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 .
Application Status
This action is written in response to applicant’s correspondence received on 7/20/2022. Claims 1-10, 27-31, and 38-42 are pending. Claims 5, 9, 27, 29, 38, and 41 have been amended. Claims 11-26, 32-37, and 43-55 have been cancelled. Claims 1-10 and 27-31 are withdrawn from consideration, as they are drawn to a nonelected invention. Claims 38-42 are currently under examination.
Election/Restrictions
Applicant’s election of invention Group V on 8/26/2025, drawn to claims 38-42, is acknowledged. Claims 1-10 and 27-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 8/26/2025. The Applicant argues that it would not constitute a burden to search the entire application and its claims. This argument is not found persuasive because the requirement for restriction was based on a lack of unity of invention, and not based upon a rationale of search burden. Furthermore, even the restriction were based upon a rationale directed to search burden, the Applicant has not offered an argument for why no burden exists, and has simply stated that no burden exists. The arguments are therefore not persuasive, the restriction deemed proper and therefore FINAL.
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’s electronic filing system (see Section I.1 of the Legal Framework for EFS-Web or Patent Center (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), 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 EFS-Web or Patent Center 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 EFS-Web or Patent Center 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 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
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 incorporation-by-reference paragraph, 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 § 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.
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.
Claims 38 and 40 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Roybal (Roybal KT et al. Cell. 2016 Oct 6;167(2):419-432.e16). The rejection is further evidenced by Osinalde (Osinalde N et al. Mol Cell Proteomics. 2016 Jun;15(6):2076-92).
Regarding claim 38, as an initial matter, Roybal teaches the cell of claim 1 which is recited in claim 38 (SynNotch cells programmed to control the expression of a cytokine, Abstract, page 5 paragraphs 3-4 to page 6 first two paragraphs). Roybal teaches administering such cells to a mouse (an “individual” as defined by the specification at paragraph 41, Figure 6 of Roybal and page 9 final paragraphs to page 10 first paragraph). Thus, Roybal teaches the method of claim 38 and its steps, and therefore inherently anticipates the claim. Furthermore, with regards to the intended use language of the preamble of the claim, Roybal teaches that “the activity of the T cells was highly specific to the target tumor,” and therefore teaches increasing the activity of a target cell. Furthermore, the fact that the cell circuits taught by Roybal were designed with IL-2 expression, a cytokine known to promote T cell proliferation as evidenced by Osinalde (Abstract, page 2085, left column, second paragraph), the method taught by Roybal reasonably inherently includes the increased proliferation of a target immune cell.
Regarding claim 40, as discussed above, Roybal anticipates the method of claim 38, to include the production of the cytokine IL-2 (see rejection f claim 38, above). Furthermore, as IL-2 promotes the proliferation of endogenous immune cells as evidenced by Osinalde (Abstract, page 2085, left column, second paragraph), the method taught by Roybal inherently includes the claim limitation wherein the target immune cell is an endogenous immune cell because the method of Roybal includes the induced expression of the T-cell proliferating IL-2 cytokine (rejection of claim 38, above). Furthermore, Roybal teaches the use of cytokine-producing synNotch cells to prime the endogenous immune response (page 11, final paragraph).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 39 and 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Roybal (Roybal KT et al. Cell. 2016 Oct 6;167(2):419-432.e16), as applied to claims 38 and 40, above. The rejection of claims 41-42 is further evidenced by Tang (Tang H et al. Cancer Lett. 2016 Jan 1;370(1):85-90).
Regarding claims 38 and 40, a discussion of Roybal is given above.
Regarding claim 39, Roybal teaches the method of claim 38, whereby the cell of claim 1 is administered to an individual, where furthermore the effects of which are to increase the proliferation and/or activity of a target immune cell (see rejection of claims 38 and 40, above). Furthermore, Roybal also teaches that:
“[a]n immediate application of synNotch circuits could be to improve existing T cell therapies. synNotch receptors can act as an additional environmental sensing system for TCR and CAR T cell therapies and help to modulate the activity of the cells to improve their effectiveness and safety profile. We have demonstrated that synNotch receptors can be used to control expression of directly cytotoxic factors (CARs, BiTEs). But, in addition, an important use of synNotch receptors could be the control the local production of immune stimulatory factors, such as IL-12 or other innate immune adjuvants, in TIL or engineered T cell therapies. This type of local delivery and enhancement may be particularly important, given, that factors like IL-12 are potent at driving anti-tumor immunity, but are too toxic for systemic administration. The inability of many of the current T cell therapies to infiltrate and eliminate solid tumors could be greatly improved by utilizing synNotch receptors to help the T cells to prime the local disease environment to make it more susceptible to both the cellular therapeutic and the endogenous immune response,” (page 11, final paragraph)
Thus, Roybal also teaches applying their methodological designs to improve the effects of cellular immune therapies, to include tumor infiltrating lymphocytes (“TIL,” above). Furthermore, Roybal supplies a direct motivation to do so because they teach that applying their synNotch circuits to produce cytokines such as IL-12 would improve cellular therapeutic approaches (page 11, final paragraph). Furthermore, Roybal has reduced to practice the introduction of their synNotch cells which express a cytokine, in vivo, and shown that the cell circuits and their cytokine proliferation are functional and therefore predictable (Figure 6, and throughout).
