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 .
Claim Status
Claims 1-74, 86-90, 93, 100, and 101 have been cancelled.
Claim 103 has been added.
Claims 75-85, 91-92, 94-99, 102 and 103 are currently pending.
Claims 77, 91-92, 94-99 and 102 have been withdrawn.
Claims 75-76, 78-85 and 103 are being examined in this application.
Election/Restrictions
Applicant’s election without traverse of Group I invention (Claims 75-85, and newly added claim 103) and the “terminally differentiated effector memory T cells” as the species of starting T cells in the reply filed on 7/14/25 is acknowledged. Applicants state that claim 77 does not read on the elected species.
Claims 77, 91-92, 94-99 and 102 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/14/25.
Priority
This application is a CON of 16/339,691 (filed on 04/04/2019; now PAT 11421010), which is a 371 of PCT/US2017/055645 (filed on 10/06/2017), which claims priority to PRO 62/405,796 (filed on 10/07/2016).
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62/405,796 (provisional; hereinafter referred to as ‘796 Application), fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The ‘796 application does not provide support for the instant recited method of culturing T cells in the presence of anti-CD3 and CD80, in the specification and claims.
Thus the instant claims 75-76, 78-85 and 103 do not obtain the priority benefit of the ‘796 provision application. The effective filing date for claims 75-76, 78-85 and 103 is 10/6/2017.
Information Disclosure Statement
The IDS filed on 8/17/23 has been considered. See the attached PTO 1449 form.
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.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification. MPEP 608.01.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Hu et al
Claim(s) 75-76, 78-85 and 103 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Hu et al (Oncoimmunology. Vol.5(12): 1-15; 11/1/2016).
The instant claims recite an in vitro method for generating NKG2D-positive CD8+ T cells comprising:
(a) obtaining a starting population of T cells; and
(b) culturing the starting population of T cells in the presence of anti-CD3 and CD80 to induce NKG2D expression, thereby generating NKG2D+CD8+ T cells.
Hu et al, throughout the reference, teach method of stimulating T-cell using various antibody and/or antigens (e.g. Abstract).
For claims 75-76, 78-83 and 103, Hu et al, teach obtaining splenic CD8+ T cells, and treated the cells first with anti-CD3 microbeads for 24 h, and then treated with CD80-Fc for 1-5 days, which “significantly increased the NKG2D+CD8+ T cell population” (p.2, left col., para 4; Figure 3). The splenocytes used in the reference would contain terminally differentiated effector memory T cells.
For claim 84: The reference also teaches stimulation of STAT3 phosphorylation (e.g. Abstract; p.2, right col.).
For claim 85: The reference also teaches the cells express TCR (e.g. p.2).
Fowler et al
Claim(s) 75-76, 78-82 and 84 is/are rejected under 35 U.S.C. 102 (a)(1)/(a)(2) as being anticipated by Fowler et al (WO 2005/003335; 1/13/2005; filed on 6/10/2004 or earlier).
Fowler et al, throughout the reference, teach methods of enriching desired T cells. (e.g. Abstract).
For claim 75, Fowler et al, teach co-stimulation of T lymphocytes with two different stimulants including anti-CD3 and anti-CD28, or another “antibodies, polypeptides, polynucleotides, small molecules (e.g. p.7, lines 9+; p.23, lines 24+). The reference also teaches co-activation or optimal co-stimulation of CD3 and/or CD28 receptors of T cell (e.g. p.29, lines 11+). The reference also teaches “optimal activation and proliferation requires costimulation of CD28 receptors on T cells with anti-CD28 or B7 molecules (CD80 and CD86)” (p.29, lines 19+). The reference also teaches the T cells are CD8+ (e.g. p.29, lines 5+).
As evidenced by the instant specification (instant spec., [0048]) that stimulation of CD28 in CD8+ T Cell would lead to NKG2D receptor expression, the reference’s teaching of co-stimulation of CD3 and CD28 would necessarily generate NKG2D+CD8+ cells. Thus, the reference’s teaching reads on the claimed method.
For claims 76 and 82, the reference teaches treating T Cells with anti-CD3 antibodies that maybe immobilized on a solid support, such as beads (e.g. p.29, lines 10+; p.57, lines 5+), and co-stimulation with CD80 (e.g. p.29, lines 20+; p.3, line 3).
For claims 78-79, the reference also teaches the T cells are CD8+ (e.g. p.29, lines 5+).
For claims 80-81, the reference teaches treating starting T cells with anti-CD3 antibodies for 2 days (e.g. p.57, lines 5+) and also teaches co-stimulation with ligand for CD28 for at least 1-2 days as “proliferation of the cells does not appreciably take place within about 1-2 days after commencement of the cultivation…” (p. 54, lines 2+), which reads on the instant claimed 12-48hrs stimulation period.
For claims 84, as evidenced by the instant specification, activation of CD28 receptor through CD80 would lead to STAT3 phosphorylation (Instant spec., [0049]; [0061]). Thus, the reference’s teaching of co-stimulating with CD80 would necessarily lead to STAT3 stimulation.
Claim Rejections - 35 USC § 103
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.
Fowler, Haile and Ramsborg
Claim(s) 75-76, 78-82, 83, 84, 85 and 103 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fowler et al (WO 2005/003335; 1/13/2005; filed on 6/10/2004 or earlier), in view of Haile et al (Journal of Immunology. Vol.191 (5): 2829-2836; 9/1/2013) and Ramsborg et al (WO2015164675; 10/29/2015).
Fowler et al, throughout the reference, teach methods of enriching desired T cells (e.g. Abstract) as discussed supra.
