. Artisans are left to dispute whether part (ii) is required in order to infringe the claim as drafted.
Claims 39-41 are included in this rejection because they incorporate, via dependency, this ambiguity and do not clarify the claimed scope.
Claim 39 is further rejected because it is unclear what ‘one or more polynucleic acids of interest’ is intended to encompass. Paragraph 000113 at page 29 of the instant specification provides that “a polynucleotide sequence of interest” may be “ a DNA sequence that is transcribed into RNA and in some instances translated into a polypeptide in vivo when placed under the control of appropriate regulatory sequences. A gene or polynucleotide of interest can include, but is not limited to, prokaryotic sequences, cDNA from eukaryotic mRNA, genomic DNA sequences from eukaryotic (e.g., mammalian) DNA, and synthetic DNA sequences”. However, no further definition is provided. Artisans are left to dispute the scope of a protected polynucleotide of interest. A polynucleotide may be viewed to be ‘of interest’ by one artisan, but may be deemed to be excluded from the claim scope by another artisan. Therefore, the metes and bounds of the claim are indefinite.
New-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.
The enumerated claims are rejected on the ground of nonstatutory double patenting as being unpatentable over enumerated claims of the enumerated reference US Patents, as follows:
Claims 1, 8, and 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12203098 B2 (reference A);
claims 1, 8, and 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 12435123 B2 (reference B); and
claims 1, 8, and 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12173274 B2 (reference C);
and
The enumerated claims are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the enumerated claims of the enumerated reference copending applications, as follows:
claims 1, 8, and 30-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6-15, 18-28, and 33-34 of copending Application No. 18/917,836 (‘836);
claims 1, 5, 8, 22, and 30-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 22-23, 29-31, 60, 66, and 87 of copending Application No. 18/854,914 (‘914);
claims 1, 5, 8, and 30-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10-11, 16, 22-23, 34, 38, 42, 43-46, 49, 59, 61, 77-80, 85, and 90-91 of copending Application No. 18/854,296 (‘296);
claims 1, 8, and 30-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 8, 12, 14, 16-19, 22-23, 25, 29-45, and 68-70 of copending Application No. 18/706,961 (‘961);
claims 1, 8, and 30-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11, 13-19, and 67-83 of copending Application No. 18/250,735 (‘735);
claims 1, 8, and 30-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-42 of copending Application No. 18/028,457 (‘457); and
claims 1, 8, and 30-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-42 of copending Application No. 17/782,600 (‘600).
The claims are not verbatim but the recitations of the reference claims encompass embodiments which read directly upon the instant claims as enumerated in the rejections. Note that efforts were made to discover any pending applications or granted US patents that claimed patentably indistinct subject matter. However, it is also noted that the number of patent applications filed on this or related subject matter is significant. Applicant is in the best position to identify any other pending applications of US Patents that are directed to the instantly claimed cell or population thereof and methods of making/manufacturing/using said cell or population thereof as well as compositions of other products encompassing said cell or population thereof. Assistance in identifying such documents is appreciated.
Reference A: Regarding claims 1, 8, and 30-32, reference A claims a cell or a population thereof, wherein the cell is (a) an immune cell; (b) an induced pluripotent cell (iPSC); or (c) a derivative effector cell obtained from differentiating the iPSC. Dependent claim 12 adds that the cell further comprises a polynucleotide encoding an exogenous CD16 or a variant thereof and a polynucleotide encoding a cytokine signaling complex comprising a partial or full peptide of a cell surface expressed exogenous cytokine and/or a receptor thereof. Dependent claim 22 adds that the cytokine signaling complex comprises at least one of, for example, a fusion protein of IL15 and IL15Rα or an IL15/IL15Rα fusion protein with intracellular domain of IL15Rα truncated.
Claims 1, 12, and 22 of reference A anticipate the cell of instant claims 1, 8, and 30-32.