Roybal, while teaching that the target immune cell can be a TIL does not reduce such suggestion to practice.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the teachings of Roybal to target immune cells such as TILs because Roybal teaches this directly and suggests doing so, in order to improve the outcomes of immune cell therapy approaches by using such cytokine-producing synNotch cells that they teach (page 11, final paragraph). Furthermore, the results are predictable because Roybal has already reduced to practice synNotch cells, shown that they can effectively target tumor cells and can produce activating/proliferation-inducing cytokines (e.g., Figure 6 and throughout). The results are predictable because the recited method would use the components of Roybal in the same manner as Roybal.
Regarding claims 41 and 42, as discussed above, Roybal teaches using synNotch cells which produce cytokines in order to improve the outcomes of cellular therapeutics by priming the tumor environment for an improved immune response (page 11, final paragraph). Here, Roybal references Tang with regards to immune cell therapeutics. Tang teaches CAR T cells as exogenous immune cells. Thus, by referencing Tang, Roybal inherently teaches exogenous immune cells that are genetically modified and introduced into an individual, to include an exogenous CAR.
Roybal, while teaching the application of synNotch cells to improve tumor targeting by priming the tumor environment for an effective immune response by targeting exogenous immune cells such as CARs, does not explicitly reduce this method to practice.
It would have been obvious to a person of ordinary skill in the art before the time of the effective filing date of the claimed invention to modify the immune cell target of Roybal to include an exogenous immune cell target such as a CAR because Roybal directly teaches and suggests doing this, and further teaches that such an application and approach would show great improvements to immune cell therapies using exogenous immune cells. The practitioner would therefore be motivated to follow the teachings of Roybal. Furthermore, given that the synNotch cells and their cytokine producing effects were already reduced to practice by Roybal, the results are predictable.
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 38-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 10,590,182 B2 (‘182) in view of Roybal (Roybal KT et al. Cell. 2016 Oct 6;167(2):419-432.e16). The rejection is further evidenced by Tang (Tang H et al. Cancer Lett. 2016 Jan 1;370(1):85-90) and Osinalde (Osinalde N et al. Mol Cell Proteomics. 2016 Jun;15(6):2076-92).
Regarding claims 38-42, claims 1-2 of ‘182 recite:
1. A method of locally modulating an activity of a cell, the method comprising: expressing in the cell a synthetic Notch receptor comprising, in N-terminal to C-terminal order: an extracellular domain comprising a first member of a specific binding pair that is heterologous to the Notch receptor; a Notch receptor regulatory region comprising Lin-12 Notch repeats A-C, heterodimerization domains HD-N and HD-C, a binding-induced proteolytic cleavage site, and a transmembrane domain; and an intracellular domain heterologous to the Notch receptor; and contacting the cell with a second member of the specific binding pair, wherein binding of the first member of the specific binding pair to the second member of the specific binding pair induces cleavage of the binding-induced proteolytic cleavage site to activate the intracellular domain, thereby producing an activated intracellular domain, wherein the activated intracellular domain modulates an activity of the cell selected from the group consisting of: expression of a gene product of the cell, proliferation of the cell, apoptosis of the cell, non-apoptotic death of the cell, differentiation of the cell, dedifferentiation of the cell, migration of the cell, secretion of a molecule from the cell and cellular adhesion of the cell.
