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
Claims 68 – 87 were pending. Claims 75 and 80 have been amended, and claims 76 and 87 have been canceled. Claims 68 – 75 and 77 – 86 are currently pending and are the subject of this Office Action.
Drawings
Previous objection, withdrawn: the drawings were objected to because the labels of Fig, 1A - 3B, 7B – 10B, 14A – 21, 27A, 27B, 30 – 32C, and 35 are blurry and difficult to read.
In view of the replacement drawings, this objection is withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Previous rejection, withdrawn: claims 76 and 87 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
In view of the cancelation of claims 76 and 87 in the reply of 07/01/2025, this rejection is withdrawn.
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.
Previous rejection, withdrawn: claims 76 and 87 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out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.
In view of the cancelation of claims 76 and 87, this rejection is withdrawn.
New rejection: Claims 75 – 86 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.
Claims 75 and 80 each recites “a co-stimulation at a 3:1 bead-to-T cell ratio”, however, the claims do not define the beads. According to the specification, “T cell(s) produced by co-stimulation with anti-CD3/anti-CD28 coated magnetic beads at a ratio of 3:1 (bead:T cell ratio)” (paragraph 0095, for example); however, “with anti-CD3/anti-CD28 coated magnetic beads” is not recited.
Claims 77 – 79 and 81 – 86 depend from claims 75 and 80, respectively, and thus inherit the deficiencies of claims 75 and 80.
Claim Rejections - 35 USC § 102
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.
(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.
Previous rejection, withdrawn: claims 75, 77, 78, 80, 81, 83, and 84 were rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by BROGDON (WO 2018/175636 A2, published 09/27/2018, see PTO-892: Notice of References Cited of 01/29/2025).
In view of the claim amendments in the reply of 07/01/2025, this rejection is withdrawn.
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.
Previous rejection, withdrawn: claims 68, 70, and 79 were rejected under 35 U.S.C. 103 as being unpatentable over BROGDON in view of ZAZA (Zaza G, Granata S, Caletti C, Signorini L, Stallone G, Lupo A. mTOR inhibition role in cellular mechanisms. Transplantation. 2018 Feb 1;102(2S):S3-16; see PTO-892: Notice of References Cited of 01/29/2025) and DELGOFFE (Delgoffe GM, Powell JD. mTOR: taking cues from the immune microenvironment. Immunology. 2009 Aug;127(4):459-65; see PTO-892 of 01/29/2025).
In view of the claim amendments in the reply of 07/01/2025, this rejection is withdrawn.
Previous rejection, withdrawn: claim 69 was rejected under 35 U.S.C. 103 as being unpatentable over BROGDON in view of ZAZA and DELGOFFE as applied to claims 68, 70, and 79 above, and further in view of PERL (US 2014/0275257 A1, published 09/18/2014; see PTO-892 of 01/29/2025).
In view of the claim amendments in the reply of 07/01/2025, this rejection is withdrawn.
Previous rejection, withdrawn: claim 71 was rejected under 35 U.S.C. 103 as being unpatentable over BROGDON in view of ZAZA and DELGOFFE as applied to claims 68, 70, and 79 above, and further in view of WANG (Wang Y. et al. Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines. British journal of cancer. 2011 Feb;104(4):643-52; see PTO-892 of 01/29/2025) and BEZIAUD (Beziaud L. et al. Rapalogs Efficacy Relies on the Modulation of Antitumor T-cell Immunity. Cancer Res 15 July 2016; 76 (14): 4100–4112; see PTO-892 of 01/29/2025).
In view of the claim amendments in the reply of 07/01/2025, this rejection is withdrawn.
Previous rejection, withdrawn: claim 72 was rejected under 35 U.S.C. 103 as being unpatentable over BROGDON in view of ZAZA and DELGOFFE as applied to claims 68, 70, and 79 above, and further in view of LUNDEMOSE (US 20170043009 A1, published 02/16/2017; see PTO-892 of 01/29/2025).
In view of the claim amendments in the reply of 07/01/2025, this rejection is withdrawn.
Previous rejection, withdrawn: claims 73 and 74 are rejected under 35 U.S.C. 103 as being unpatentable over BROGDON in view of ZAZA and DELGOFFE as applied to claims 68, 70, and 79 above, and further in view of WILKINSON (WO 2018/106885 A1, published 06/14/2025; see PTO-892 of 01/29/2025).
In view of the claim amendments in the reply of 07/01/2025, this rejection is withdrawn.