Reference B: Regarding instant claims 1, 8, and 30-32, reference B’s claim 1 recites a cell of population thereof where the cell may be an induced pluripotent cell (iPSC) or a derivative cell obtained from differentiating the iPSC. Dependent claim 3 of reference B adds that the cell further comprises one or more of, for example, an exogenous CD16 or a variant thereof. Dependent claim 9 of reference B adds that the cell further comprises, for example, a fusion protein of IL15 and membrane bound sushi domain of IL15Rα or an IL15/IL15Rα fusion protein with intracellular domain of IL15Rα truncated. Recitations that the cell or population comprises a protein or expression thereof (for example an exogenous CD16 or a variant thereof) are understood to mean that the cell has one or more polynucleotides encoding said protein (such as the CD16 or variant thereof).
Claims 1, 3, and 9 of reference B anticipate the cell of instant claims 1, 8, and 30-32.
Reference C: Regarding instant claims 1, 8, and 30-32 reference C’s claim 1 recites a cell or population thereof wherein the cell is an induced pluripotent stem cell (iPSC), a clonal iPSC, or an iPSC cell line cell. Dependent claim 3 of reference C adds that the cell comprises an exogenous CD16 or a variant thereof. Dependent claim 13 of reference C adds that the cell comprises one or more fusions, including a partial or full peptide of IL15 fused with a partial IL15Rα, wherein the IL15Rα has its intracellular domain truncated. Recitations that the cell or population comprises a protein or expression thereof (for example an exogenous CD16 or a variant thereof) are understood to mean that the cell has one or more polynucleotides encoding said protein (such as the CD16 or variant thereof).
Claims 1, 3, and 13 of reference C anticipate the cell of instant claims 1, 8, and 30-32.
Copending ‘836: Regarding claims 1, 8, and 30-32, ‘836’s claim 1 recites a cell or population thereof wherein the cell is an induced pluripotent cell (iPSC), a clonal iPSC, or an iPS cell line cell, or a derivative cell obtained from differentiating the iPSC, wherein the cell may have an exogenous polynucleotide encoding a CD16 or a variant thereof one or more of an exogenous polynucleotide encoding a cytokine signaling complex comprising a partial or full peptide of a cell surface expressed exogenous cytokine and/or a receptor thereof. Dependent claim 14 of ‘836 adds that the cytokine signaling complex comprises, for example, at least one of a fusion protein of IL15 and IL15Ra and/or an IL15/IL15Ra fusion protein with intracellular domain of IL15Ra truncated.
Claims 1 and 14 of ‘836 anticipate the cell of instant claims 1, 8, and 30-32.
Copending ‘914: Regarding instant claims 1, 8, and 30-32, claim 1 of ‘914 recites a cell or a population thereof, wherein the cell is an induced pluripotent cell (iPSC) or a derivative effector cell obtained from differentiating the iPSC. Dependent claim 3 of ‘914 adds that the cell further comprises a polynucleotide encoding an exogenous CD16 or a variant thereof and a polynucleotide encoding a cytokine signaling complex comprising a partial or full peptide of a cell surface expressed exogenous cytokine and/or a receptor thereof. Dependent claim 13 of ‘914 adds that the cell further comprises the cytokine signaling complex comprising at least one of, for example, a fusion protein of IL15 and IL15Ra and/or an IL15/IL15Ra fusion protein with intracellular domain of IL15Ra truncated.
Claims 1, 3, and 13 of ‘914 anticipate the cell of instant claims 1, 8, and 30-32.
Copending ‘296: Regarding instant claims 1, 5, 8, and 30-32, claim 1 of ‘296 recites a cell or a population thereof, wherein the cell is an induced pluripotent cell (iPSC) or a derivative cell obtained from differentiating the iPSC. Dependent claim 23 of ‘296 adds that the cell further comprises an exogenous polynucleotide encoding CD16 or a variant thereof and an exogenous polynucleotide encoding a partial or full peptide of IL15 and a partial or full peptide of IL15 receptor. Independent claim 77 of ‘296 recites a cell or a population thereof, wherein the cell is an induced pluripotent cell (iPSC) or a derivative effector cell obtained from differentiating the iPSC wherein the iPSC and the derivative effector cell comprise an exogenous polynucleotide encoding an exogenous CD16 or variant thereof and an exogenous polynucleotide encoding a cytokine signaling complex comprising a partial or full peptide of a cell surface expressed exogenous cytokine. Dependent claim 85 of ‘296 recites that the cell or a population thereof of claim 77 of ‘296 is further characterized by one or more of the following characteristics: the cytokine signaling complex comprises, for example, an IL15/IL15Ra fusion protein with intracellular domain of IL15Ra truncated and/or wherein the exogenous CD16 or variant thereof is a high affinity non-cleavable CD16 (hnCD16).
