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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 09/29/2025 is acknowledged. The traversal is on the ground(s) that restriction is only proper if the claims of the restricted groups represent a serious burden placed on the Examiner.
Applicant traversed the restriction by asserting restriction is only proper if the claims of the restricted groups are independent or
patentably distinct and there would be a serious burden placed on the Examiner if restriction is not required, and relying on MPEP § 803.
This is not found persuasive because Chapter 800 of MPEP is limited to a discussion of the subject of restriction and double patenting under Title 35 of the United States Code and Title 37 of the Code of Federal Regulations as it relates to national applications filed under 35 U.S.C. 111(a). The discussion of unity of invention under the Patent Cooperation Treaty Articles and Rules as it is applied as an International Searching Authority, International Preliminary Examining Authority, and in applications entering the National Stage under 35 U.S.C. 371 as a Designated or Elected Office in the U.S. Patent and Trademark Office is covered in M.P.E.P. §1850 and is dictated by PCT Rules 13.1 and 13.2. See M.P.E.P. §801. Burden is not a consideration in a finding of lack of inventive unity; rather, according to M.P.E.P. §1850, the only consideration is whether the inventions share a special technical feature.
Applicant further traverses the restriction and asserts that unity of invention does exist between Groups I-II because there is a technical relationship that involves the same special technical feature.
As set forth in the previous office action, while groups I and II share the technical feature of a cell that is genetically engineered to express membrane bound IL-18 and membrane bound IL-21, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Kamiya et al (WO 2018/182511 A1, cited in the IDS filed on 03/07/2024).
The claim recites “feeder cell”. The instant specification defines "feeder cell” as a “supporting cell" and “a cell that does not have the ability to divide due to irradiation, but has metabolic activity so that it produces various metabolites and helps target NK cells proliferate” (p4 ¶2).
Kamiya teach a genetically engineered cell population that are co-cultured with NK immune cells (abstract). Kamiya further teach the genetically engineered cell wherein co-culture of said engineered cell with a population of immune cells results in the activation and expansion of at least one subpopulation of immune cells (claim 1). Kamiya teach the genetically engineered cell expresses membrane bound IL18 and mbIL21 (claims 14 and 16, claims 33-35).
Kamiya also teach coculture of NK cells with irradiated K562 cells expressing mbIL15 and mbIL18 (p31 ¶0076]. Kamiya does not teach the cell expressing mbIL18 and mbIL21 is an irradiated cell.
It would have been obvious to one of ordinary skill in the art to adapt the feeder cell taught by Kamiya, which expresses membrane bound IL18 and mbIL21, with the irradiated feeder cell, also taught by Kamiya.
One of ordinary skill in the art would have been motivated to modify the feeder cell expressing mbIL15 and mbIL18 by irradiating the feeder cell because Llames teach feeder cells provide signals and factors to support the culture of target cells, but must be prevented from overgrowing the culture, and thus feeder cells must be in a nonmultiplying but metabolically active state (p353 col2 ¶2). Llames further teach that feeder cells are often irradiated so that they will not proliferate (p353 ¶1).
One would have had a reasonable expectation of success because Kamiya teach a feeder cell that is irradiated and supports NK expansion and one of ordinary skill in the art would understand that irradiating a feeder cell would is a common practice that would not impair feeder cell function.
Thus the teachings of Kamiya and Llames render obvious the invention as claimed.
The traversal is not found persuasive due to the reasons discussed supra, and the requirement is still deemed proper and is therefore made FINAL.
Claims 1-15 are pending.
Claims 5-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09/29/2025.
Claims 1-4 are examined on the merits.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3 and 4 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Regarding claim 3: The rejected claim depends from claim 1 and recites “the feeder cell includes a nucleic acid encoding mbIL-18 and mbIL-21”.
Claim 1 requires a feeder cell engineered to express mbIL-18 and mbIL-21. The feeder cell of claim 1 must comprise a nucleic acid encoding mbIL-18 and mbIL-21 to be able to express the required proteins.
Thus the limitations recited in claim 3 do not in any way further limit the feeder cell of claim 1.
Regarding claim 4: The rejected claim requires the feeder cell of claim 1 and further comprises the intended use phrase “for culturing a natural killer cell” in the preamble.
MPEP (2111.02 II) states “During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim”.
“for culturing a natural killer cell” does not impart a structural limitation on the feeder cell and is thus not considered to limit the claim.
The only component required in claim 4 is the cell of claim 1. The broadest reasonable interpretation of a composition is the required cells. Thus the limitations recited in claim 4 do not in any way further limit the feeder cell of claim 1.
Appropriate correction is required.
Claim Objections
Claims 1 and 2 are objected to because of the following informalities: grammar and acronyms
Regarding claim 1: The claim recites “A feeder cell for culturing a natural killer (NK) cell, genetically engineered to express membrane bound interleukin-18 (mbIL-18) and membrane bound interleukin-21 (mbIL-21)”.