Fowler et al, do not explicitly teach using CD80-Fc recombinant protein as recited in claim 83, further engineering the T cells to express CAR with tumor associated antigen of claim 85, and the starting T cells are terminally differentiated effector memory T cells as recited in claim 103.
However, Haile et al., throughout the reference teach using recombinant CD80-Fc for T cell activation (e.g. Abstract). The reference also teaches CD80-Fc is more efficacious and used in co-stimulation of CD28 (Abstract; p.2, para 1; pp.3-4, bridging para; p.9, para 2).
Ramsborg et al., throughout the reference teach engineering T Cells for adoptive therapy (e.g. Abstract). The reference teaches isolation and/or enrichment for desired T cell subtypes including “terminally differentiated effector memory T cells (e.g. [0084]). The reference also teaches engineered cells for therapeutic use including ones that “express genetically engineered antigen receptors, such as… TCRs… and … CARs” (e.g. [0004]; [0045]), and the CAR can bidn to a cancer related antigen (e.g. [0235]).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use a recombinant CD80-Fc (instead of CD80) to co-stimulate T cells, because using CD80 to stimulate T cells is known and routine in the art as taught by Fowler, and using recombinant CD80 such as CD80-Fc is also known and routinely used in the art to stimulate T cells (through co-stimulation) via CD28 receptor as taught by Haile. Thus, it would have been obvious to one of ordinary skill in the art to apply the standard technique of using CD80-Fc to co-stimulate T cells as taught by Haile, to improve the efficacy of T cell activation.
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to select terminally differentiated effector memory T cells as the starting T cell population to make desired engineered cells expressing CAR (with specific receptors), because various T cells subtypes are known and routinely used in engineering T cells as taught by Ramsborg. Thus, it would have been obvious to one of ordinary skill in the art to apply the standard technique of enriching or isolate desired T cell subtypes such as the effector memory T cells, and engineer the selected T cells to express CAR with desired receptor such as for cancer related ligands, as taught by Ramsborg.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since Fowler, Haile and Ramsborg all teach method of using T cells including enrichment/isolation, co-stimulation, and genetic engineering are routine and known in the art.
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 75-76, 78-85 and 103 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 21, 23, 24 and 30 of U.S. Patent No. 1,1421,010 (hereinafter referred to as ‘010 Patent) in view of Fowler et al (WO 2005/003335; 1/13/2005; filed on 6/10/2004 or earlier) and Ramsborg et al (WO2015164675; 10/29/2015).
The ‘010 Patent claims the following:
10. A method of treating a cancer in a subject comprising administering an effective amount of T cells engineered to express the nucleic acid encoding the heterodimer membrane-anchored IL-12 of claim 1 to the subject.
14. The method of claim 10, wherein administering the T cells induces expression of NKG2D and/or NKG2D ligands.
21. The method of claim 10, wherein the T cells are CD8+ T cells.
22. The method of claim 10, wherein the T cells are further engineered to express chimeric antigen receptor (CAR) having antigenic specificity for a tumor-associated antigen.
23. The method of claim 10, wherein the T cells are activated with anti-CD3 and CD80-Fc recombinant protein.
30. The method of claim 10, wherein administering the T cells induces expression of co stimulatory receptor CD28 and/or CD80.
The ‘010 Patent does not claim obtaining a starting population of T cells (including the terminally differentiated effector memory T cells), “culturing… in the presence of anti-CD3 and CD80”, and specific culturing duration, as well as engineered T cells with CAR.
However, Fowler et al, throughout the reference, teach methods of enriching desired T cells. (e.g. Abstract). Fowler also teaches co-stimulation of T lymphocytes with two different stimulants including anti-CD3 and anti-CD28, or another “antibodies, polypeptides, polynucleotides, small molecules (e.g. p.7, lines 9+; p.23, lines 24+). The reference also teaches co-activation or optimal co-stimulation of CD3 and/or CD28 receptors of T cell (e.g. p.29, lines 11+). The reference also teaches “optimal activation and proliferation requires costimulation of CD28 receptors on T cells with anti-CD28 or B7 molecules (CD80 and CD86)” (p.29, lines 19+). The reference also teaches the T cells are CD8+ (e.g. p.29, lines 5+).
Ramsborg et al., throughout the reference teach engineering T Cells for adoptive therapy (e.g. Abstract). The reference teaches isolation and/or enrichment for desired T cell subtypes including “terminally differentiated effector memory T cells (e.g. [0084]). The reference also teaches engineered cells for therapeutic use including ones that “express genetically engineered antigen receptors, such as… TCRs… and … CARs” (e.g. [0004]; [0045]), and the CAR can bidn to a cancer related antigen (e.g. [0235]).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to use a recombinant CD80-Fc and anti-CD3 antibody to co-stimulate T cells, because using CD80 and anti-CD3 to stimulate or enrich for T cells is known and routine in the art as taught by Fowler.
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to select terminally differentiated effector memory T cells as the starting T cell population to make desired engineered cells expressing CAR (with specific receptors), because various T cells subtypes are known and routinely used in engineering T cells as taught by Ramsborg. Thus, it would have been obvious to one of ordinary skill in the art to apply the standard technique of enriching or isolate desired T cell subtypes such as the effector memory T cells, and engineer the selected T cells to express CAR with desired receptor such as for cancer related ligands, as taught by Ramsborg.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since Fowler and Ramsborg all teach method of using T cells including enrichment/isolation, co-stimulation, and genetic engineering are routine and known in the art.
Conclusion and Correspondence
No claims are allowed.
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/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
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