Previous rejection, withdrawn: claims 82, 85, and 86 were rejected under 35 U.S.C. 103 as being unpatentable over BROGDON as applied to claims 75, 80, 81, 83, and 84 above, and further in view of DEISHER (WO 2018/183927 A1, published 10/04/2018; see PTO-892 of 01/29/2025) and KANE (Kane BJ et al. Pentostatin: an adenosine deaminase inhibitor for the treatment of hairy cell leukemia. Ann Pharmacother. 1992 Jul-Aug;26(7-8):939-47; see PTO-892 of 01/29/2025).
In view of the claim amendments in the reply of 07/01/2025, this rejection is withdrawn.
New rejection: claims 68 – 74 are rejected under 35 U.S.C. 103 as being unpatentable over VOLK (WO 2012/171882 A1, published 12/20/2012; see PTO-892 submitted with this Office Action) in view of KAARTINEN (Kaartinen, T, et al., Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion, Cytotherapy, Volume 19, Issue 6, 2017, Pages 689-702 (see PTO-892), ZAZA, and RAMOS (Ramos, H. J. et al., Reciprocal responsiveness to interleukin-12 and interferon-α specifies human CD8+ effector versus central memory T-cell fates. Blood 2009; 113 (22): 5516–5525; see PTO-892).
Present independent claim 68 is directed to a method for producing manufactured T cells, comprising: inoculating a culture input population of cells comprising T cells from a subject at a cell density in a culture medium comprising temsirolimus and an IL-2 signaling inhibitor; adding IFN-a to said culture medium; incubating said T cells and culture medium for a period of time to yield manufactured T cells.
According to the present specification, “[t]he success of adoptive T cell therapy is dependent in-part upon the in vivo persistence of the T cell population in the host. T cell persistence is a balance determined by both an increase in T cell ability to proliferate and maintain T cell memory and by reduction in T cell propensity to apoptotic cell death” (paragraph 0003).
VOLK is directed to antigen specific CD4+ and CD8+ central-memory T cells for adoptive T cell therapy, and a method for providing such cells (see p. 1, lines 8 – 9). VOLK teaches a method for generation of T cell preparations that are specific for at least one target antigen, comprising the steps of: expanding lymphoid cells in vitro in the presence of a target antigen or peptide fragments thereof in an expansion step, yielding a first T cell preparation; isolating responding cells from the first T cell preparation in an isolation step, yielding a second T cell preparation; culturing, in a culturing step, the cells obtained as second T cell preparation in the presence of a cytokine, preferably interleukin 2 and/or interleukin 7, and i. an inhibitor of the mTOR Complex 1 , preferably rapamycin or a rapamycin analogue, or ii. an inhibitor of interleukin 2 (IL-2) - interleukin-2-receptor (IL-2R) interaction for use in the prevention or therapy of infectious disease or cancer in patients. See claims 1 and 13 – 14.
VOLK teaches that temsirolimus is a preferred mTOR inhibitor, along with rapamycin (see p. 9, line 24 – p. 10, line 1) and that a preferred antibody to inhibit the alpha chain of IL2-receptor complex is Daclizumab (see p. 10, lines 3 – 4).
Thus, VOLK teaches a method for producing manufactured T cells, comprising: inoculating a culture input population of cells comprising T cells from a subject at a cell density in a culture medium comprising temsirolimus or an IL-2 signaling inhibitor. VOLK teaches that modifying IL2-receptor signaling by targeting IL-2 receptor binding or mTor pathway enables superior protective CD4-mediated CD8+ T-cell immunity (see p. 13, lines 10 – 11) and that adoptive T cell therapy is a novel promising therapeutic approach to restore immune competence (see p. 1, lines 18 – 19). Thus, it would have been obvious to use an IL-2 inhibitor, and because temsirolimus targets the mTOR pathway, to use temsirolimus on T cells manufactured for adoptive T-cell therapy.
Although VOLK teaches the culturing of antigen specific CD4+ and CD8+ central-memory T cells for adoptive T cell therapy cells by adding an mTOR inhibitor or an IL-2 inhibitor (and not the addition of the mTOR and IL-2 inhibitors together in the cell culture medium as claimed in present claim 68), VOLK teaches that the use of either inhibitor leads to antigen specific CD4+ and CD8+ central-memory T cells for adoptive T cell therapy.
KAARTINEN is directed to a study concluding that high IL-2 levels led to a decrease in overall generation of early memory T cells by both decreasing central memory T cells and augmenting effectors. See Abstract: Results. Thus, KAARTINEN teaches that low interleukin-2 concentration favors generation of early memory T cells, which reinforces VOLK’s teaching that an IL-2 inhibitor leads to central-memory T cells for adoptive therapy.