2. The method of claim 1, wherein the gene product of the cell is an endogenous gene product selected from the group consisting of: a chemokine, a chemokine receptor, a cytokine, a cytokine receptor, a differentiation factor, a growth factor, a growth factor receptor, a hormone, a metabolic enzyme, a proliferation inducer, a receptor, a small molecule 2.sup.nd messenger synthesis enzyme, a T cell receptor, a transcription activator, a transcription repressor, a transcriptional activator, a transcriptional repressor, a translation regulator, a translational activator, a translational repressor, an activating immunoreceptor, an apoptosis inhibitor, an apoptosis inducer, an immunoactivator, an immunoinhibitor and an inhibiting immunoreceptor.
Thus, claims 1-2 of ‘182 recite the cell of claim 1 and a method of modulating activity of a cell where the gene product can be a cytokine. Thus, ‘182 recites the same cell presently recited, where the prior art teaches the administration of said cell to an individual for various beneficial effects (see below)
‘182 does not recite that the cell is administered to an individual (claim 38), that the target cell is a TIL (claim 39), an endogenous immune cell (claim 40), or exogenous immune cell such as a CAR (claims 41-42).
Regarding claim 38, Roybal teaches the cell of claim 1 which is recited in claim 38 (SynNotch cells programmed to control the expression of a cytokine, Abstract, page 5 paragraphs 3-4 to page 6 first two paragraphs). Roybal teaches administering such cells to a mouse (an “individual” as defined by the specification at paragraph 41, Figure 6 of Roybal and page 9 final paragraphs to page 10 first paragraph). Roybal teaches a motivation to administer the cells to an individual, so as to prime a tumor microenvironment for a better immune response for either endogenous immune cells or cell therapy cells such as CAR cells as evidenced by Tang (page 11, final paragraph of Roybal as evidenced by Roybal’s reference to Tang, Tang page 4 paragraphs 1-3).
Regarding claim 39, Roybal teaches the method of claim 38, whereby the cell of claim 1 is administered to an individual, where furthermore the effects of which are to increase the proliferation and/or activity of a target immune cell (see rejection of claims 38 and 40, above). Furthermore, Roybal also teaches that:
“[a]n immediate application of synNotch circuits could be to improve existing T cell therapies. synNotch receptors can act as an additional environmental sensing system for TCR and CAR T cell therapies and help to modulate the activity of the cells to improve their effectiveness and safety profile. We have demonstrated that synNotch receptors can be used to control expression of directly cytotoxic factors (CARs, BiTEs). But, in addition, an important use of synNotch receptors could be the control the local production of immune stimulatory factors, such as IL-12 or other innate immune adjuvants, in TIL or engineered T cell therapies. This type of local delivery and enhancement may be particularly important, given, that factors like IL-12 are potent at driving anti-tumor immunity, but are too toxic for systemic administration. The inability of many of the current T cell therapies to infiltrate and eliminate solid tumors could be greatly improved by utilizing synNotch receptors to help the T cells to prime the local disease environment to make it more susceptible to both the cellular therapeutic and the endogenous immune response,” (page 11, final paragraph)
Thus, Roybal also teaches applying their methodological designs to improve the effects of cellular immune therapies, to include tumor infiltrating lymphocytes (“TIL,” above). Furthermore, Roybal supplies a direct motivation to do so because they teach that applying their synNotch circuits to produce cytokines such as IL-12 would improve cellular therapeutic approaches (page 11, final paragraph). Furthermore, Roybal has reduced to practice the introduction of their synNotch cells which express a cytokine, in vivo, and shown that the cell circuits and their cytokine proliferation are functional and therefore predictable (Figure 6, and throughout).
Regarding claim 40, as discussed above, Roybal anticipates the method of claim 38, to include the production of the cytokine IL-2 (see rejection of claim 38, above). Furthermore, as IL-2 promotes the proliferation of endogenous immune cells as evidenced by Osinalde (Abstract, page 2085, left column, second paragraph), the method taught by Roybal inherently includes the claim limitation wherein the target immune cell is an endogenous immune cell because the method of Roybal includes the induced expression of the T-cell proliferating IL-2 cytokine (rejection of claim 38, above). Furthermore, Roybal teaches the use of cytokine-producing synNotch cells to prime the endogenous immune response (page 11, final paragraph).