Claims 1, 23, 77, and 85 of ‘914 anticipate the cell of instant claims 1, 5, 8, and 30-32.
Copending ‘961: Regarding claims 1, 8, and 30-32, claim 1 of ‘961 recites a composition comprising a cell or population thereof, wherein the cell may be an induced pluripotent cell (iPSC) or a derivative cell obtained from differentiating the iPSC, wherein the cell comprises a CD16 or a variant thereof (see also, dependent claim 3, part (iv) of ‘961). Dependent claim 18 of ‘961 adds that the cell of claim 3 of ‘961 further comprises the cytokine signaling complex, which comprises at least one of, for example, a fusion protein of IL15 and IL15Ra and/or an IL15/IL15Ra fusion protein with intracellular domain of IL15Ra truncated.
Recitations that the cell or population comprises a protein or expression thereof (for example an exogenous CD16 or a variant thereof) are understood to mean that the cell has one or more polynucleotides encoding said protein (such as the CD16 or variant thereof).
Claims 1, 3, and 18 of ‘961 anticipate the cell of instant claims 1, 8, and 30-32.
Copending ‘735: Regarding claims 1, 8, and 30-32, claim 1 of ‘735 recites a cell or a population thereof wherein the cell is an induced pluripotent cell (iPSC) or a derivative cell differentiated therefrom. Dependent claim 5 of ‘735 adds that the cell or a population thereof of claim 1 of ‘735 further comprises for example, an exogenous CD 16 or a variant thereof. Dependent claim 8 adds that the cell or a population thereof of claim 5 of ‘735 further comprises at least one of, for example, a fusion protein of IL15 and IL15Ra and/or an IL15/IL15Ra fusion protein with intracellular domain of IL15Ra truncated.
Recitations that the cell or population comprises a protein or expression thereof (for example an exogenous CD16 or a variant thereof) are understood to mean that the cell has one or more polynucleotides encoding said protein (such as the CD16 or variant thereof).
Claims 1, 5, and 8 of ‘735 anticipate the cell of instant claims 1, 8, and 30-32.
Copending ‘457: Regarding claims 1, 8, and 30-32, claim 14 of ‘457 recites a cell or a population thereof wherein the cell is an induced pluripotent stem cell (iPSC), a clonal iPSC, or an derivative iPSC-derived effector cell. Dependent claim 15 of ‘457 adds that the cell or population thereof of claim 14 of ‘457 further comprises one or more of, for example, a CD16 or a variant thereof. Dependent claim 19 of ‘457 adds that the cell or population thereof of claim 15 of ‘457 comprises a partial or full peptide of a cell surface expressed exogenous cytokine and/or a receptor thereof, wherein the exogenous cytokine or receptor thereof comprises at least one of, for example, a fusion protein of IL15 and IL15Ra and/or an IL15/IL15Ra fusion protein with intracellular domain of IL15Ra truncated.
Recitations that the cell or population comprises a protein or expression thereof (for example an exogenous CD16 or a variant thereof) are understood to mean that the cell has one or more polynucleotides encoding said protein (such as the CD16 or variant thereof).
Claims 14, 15, and 19 of ‘457 anticipate the cell of instant claims 1, 8, and 30-32.
Copending ‘600: Regarding claims 1, 8, and 30-32, claim 12 of ‘600 recites a cell or a population thereof. Dependent claim 13 of ‘600 adds that the cell or the population thereof of claim 12 of ‘600, wherein the cell may be a derivative effector immune cell differentiated from an induced pluripotent stem cell (iPSC). Dependent claim 14 of ‘600 adds that the cell or the population thereof of claim 13 of ‘600 further comprises at least one or more edit(s) including, for example, a CD16 or a variant thereof. Dependent claim 16 of ‘600 adds that the cell or the population thereof of claim 14 of ‘600 further comprises at least one of, for example, a fusion protein of IL15 and IL15Ra and/or an IL15/IL15Ra fusion protein with intracellular domain of IL15Ra truncated or eliminated.