ZAZA is directed to the mammalian target of rapamycin inhibitors (mTOR-I), which are drugs widely used in transplant medicine and oncology, and how mTOR-I exert their function. ZAZA discloses how the inhibition of mTOR has a major impact on cellular metabolism by stimulating synthesis of proteins and lipids, inhibiting catabolic processes, such as lysosome biogenesis and autophagy, and controlling cell survival, cytoskeleton organization, lipogenesis, and gluconeogenesis, which are all biological functions essential to guarantee body homeostasis and survival. See abstract. Furthermore, ZAZA discloses that temsirolimus inhibits mTOR. See p. S4, left column, first paragraph. ZAZA also discloses that in the presence of an mTOR inhibitor, cells showed a suppressed IFN-α/β production together with impaired ability to stimulate antigen-specific CD4+ T cell activation. See p. S11, left column, last paragraph.
RAMOS is directed to Multiple innate signals regulate the genesis of effector and memory CD8+ T cells. RAMOS teaches that IFN-α drove the development of T central memory (TCM) cells. See abstract.
Because the cited references teach that the mTOR inhibitor temsirolimus, an IL-2 inhibitor or low levels of IL-2, and IFN-α each help develop T central memory cells for adoptive T-cell therapy, it would have been obvious combine temsirolimus, an IL-2 inhibitor, and IFN-α in a culture medium for the T cells in a method for producing manufactured T cells. There would have been a reasonable expectation of success given that mTOR inhibition by temsirolimus, IL-2 signaling inhibition, and IFN-α have been known to successfully lead to T central memory cells that are effective in T cell therapy as evidenced by the applied prior art.
Regarding claim 69, because VOLK does not expressly state that anti-CD3/anti-CD28 co- stimulation is performed, it is assumed that no anti-CD3/anti-CD28 co- stimulation is performed in VOLK’s T cell preparation.
Regarding claim 70, because ZAZA discloses that IL-2 activates mTOR, which is the opposite function of temsirolimus, and claim 68, from which claim 70 depends, aims to inhibit IL-2, it would have been obvious that the culture medium does not contain IL-2 and no IL-2 is added to the culture medium.
Regarding claim 71, VOLK discloses that the culturing step lasts between 10 and 25 days, between 15 and 21 days, or about 18 days. See claim 5. Although the claimed period of time differs slightly from that of VOLK, the claimed period of time can be determined by routine experimentation. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”. See MPEP 2144.05 (I) and (II).
Regarding claim 72, RAMOS discloses culturing T cells with IFN-α (rhIFN-α(A) [1000 U/mL]. See Methods: Purification and in vitro cultures of human CD8+ T cells
Regarding claims 73 – 74, VOLK discloses that the inhibitor of IL-2-IL-2R interaction is a monoclonal antibody targeting CD25, particularly Daclizumab or Basiliximab. See claim 3.
New rejection: claims 75 and 77 – 81 are rejected under 35 U.S.C. 103 as being unpatentable over VOLK in view of ZAZA, FENG (Feng, X. et al. Rapamycin is highly effective in murine models of immune-mediated bone marrow failure. Haematologica 2017;102(10):1691-1703; see PTO-892 submitted with this Office Action) and BRAHMANDAM (WO 2019/090004 A1, filed 11/01/2018; see PTO-892).
Present independent claim 75 is directed to a composition comprising manufactured T cells, wherein at least of portion of the manufactured T cells have the following property: secretion of low levels of the inflammatory cytokines IFN-γ and TNF-α at the end of six days in culture, as defined by < 100 pg/ml per 1 x 106 cells per 24 hours contained in a culture supernatant after a co-stimulation at a 3:1 bead-to-T cell ratio.
Present independent claim 80 is directed to a method of treating cancer in a subject in need thereof, comprising: administering to said subject a composition comprising manufactured T cells at a therapeutically effective dose, wherein at least of portion of the manufactured T cells have the following property: secretion of low levels of the inflammatory cytokines IFN-γ and TNF-α at the end of six days in culture, as defined by < 100 pg/ml per 1 x 106 cells per 24 hours contained in a culture supernatant after a co-stimulation at a 3:1 bead-to-T cell ratio.