Regarding claims 41 and 42, as discussed above, Roybal teaches using synNotch cells which produce cytokines in order to improve the outcomes of cellular therapeutics by priming the tumor environment for an improved immune response (page 11, final paragraph). Here, Roybal references Tang with regards to immune cell therapeutics. Tang teaches CAR T cells as exogenous immune cells (page 4, paragraphs 1-3 of Tang). Thus, by referencing Tang, Roybal inherently teaches exogenous immune cells that are genetically modified and introduced into an individual, to include an exogenous CAR.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the cells recited in claims 1-2 of ‘182 to the methods rendered obvious and taught by Roybal because Roybal provides a direct motivational teaching and suggestion to do so, in order to improve therapeutic outcomes and prime a tumor environment using cytokine-expressing synNotch cells, the same cells recited in ‘182.
Claims 38-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 10,822,387 B2 (‘387) in view of Roybal (Roybal KT et al. Cell. 2016 Oct 6;167(2):419-432.e16). The rejection is further evidenced by Tang (Tang H et al. Cancer Lett. 2016 Jan 1;370(1):85-90) and Osinalde (Osinalde N et al. Mol Cell Proteomics. 2016 Jun;15(6):2076-92).
The following double patenting rejection is made using the same rationale as that applied to the rejection of the claims in combination with patent ‘182 (above), where the patent ‘387 recites the same cells presently recited in the claims (i.e., a synNotch cell producing a cytokine, which is also taught by Roybal). For the sake of brevity, the above arguments and teachings concerning Roybal, as evidenced by Tang and Osinalde, are not repeated but incorporated herein from the ‘182 rejection (above).
Regarding claim 38, claims 1 and 4 of ‘387 recite:
A method of treating a subject for a cancer, the method comprising: administering to the subject: i) a nucleic acid encoding a chimeric Notch receptor polypeptide comprising: (a) an extracellular domain that comprises an antigen binding region of an antibody, (b) a Notch core regulatory region, and (c) an intracellular domain that comprises a DNA binding domain, wherein the intracellular domain does not comprise an immunoreceptor activation domain or a co-stimulatory domain and wherein binding of the antigen binding region of the antibody to an antigen on a cancer cell induces proteolytic cleavage of the Notch core regulatory region to release the intracellular domain; and ii) a transcriptional control element that is bound by the released intracellular domain and is operably linked to a nucleic acid sequence encoding one or more cancer immunotherapy agents, wherein the released intracellular domain induces expression of the one or more cancer immunotherapy agents, thereby treating the subject for the cancer.
The method according to claim 1, wherein the one or more cancer immunotherapy agents comprises one or more surface expressed gene products, one or more secreted gene products or a combination thereof.
The method according to claim 2, wherein the one or more secreted gene products are selected from the group consisting of: an antibody, a cytokine, a chemokine, a hormone and combinations thereof.
Claims 1-4 therefore recite the cells of instantly recited claim 1, as well as a method of administering said cells to an individual. These claims therefore anticipate the presently recited claim 38.
Regarding claims 39-42, as mentioned above, the teachings of Roybal as discussed in the rejection based on patent ‘182 are incorporated herein. Thus, the combination of Roybal with patent ‘387 render obvious claims 39-42 and are predictable because Roybal and ‘387 teach the same cells (i.e., SynNotch cells programmed to secrete cytokines, see above rejection based on patent ‘182).
Claims 38-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 10,836,808 B2 (‘808) in view of Roybal (Roybal KT et al. Cell. 2016 Oct 6;167(2):419-432.e16). The rejection is further evidenced by Tang (Tang H et al. Cancer Lett. 2016 Jan 1;370(1):85-90) and Osinalde (Osinalde N et al. Mol Cell Proteomics. 2016 Jun;15(6):2076-92).
The following double patenting rejection is made using the same rationale as that applied to the rejection of the claims in combination with patent ‘182 (above), where the patent ‘808 recites the same cells presently recited in the claims (i.e., a synNotch cell producing a cytokine, which is also taught by Roybal). For the sake of brevity, the above arguments and teachings concerning Roybal, as evidenced by Tang and Osinalde, are not repeated but incorporated herein from the ‘182 rejection (above).
Regarding claim 38, claims 1 and 10 of ‘808 recite:
1 A molecular circuit comprising: (a) a nucleic acid encoding a chimeric Notch receptor polypeptide comprising: (i) an extracellular binding domain that comprises an antigen binding region of an antibody; (ii) a Notch receptor regulatory domain; and (iii) an intracellular domain that comprises a DNA binding domain, wherein the intracellular domain does not comprise an immunoreceptor activation domain or a co-stimulatory domain; wherein binding of the antigen binding region of (a)(i) to an antigen induces proteolytic cleavage of the Notch receptor regulatory domain of (a)(ii) and releases the DNA binding domain-of (a)(iii); and (b) an expression cassette comprising a transcriptional control element operably linked to a nucleic acid encoding a therapeutic agent, wherein the released DNA binding domain binds to the transcriptional control element and induces expression of the nucleic acid encoding the therapeutic agent.