Recitations that the cell or population thereof comprises a protein or expression thereof (for example an exogenous CD16 or a variant thereof) are understood to mean that the cell has one or more polynucleotides encoding said protein (such as the CD16 or variant thereof).
Claims 12-14 and 16 of ‘600 anticipate the cell of instant claims 1, 8, and 30-32.
The enumerated claims of the enumerated US Patents and US Patent Applications, viewed individually, claim a cell or population thereof (or a composition thereof) which read directly on the instantly recited cell or population thereof. While not verbatim, the reference/copending claims noted in the rejections above encompass the subject matter of the enumerated instant claims in a manner consistent with anticipation.
Claim 16 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 8, 12, 14, 16-19, 22-23, 25, 29-45, and 68-70 of copending Application No. 18/706,961 (‘961), as applied to claims 1, 8, and 30-32 above, in further view of Yao et al (Reprod Med Biol. 2017;16:99–117; DOI: 10.1002/rmb2.12024).
Reference G claims a composition encompassing the claimed cell or population thereof meeting the limitations of instant claim 1 (see for, example, claims 1 and 18 of reference G).
Reference G does not claim the composition comprising a pharmaceutically acceptable medium or carrier.
However, Yao et al teach that medium supports cell survival and proliferation, as well as cellular
functions (see for example, column 2 of page 99 and sections 28.1-2.8.2 at pages 105-108).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosure of references G and Yao et al because Yao et al teach that medium, such as the pharmaceutically acceptable media listed at Table 3 on page 107, support cell survival and the artisan would have presumably desired the cells to survive in the composition, motivating the use of medium as taught by Yao et al for the composition of reference G.
Conclusion
Notice of Allowable Matter
The claims are deemed free from the prior art, thus directed towards allowable subject matter. The closest prior art is the art cited in the previous office action dated 03/19/2025. The prior art cited therein fails to teach or make obvious an iPSC (undifferentiated pluripotent stem cell) having one or more polynucleotides encoding the elements recited in instant claims 1, 26, or 30. Editing of undifferentiated pluripotent stem cells is highly unpredictable. Uenaka et al (Cell Stem Cell. 2026 Mar 5;33(3):517-530.e8. doi: 10.1016/j.stem.2026.01.007. Epub 2026 Feb 13) teach that stable transgene expression remains challenging during human pluripotent stem cell differentiation (see for example, the ‘In brief’ section at page 516). At this point, the mechanisms of transgene silencing during pluripotent cell differentiation are not understood and transgene silencing has also been observed in undifferentiated pluripotent cells without the context of differentiation (see for example, column 1 of page 526). Moy et al-2024 (Med Res Arch. 2023 November ; 11(11): . doi:10.18103/mra.v11i11.4784; available in PMC 2024 January 05) further confirm that while induced pluripotent stem cells (iPSC) represent a potentially exciting regenerative-medicine cell therapy for several chronic conditions, the field of iPSC therapeutics currently exists at an early stage of development and iPSC therapies pose significant unique challenges with respect to safety, potency, genetic stability, immunogenicity, tumorgenicity, cell reproducibility, scalability and engraftment that need to be addressed before iPSC technology can be fully realized as a cell replacement therapy (see for example, the abstract). Therefore, the state of the art, even after the effective filing date of the instant Application, cannot reasonably be deemed to have provided one of ordinary skill in the art with a reasonable expectation of success with inserting/transfecting/editing/knocking-in the recited IL15 construct(s)/options and/or CD16 variant options into an iPSC, clonal iPSC, or an iPS cell line cell. This was considered as strongly limiting any reasonable expectation of success for 103 obviousness and double patenting analysis (see for example, MPEP §2143.02). For this reason, the claims, as presently drafted, are deemed free from the prior art.
Any inquiry concerning this communication or earlier communications from the
examiner should be directed to ASHLEY GAO whose telephone number is (571) 272-5695. The
examiner can normally be reached on M-F 9:00 am - 6:00 pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
supervisor, Gregory Emch can be reached on (571) 272-8149. The fax phone number for the
organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent
Application Information Retrieval (PAIR) system. Status information for published applications,
may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
applications is available through Private PAIR only. For more information about the PAIR
system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would
like assistance from a USPTO Customer Service Representative or access to the automated
information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678