FENG is directed to a strategy that involves a combination of immune activation and the immunosuppressive mTOR inhibitor rapamycin. See abstract. FENG teaches how the mTOR inhibitor rapamycin modulates T-cell function (see p. 1695, right column) and that modulation of mTOR activity and its downstream signaling molecules is key to the therapeutic efficacy of rapamycin (see Discussion, first paragraph, p. 1701).
FENG teaches that plasma from mice were treated with rapamycin and analyzed for T-cell-related cytokines, with the results showing IFNγ and TNFα each being less than < 100 pg/ml. See Figure 3E.
Furthermore, FENG teaches that lymph node (LN) cells (2.0 x 106) were cultured, and T cells were stimulated with anti-CD3 (1 µg/ml) and CD28 antibodies (2 µg/ml). See Supplemental Materials and Methods , p. 4, at the end of FENG.
Although FENG does not co-stimulate at exactly 3:1 bead to T-cell ratio, FENG teaches the co-stimulation method and thus, this ratio can be determined by routine optimization. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of Americav.Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)”. See MPEP 2144.05 (I) and (II).
Because VOLK teaches manufactured T cells by cultured in the presence of temsirolimus or an IL-2 signaling inhibitor (because targeting IL-2 receptor binding or mTor pathway enables superior protective CD4-mediated CD8+ T-cell immunity) for administration to a patient (see p. 7, lines 7 – 8), ZAZA discloses that temsirolimus inhibits the mTOR pathway and leads to cellular growth but suppresses IFN-α, which may be beneficial for effector T cells, and FENG discloses plasma cells treated with mTOR-inhibitor rapamycin with properties of IFN-γ and TNF-α secreted less than < 100 pg/ml, it would have been obvious to arrive to a T-cell composition having the properties of claim 75 and 80 in a method of treating cancer of claim 80. There would have been a reasonable expectation of success given that the inhibition of mTOR is known to lead to T-cells having low levels of IFN-γ and TNF-α and known to be effective in the manufacture of T cells for T-cell therapy as evidenced by the applied prior art.
BRAHMANDAM is directed to a method for producing a composition of engineered cells, the method comprising: (a) incubating, under stimulating conditions, an input composition comprising primary human T cells, said stimulating conditions comprising the presence of (i) a stimulatory reagent capable of activating one or more intracellular signaling domains of one or more components of a TCR complex and/or one or more intracellular signaling domains of one or more costimulatory molecules and (ii) an agent that inhibits mTOR activity. See claim 1. Furthermore, BRAHMANDAM teaches that the agent that inhibits mTOR activity is rapamycin, temsirolimus. See claim 33.
BRAHMANDAN discloses the formulating cells of the output composition for cryopreservation and/or administration to a subject, optionally in the presence of a pharmaceutically acceptable excipient. See claim 74.
Regarding claims 77 and 78, BRAHMANDAM teaches that the portion, percentage, and/or amount of cells that express one or more markers of exhaustion in the output composition is or is at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% less than the portion, percentage, and/or amount of cells that express the one or more markers in an output composition produced by the exemplary, alternative process and that the one or more markers of exhaustion is or includes CTLA-4 and PD-1. See paragraph 0317. Thus, an amount of cells that express CTLA-4 or PD-1 in the disclosed output composition is at least 90% less than the amount of cells that express CTLA-4 in an output composition produced by the exemplary, alternative process would be equivalent to 10% or less of T cells expressing CTLA4 of claim 77 or PD1 of claim 78. BRAHMANDAM also teaches that presence of surface expression is detected by flow cytometry. See paragraph 0560.
Regarding claim 79, BRAHMANDAM teaches an agent that inhibits mTOR activity inhibits at least one activity of an mTOR protein, such as, for example, the serine/threonine protein kinase activity on at least one of its substrates, e.g., p70S6 kinase. See paragraph 0328.
Regarding claim 84, BRAHMANDAM teaches that the disease, disorder or condition is a tumor or a cancer such as multiple myeloma (MM). See paragraphs 0033 and 0486.
Regarding claim 83, BRAHMANDAM teaches that the dose of cells comprises between at or about 2 x 105 of the cells/kg and at or about 2 x 106 of the cells/kg, such as between at or about 4 x 105 of the cells/kg and at or about 1 x 106 of the cells/kg or between at or about 6 x 105 of the cells/kg and at or about 8 x 105 of the cells/kg. See paragraph 0505.