10 The molecular circuit according to claim 1, wherein the therapeutic agent is selected from the group consisting of: an antibody, a chemokine, a chemokine receptor, a cytokine, a cytokine receptor, a chimeric antigen receptor (CAR), a T cell receptor (TCR), an activating immunoreceptor, an inhibiting immunoreceptor, an immunoactivator, an immunoinhibitor, an apoptosis inducer, an apoptosis inhibitor, a toxin derived protein and a site-specific nuclease.
Thus, as the circuit is encoded in a nucleic acid, a practitioner could immediately envision such circuit in a cell. Thus, claims 1 and 10 of ‘808 anticipate the cells presently recited in claims 1 and 38 of the instant application.
Regarding claims 38-42, Roybal teaches the cells rendered obvious by ‘808, as well as motivations and methods of their use and application as discussed in the rejection based on patent ‘182 above and incorporated herein. The presently recited claims are therefore obvious in view of the combination of ‘808 and Roybal, as both teach the same cells, where Roybal further renders obvious claims 38-42 (see rejection based on patent ‘182 for detailed teachings of Roybal as they relate to the claims, the teachings of which are incorporated herein).
Claims 38-42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/708,921(‘921) in view of Roybal (Roybal KT et al. Cell. 2016 Oct 6;167(2):419-432.e16). The rejection is further evidenced by Tang (Tang H et al. Cancer Lett. 2016 Jan 1;370(1):85-90) and Osinalde (Osinalde N et al. Mol Cell Proteomics. 2016 Jun;15(6):2076-92).
The following double patenting rejection is made using the same rationale as that applied to the rejection of the claims in combination with patent ‘182 (above), where the patent application ‘921 recites the same cells presently recited in the claims (i.e., a synNotch cell producing a cytokine, which is also taught by Roybal). For the sake of brevity, the above arguments and teachings concerning Roybal, as evidenced by Tang and Osinalde, are not repeated but incorporated herein from the ‘182 rejection (above).
Regarding claim 38, claims 1 and 5-6 of ‘921 recite:
1. An engineered immune cell comprising the following components: (a) a nucleic acid encoding an immune receptor that is activated by binding to a cancer-associated antigen in a solid tumor; (b) a binding triggered transcriptional switch (BTTS) that is independently activated by either a tissue- or a cancer-associated antigen in the solid tumor; and (c) a nucleic acid encoding a pro-inflammatory protein, wherein: binding of the immune receptor to the cancer-associated antigen activates the immune cell; and binding of the BTTS to its antigen activates expression of the pro-inflammatory protein and, optionally, the immune receptor if the immune receptor is not constitutively expressed in the cell.
5. The engineered immune cell of claim 1, wherein the pro-inflammatory protein is a pro-inflammatory cytokine.
6. The engineered immune cell of claim 1, wherein the pro-inflammatory protein is a cytokine selected from IL-2, IL-12, IL-15, IL-7, CD40L, or a non-natural variant of IL-2, an orthogonal cytokine, IL-12, IL-15, IL-7, CD40L that has pro-inflammatory activity, an immune checkpoint inhibitor, a decoy resistant IL-18, a dominant negative TGF-β, a dominant negative TGFb receptor, or a TGFb inhibitor/agonist.
Claim 18 recites administering the cell of claim 1 to an individual.
Thus, claims 1, 5-6, and 18 anticipate instant method claim 38 by reciting the same cell and the administration of the cell to an induvial (claim 18 of ‘921).
Regarding claims 38-42, Roybal teaches the cells rendered obvious by ‘921, as well as motivations and methods of their use and application as discussed in the rejection based on patent ‘182 above and incorporated herein. The presently recited claims are therefore obvious in view of the combination of ‘921 and Roybal, as both teach the same cells, where Roybal further renders obvious claims 38-42 (see rejection based on patent ‘182 for detailed teachings of Roybal as they relate to the claims, the teachings of which are incorporated herein).
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS CHARLES RYAN whose telephone number is (571)272-8406. The examiner can normally be reached M-F 8AM - 5PM.
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/D.C.R./Examiner, Art Unit 1635
/KIMBERLY CHONG/Primary Examiner, Art Unit 1636