The following changes are suggested for improved grammar: “A feeder cell for culturing a natural killer (NK) cell, wherein the feeder cell is genetically engineered to express membrane bound interleukin-18 (mbIL-18) and membrane bound interleukin-21 (mbIL-21)”
Regarding claim 2: The claim recites “the feeder cell is at least one selected from the group consisting of K562, RPMI8866, EBV LCL, 721.221, HFWT, and NK-92 cells”.
The following changes are suggested for improved grammar: “the feeder cell is a human chronic myelogenous leukemia cell line (K562 cell), RPMI8866, EBV LCL, 721.221, HFWT, and NK-92 cells” (supported by specification p3 ¶2).
“A human chronic myelogenous leukemia cell line (K562 cell)” is added for additional information on the feeder cell line. “At least one” is removed because it is redundant.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Identifiers (Seq ID NOs) are required for the nucleotide sequences in Table 1 of the instant specification (p18).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Kamiya et al (WO 2018/182511 A1, as cited in the IDS filed on 03/07/2024) in view of Llames et al (Tissue engineering: Part B (2015)21:4).
Regarding claims 1 and 4: The claim recites “feeder cell”. The instant specification defines "feeder cell” as a “supporting cell" and “a cell that does not have the ability to divide due to irradiation, but has metabolic activity so that it produces various metabolites and helps target NK cells proliferate” (p4 ¶2).
Turning to the art, Kamiya teach a genetically engineered cell population that are co-cultured with NK immune cells (abstract). Kamiya further teach the genetically engineered cell wherein co-culture of said engineered cell with a population of immune cells results in the activation and expansion of at least one subpopulation of immune cells (claim 1). Kamiya teach the genetically engineered cell expresses membrane bound IL18 and mbIL21 (claims 14 and 16, claims 33-35).
Kamiya also teach coculture of NK cells with irradiated K562 cells expressing mbIL15 and mbIL18 (p31 ¶0076]. Kamiya does not explicitly teach the feeder cell expressing mbIL18 and mbIL21 is an irradiated cell.
It would have been obvious to one of ordinary skill in the art to adapt the feeder cell taught by Kamiya, which expresses membrane bound IL18 and mbIL21, with the irradiated feeder cell that expresses mbIL15 and mbIL18, also taught by Kamiya.
One of ordinary skill in the art would have been motivated to modify the feeder cell expressing mbIL18 and mbIL21 to use an irradiated feeder cell expressing mbIL18 and mbIL21 because Llames teach feeder cells provide signals and factors to support the culture of target cells, but must be prevented from overgrowing the culture, and thus feeder cells must be in a nonmultiplying but metabolically active state (p353 col2 ¶2). Llames further teach that feeder cells are often irradiated so that they will not proliferate (p353 ¶1).
One would have had a reasonable expectation of success because Kamiya teach a feeder cell that is irradiated and supports NK expansion and one of ordinary skill in the art would understand that irradiating a feeder cell is a common practice that would not impair feeder cell function, but could reasonably be expected to improve feeder cell function by preventing feeder cell overgrowth.
Regarding claim 2: Kamiya further teach the feeder cell is derived from the cell line K562 (claim 6).
Regarding claim 3: As stated supra, Kamiya teach a genetically engineered cell which expresses membrane bound IL18 and mbIL21 (claims 14 and 16, 33-35 and 62-64). For a cell to express a protein the cell must comprise a nucleic acid encoding the protein.
Furthermore, Kamiya teach the cell comprises the nucleic acid sequence encoding mbIL-18 (Seq ID NO:8) and mbIL-21 (Seq ID NO:10) (claims 33-34 and 35-36).
Thus the teachings of Kamiya and Llames render obvious the invention as claimed.
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 1-4 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of copending Application No. 17/996,541 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the disclosure of the reference application would anticipate the disclosure of the instant application if it were available as prior art.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1: Copending claim 1 discloses a feeder cell for culturing natural killer (NK) cells, genetically engineered to express membrane bound interleukin-18 (mbIL-18), membrane bound interleukin-21 (mbIL-21).
Regarding claim 2: Copending claim 2 teaches the feeder cell is selected from the group consisting ofK562, RPMI8866, EBV _LCL, 721.221, HFWT, and NK-92 cells.
Regarding claim 3: Copending claim 3 teaches the feeder cell of comprises a nucleic acid encoding mbIL-18 and mbIL-21.
Regarding claim 4: Copending claim 4 teaches a composition for culturing a natural killer cell comprising the feeder cell.
Thus the disclosure of 17/996,541 would anticipate the instant invention.
Conclusion
No claims are allowed.
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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631