Thus, because VOLK and ZAZA teach a method of producing manufactured T cells in a culture medium with temsirolimus and an IL-2 signaling inhibitor and adding IFN-α as discussed above, FENG teaches T cells with a secretion of low levels of the inflammatory cytokines IFN-γ and TNF-α, as defined by < 100 pg/ml per 1 x 106 cells, and BRAHMANDAM teaches the culturing of cells with mTOR inhibitors, it would have been obvious to combine the methods of the cited references to arrive to the inventions of claims 77 – 81, 83 and 84.
New rejection: claims 82, 85, and 86 are rejected under 35 U.S.C. 103 as being unpatentable over VOLK in view of ZAZA, FENG and BRAHMANDAM as applied to claims 77 – 81, 83 and 84 above, and further in view of DEISHER and KANE.
The teachings of VOLK, ZAZA, FENG and BRAHMANDAM are discussed above and fully incorporated here.
DEISHER is directed to novel therapeutic compositions and methods that keep cellular immunotherapies in the circulation or at the site of injection for extended periods of time without resorting to the use of cytotoxic preconditioning. See abstract.
KANE is directed to pharmacology, pharmacokinetics, adverse effects, and various dosage regimens of pentostatin. See Abstract: Objective, p. 939.
While VOLK discloses a T cell preparation for use in the prevention or therapy of cancer (see claim 13), VOLK does not disclose that the immune depletion regimen comprises: administering pentostatin to said subject of claim 82 or that the pentostatin is administered to said subject at a dose between 1-4 mg/m2 of claim 85.
Regarding claim 82, DEISHER discloses that prevailing thought has been that preconditioning enhanced adoptive cell transfer or therapy (ACT) effectiveness by eliminating Tregs and that pentostatin and cyclophosphamide are preconditioning agents. See paragraphs [003] and [0052].
Because VOLK in view of ZAZA discloses a T cell preparation for use in the prevention or therapy of cancer and FENG discloses T cells having the property of claim 80 (from which claim 82 depend; as discussed above), and DEISHER teaches that the administration of pentostatin and cyclophosphamide enhances adoptive cell transfer or therapy (ACT) effectiveness, it would have been obvious to one having ordinary skill in the art to modify the administration of VOLK/ZAZA’s T cell preparation to add pentostatin and cyclophosphamide to arrive to the invention of claim 82.
Regarding claim 85, KANE discloses the administration of pentostatin at a dose between 1-4 mg/m2. See Abstract: Data synthesis, p. 939.
Regarding claim 86, DEISHER discloses that cyclophosphamide may be administered at about 200 to about 2100 mg/m2. Considering that the average human is 1.79 m2, DEISHER discloses the claimed range.
Response to Arguments
On p. 11, last paragraph; p. 14, second paragraph; p. 16, second paragraph; p. 18, second paragraph; and p. 20, second paragraph of the reply of 07/01/2025, Applicant argues that “Brogdon teaches activation of IL-2 signaling in the manufacture of CAR T cells”. BROGDON was mainly applied because of its teachings regarding the manufacturing of T cells recited in claims 75 and 80 prior to the claim amendments of 07/01/2025. In view of the claim amendments to independent claims 75 and 80, BROGDON is no longer applied. New rejections have been applied in the 103 rejection above.
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.
Previous rejection, maintained in modified form: claims 68 – 75 and 77 – 86 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 10, 13, 17 – 23, 31, and 402 – 406 of copending Application No. 17/984,810 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because copending claim 1 recites a method for producing manufactured T cells, comprising: inoculating a culture input population of cells from a subject at a cell density in a culture medium comprising temsirolimus and an IL-2 signaling inhibitor, wherein the culture input population of cells comprises T cells; incubating said culture input population of cells in the culture medium for a first period of time; adding IFN-α,IL-7, and IL-15 to the culture medium after the first period of time; incubating said culture input population of cells in the culture medium for a second period of time following addition of IFN-a, IL-7, and IL-15 to yield manufactured T cells, wherein IL-2 is not added to the culture medium at any time during the method, and wherein no anti-CD3/anti-CD28 co-stimulation is performed at any time during the method; and harvesting said manufactured T cells, wherein 5% or less of the manufactured T cells that are CD4+ or CD8+ express CD25 as measured by flow cytometry.
Thus, the copending claims anticipate the present claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
On p. 22 of the reply of 07/01/2025, Applicant states that “[a]lthough Applicant disagrees with the rejection, for the sake of advancing prosecution, Applicant is filing a terminal disclaimer herewith.” However, no terminal disclaimer has been filed. Thus, the provisional rejection over copending Application No. 17/984,810 is maintained.
Conclusion
No claim is allowed.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647