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 1-8 are pending and are under examination.
Information Disclosure Statement
The information disclosure statement has been considered.
Claim Rejections - 35 USC § 112
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 6 and 8 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. In this case, claim 6 depends from clam 1 which recites aa composition comprising both (a) CAR T-cells and (b) early apoptotic cells or an early apoptotic cell supernatant, the CAR T-cell t and early apoptotic cells or an early apoptotic cell supernatant are in the same composition, such that the limitation in claim 6 that recites separate compositions fails to include all the limitations upon which it depends. Then with respect to claim 8, which recites the composition of claim 7, which comprises the composition of claim 1 and a further agent, a similar issues arises because the three components of claim 7 are in the same composition, such that claim 8 which also recites separate compositions also fails to include all the limitations 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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over June et al (WO 2014/011984 A1, IDS), Mevorach (US 2005/0202098, IDS) and Pupjalis et al (Griffith et al (I, 35(4):456-466, 2011).
June et al teach a CAR T cell cancer therapy composition for treating cancer patients and that such patients can develop cytokine release syndrome and treating the cytokine release syndrome (CRS) using one or more of a steroid, a TNF alpha inhibitor and an IL-6 inhibitor (see entire document, e.g., abstract, pages 32-33, examples and claims). June et al teach using an IL-6 antibody inhibitor to treat CRS where the patient maintained efficacy of the CAR T cell therapy (see page 36).
Mevorach teaches a composition of apoptotic, dying monocytes from peripheral blood, to suppress the pathological immune response for use in methods of treating patients with a disease characterized by a pathological immune response (see entire document, e.g. abstract, pages 7-10 and claims). Mevorach teaches inducing monocyte apoptosis for 12 hours to obtain a preparation wherein more than 70 percent are annexin positive and less than 5 percent are positive for propidium iodide (see page 5 and Figure 3).
Griffith et al teach that apoptotic lymphocytes (which are peripheral blood cells having a round nucleus or PBMCs) produce the immunosuppressive cytokines IL-10 and TGF-β (see page 4). Griffith et al teach that cells very early in apoptosis (<2 hours) or late-stage apoptosis (>12 hours) they are immunogenic, while 4-8 hrs of apoptosis is optimum for a tolerogenic response (see pages 5-6).
Accordingly, it would have been prima facie obvious to make a composition comprising CAR T cells and a pharmaceutically acceptable excipient and apoptotic autologous or third party donor PMBCs, that treat pathological immune responses, that are more than 70 percent annexin positive and less than 5 percent positive for propidium iodide or a supernatant thereof because such a composition would combine the cancer fighting ability of the CAR T cells with the apoptotic autologous or third party donor PMBCs which can reduce any pathological immune response such as cytokine release syndrome (CRS) cause by the CAR T cells.
Notably, CRS in a cancer patient being treated with CAR T cells may worsen patient outcome or even cause death, so one of skill in the art would have been motivated to make such compositions to test and develop better cancer therapies and as both compositions could be easily mixed, there was motivation to make such compositions and a reasonable expectation of success. Claim 6 is included because before the CAR T cells and a pharmaceutically acceptable excipient and apoptotic autologous or third-party donor PMBCs, that treat pathological immune responses, that are more than 70 percent annexin positive and less than 5 percent positive for propidium iodide or a supernatant thereof are in the same composition, they originated in separate compositions.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, absent a showing otherwise.
Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over June et al (WO 2014/011984 A1, IDS), Mevorach (US 2005/0202098, IDS), Pupjalis et al (Griffith et al (I, 35(4):456-466, 2011, IDS), Tisoncik et al (MMBR, 76(1):16-32, 2012, IDS) and Inoue et al (Shock, 36(1):38-44, 2011, IDS).
June et al teach treating cancer patients with a CAR T cell cancer therapy and that such patients can develop cytokine release syndrome and treating the cytokine release syndrome (CRS) using one or more of a steroid, a TNF alpha inhibitor and an IL-6 inhibitor (see entire document, e.g., abstract, pages 32-33, examples and claims). June et al teach using an IL-6 antibody inhibitor to treat CRS where the patient maintained efficacy of the CAR T cell therapy (see page 36).
Mevorach teaches methods of treating patients with a disease characterized by a pathological immune response, with apoptotic, dying monocytes from peripheral blood, to suppress the pathological immune response (see entire document, e.g. abstract, pages 7-10 and claims). Mevorach teaches inducing monocyte apoptosis for 12 hours to obtain a preparation wherein more than 70 percent are annexin positive and less than 5 percent are positive for propidium iodide (see page 5 and Figure 3).
Griffith et al teach that apoptotic lymphocytes (which are peripheral blood cells having a round nucleus or PBMCs) produce the immunosuppressive cytokines IL-10 and TGF-β (see page 4). Griffith et al teach that cells very early in apoptosis (<2 hours) or late-stage apoptosis (>12 hours) they are immunogenic, while 4-8 hrs of apoptosis is optimum for a tolerogenic response (see pages 5-6).
Tisoncik et al teach that sepsis can cause CRS with the cytokines TNF and later released IL-6 being two cytokines implicated in the cytokine storm (see page 20). Tisoncik et al teach that steroids by themselves are not effective in treatment and can worsen the outcome (see page 26).
Inoue et al teach that CTLA-4 expression increases on regulatory T cells during sepsis and that the correct dose of anti-CTLA-4 improved survival (see abstract).
Accordingly, it would have been prima facie obvious to make a composition comprising CAR T cells and a pharmaceutically acceptable excipient and apoptotic autologous or third party donor PMBCs, that treat pathological immune responses, that are more than 70 percent annexin positive and less than 5 percent positive for propidium iodide or a supernatant thereof along with an anti-CTLA blocking agents because such a composition would combine the cancer fighting ability of the CAR T cells with the apoptotic autologous or third party donor PMBCs along with anti-CTLA-4 which can reduce any pathological immune response such as cytokine release syndrome (CRS) cause by the CAR T cells and sepsis.
Notably, CRS in a cancer patient with sepsis being treated with CAR T cells may worsen patient outcome or even cause death, so one of skill in the art would have been motivated to make such compositions to test and develop better cancer therapies and as the separate compositions could be easily mixed, there was motivation to make such compositions and a reasonable expectation of success. Claims 6 and 8 are included because before the CAR T cells and a pharmaceutically acceptable excipient, apoptotic autologous or third-party donor PMBCs, that treat pathological immune responses, that are more than 70 percent annexin positive and less than 5 percent positive for propidium iodide or a supernatant thereof and anti-CTLA-4 are in the same composition, they originated in separate compositions.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, absent a showing otherwise.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-8 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-22 of US Patent 10,857,181, IDS in view of June et al (WO 2014/011984 A1, IDS), Mevorach (US 2005/0202098, IDS), Pupjalis et al (Griffith et al (I, 35(4):456-466, 2011, IDS), Tisoncik et al (MMBR, 76(1):16-32, 2012, IDS) and Inoue et al (Shock, 36(1):38-44, 2011, IDS). Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons:
In this case, the claims recite compositions of early apoptotic cells that could be used in methods of administering early apoptotic PBMC cells for treating, preventing, inhibiting, reducing the incidence of, ameliorating, or alleviating sepsis, or treating cancer or CRS, in a subject in need, comprising the step of administering a composition comprising an apoptotic cell population to said subject (see claims 10-15).
June et al teach treating cancer patients with a CAR T cell cancer therapy and that such patients can develop cytokine release syndrome and treating the cytokine release syndrome (CRS) using one or more of a steroid, a TNF alpha inhibitor and an IL-6 inhibitor (see entire document, e.g., abstract, pages 32-33, examples and claims). June et al teach using an IL-6 antibody inhibitor to treat CRS where the patient maintained efficacy of the CAR T cell therapy (see page 36).
Mevorach teaches methods of treating patients with a disease characterized by a pathological immune response, with apoptotic, dying monocytes from peripheral blood, to suppress the pathological immune response (see entire document, e.g. abstract, pages 7-10 and claims). Mevorach teaches inducing monocyte apoptosis for 12 hours to obtain a preparation wherein more than 70 percent are annexin positive and less than 5 percent are positive for propidium iodide (see page 5 and Figure 3).
Griffith et al teach that apoptotic lymphocytes (which are peripheral blood cells having a round nucleus or PBMCs) produce the immunosuppressive cytokines IL-10 and TGF-β (see page 4). Griffith et al teach that cells very early in apoptosis (<2 hours) or late-stage apoptosis (>12 hours) they are immunogenic, while 4-8 hrs of apoptosis is optimum for a tolerogenic response (see pages 5-6).
Tisoncik et al teach that sepsis can cause CRS with the cytokines TNF and later released IL-6 being two cytokines implicated in the cytokine storm (see page 20). Tisoncik et al teach that steroids by themselves are not effective in treatment and can worsen the outcome (see page 26).
Inoue et al teach that CTLA-4 expression increases on regulatory T cells during sepsis and that the correct dose of anti-CTLA-4 improved survival (see abstract).
Accordingly, it would have been obvious to make a composition comprising early apoptotic cells of the claims and CAR T cells and a pharmaceutically acceptable excipient wherein the early apoptotic cells are apoptotic autologous or third party donor PMBCs, that treat pathological immune responses, that are more than 70 percent annexin positive and less than 5 percent positive for propidium iodide or a supernatant thereof along with an anti-CTLA blocking agents because such a composition would combine the cancer fighting ability of the CAR T cells with the apoptotic autologous or third party donor PMBCs along with anti-CTLA-4 which can reduce any pathological immune response such as cytokine release syndrome (CRS) cause by the CAR T cells and sepsis.
Notably, CRS in a cancer patient with sepsis being treated with CAR T cells may worsen patient outcome or even cause death, so one of skill in the art would have been motivated to make such compositions to test and develop better cancer therapies and as the separate compositions could be easily mixed, there was motivation to make such compositions and a reasonable expectation of success. Claims 6 and 8 are included because before the CAR T cells and a pharmaceutically acceptable excipient, apoptotic autologous or third-party donor PMBCs, that treat pathological immune responses, that are more than 70 percent annexin positive and less than 5 percent positive for propidium iodide or a supernatant thereof and anti-CTLA-4 are in the same composition, they originated in separate compositions.
Accordingly, the claimed inventions are so substantially similar that any minor differences in the subject matter claimed in the instant application would be seen as an obvious variation of the subject matter claimed in the patents in view of the prior art recited.
Claims 1-8 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-17 of US Patent 11,717,539 in view of June et al (WO 2014/011984 A1, IDS), Mevorach (US 2005/0202098, IDS), Pupjalis et al (Griffith et al (I, 35(4):456-466, 2011, IDS), Tisoncik et al (MMBR, 76(1):16-32, 2012, IDS) and Inoue et al (Shock, 36(1):38-44, 2011, IDS). Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons:
In this case, the claims recite methods that administer compositions of early apoptotic cells or an early apoptotic cell supernatant and a pharmaceutically acceptable excipient, wherein said early apoptotic cells are >40% Annexin V+ and < 15% propidium iodide+, and wherein said early apoptotic cells are peripheral blood mononuclear cells concurrently with CAR T cells (see claims 16).
June et al teach treating cancer patients with a CAR T cell cancer therapy and that such patients can develop cytokine release syndrome and treating the cytokine release syndrome (CRS) using one or more of a steroid, a TNF alpha inhibitor and an IL-6 inhibitor (see entire document, e.g., abstract, pages 32-33, examples and claims). June et al teach using an IL-6 antibody inhibitor to treat CRS where the patient maintained efficacy of the CAR T cell therapy (see page 36).
Mevorach teaches methods of treating patients with a disease characterized by a pathological immune response, with apoptotic, dying monocytes from peripheral blood, to suppress the pathological immune response (see entire document, e.g. abstract, pages 7-10 and claims). Mevorach teaches inducing monocyte apoptosis for 12 hours to obtain a preparation wherein more than 70 percent are annexin positive and less than 5 percent are positive for propidium iodide (see page 5 and Figure 3).
Griffith et al teach that apoptotic lymphocytes (which are peripheral blood cells having a round nucleus or PBMCs) produce the immunosuppressive cytokines IL-10 and TGF-β (see page 4). Griffith et al teach that cells very early in apoptosis (<2 hours) or late-stage apoptosis (>12 hours) they are immunogenic, while 4-8 hrs of apoptosis is optimum for a tolerogenic response (see pages 5-6).
Tisoncik et al teach that sepsis can cause CRS with the cytokines TNF and later released IL-6 being two cytokines implicated in the cytokine storm (see page 20). Tisoncik et al teach that steroids by themselves are not effective in treatment and can worsen the outcome (see page 26).
Inoue et al teach that CTLA-4 expression increases on regulatory T cells during sepsis and that the correct dose of anti-CTLA-4 improved survival (see abstract).
Accordingly, it would have been obvious to make a composition comprising early apoptotic cells of the claims and CAR T cells and a pharmaceutically acceptable excipient wherein the early apoptotic cells are apoptotic autologous or third party donor PMBCs, that treat pathological immune responses, that are more than 70 percent annexin positive and less than 5 percent positive for propidium iodide or a supernatant thereof along with an anti-CTLA blocking agents because such a composition would combine the cancer fighting ability of the CAR T cells with the apoptotic autologous or third party donor PMBCs along with anti-CTLA-4 which can reduce any pathological immune response such as cytokine release syndrome (CRS) cause by the CAR T cells and sepsis.
Notably, CRS in a cancer patient with sepsis being treated with CAR T cells may worsen patient outcome or even cause death, so one of skill in the art would have been motivated to make such compositions to test and develop better cancer therapies and as the separate compositions could be easily mixed, there was motivation to make such compositions and a reasonable expectation of success. Claims 6 and 8 are included because before the CAR T cells and a pharmaceutically acceptable excipient, apoptotic autologous or third-party donor PMBCs, that treat pathological immune responses, that are more than 70 percent annexin positive and less than 5 percent positive for propidium iodide or a supernatant thereof and anti-CTLA-4 are in the same composition, they originated in separate compositions.
Accordingly, the claimed inventions are so substantially similar that any minor differences in the subject matter claimed in the instant application would be seen as an obvious variation of the subject matter claimed in the patents in view of the prior art recited.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brad Duffy whose telephone number is (571) 272-9935. The examiner works a flexible schedule.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Julie Wu can be reached on (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Respectfully,
Brad Duffy
571-272-9935
/Brad Duffy/
Primary Examiner, Art Unit 1643
August 21, 2025