DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The claim listing filed June 1, 2026 is pending.
Claims 3, 6, 8, 12-14, 18, 23, and 29 are canceled.
Claims 1, 2, 4, 5, 7, 9-11, 15-17, 19-22, and 24-28 are pending.
Claims 1, 15, and 21 are independent claims.
Election/Restriction
The Applicant’s election without traverse to Group IV (claims 21, 22, and 24-27, drawn to a method of depleting engineered T cells in a subject in need of T cell depletion); and the species of CD47 as the anti-phagocytic signaling protein and cytokine release syndrome (CRS) as the type of toxicity in the reply filed on June 1, 2026 is acknowledged.
Claims 1, 2, 4, 5, 7, 9-11, 15-17, 19, and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 21, 22, and 24-27 are currently under consideration.
Claim Rejections - 35 USC § 112
Indefinite language
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.
Claims 21, 22, and 24-27 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.
Claim 21 recites “an agent that inhibits the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells” in lines 3 and 4. The recitation of “one or more anti-phagocytic signaling proteins” being inhibited lacks antecedent basis because the prior recitation “an agent” means that there is only anti-phagocytic signaling protein being inhibited. The recitation of a singular agent followed by plural anti-phagocytic signaling proteins renders the claim indefinite because a skilled artisan would expect that the agent would only be capable of binding one anti-phagocytic signaling protein
Amending claim 21 to recite “an agent that inhibits the activity of an anti-phagocytic signaling protein expressed by the engineered T cells” would obviate this part of the rejection.
Written Description
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 that 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 that 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.
Claims 21, 22, and 24-27 are 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. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to a method of depleting engineered T cells in a subject in need of T cell depletion, which method comprises administering to a subject who has received engineered T cells an agent that inhibits the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells.
The Applicant has disclosed that any suitable agent that inhibits the activity of one or more anti-phagocytic signaling proteins may be administered to a subject who has received engineered T cells (e.g. see [0078]). The agent may be a small molecule or an antibody. The antibody may be a monoclonal antibody that specifically binds to CD47, CD42, and CD31, such as an anti-CD47 monoclonal antibody. Exemplary anti-CD47 monoclonal antibodies include, but are not limited to, Hu5F9-G4 (Liu et al., PLoSOne; 10(9): e0137345 (2015)), AO-176 (Puro et al.,Mol Cancer Ther, 19(3) 835-846 (2020); DOI: 10.1158/1535 7163.MCT-19-1079), and commercially available antibodies (e.g., Cat. No. 127519, BioLegend, Inc., San Diego, CA) (e.g. see [0078]).
The Applicant has only disclosed methods of depleting engineered T cells with an anti-CD47 antibody (e.g. see [0107] – [0111]). The anti-CD47 antibody was specifically B6.H12 (e.g. see Figure 1D).
When given the broadest reasonable interpretation in light of specification, the agent of the instant invention is defined broadly to be any agent that that inhibits the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells.
It is noted that the claims do not recite sufficient structure for the genera of agents that inhibit the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells.
In view of the Applicant’s species election, dependent claim 22 limits the one or more anti-phagocytic signaling proteins to CD47.
Dependent claim 24 limits the agent to an antibody.
Dependent claim 25 limits the agent to an anti-CD47 monoclonal antibody.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, January 5, 2001, see especially page 1106 column 3). In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted:
“A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.”
Regarding the claims that are drawn to a subgenera of agents that inhibit the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells, wherein the agents are antibodies, artisans are well aware that knowledge of a given antigen (for instance an anti-phagocytic signaling protein or specifically CD47) provides no information concerning the sequence/structure of antibodies that bind the given antigen. For example, Edwards et al. (J. Mol. Biol., 2003, 334:103-118) teach that over 1,000 different antibodies to a single protein can be generated, all with different sequences spanning almost the entire heavy and light chain germline repertoire (42/49 functional heavy chain germlines and 33 of 70 V-lambda and V-kappa light chain germlines, and with extensive diversity in the HCDR3 region sequences (that are generated by VDJ germline segment recombination) as well, see entire document).
As such, it does not seem possible to predict the sequence/structure of an antibody that binds a given antigen, as there does not appear to be any common or core structure present within all antigen binding molecules that gives rise to the function of antigen binding. Further, given data, such as that of Edwards et al., indicating the diversity of sequences in a population of antibodies that bind to a given antigen, no number of species appears to reasonably representative of the breadth of the genus of antibodies or antigen binding molecules that bind the given antigen.
It should be pointed out that it is well established in the art that the formation of an intact antigen-binding site requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three different complementarity determining regions, CDR1, 2 and 3, which provide the majority of the contact residues for the binding of the antigen binding molecule to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (Janeway Jr et al., Immunology, 3rd Edition, 1997 Garland Publishing Inc., pages 3:1-3:11.see entire selection).
Thus, based upon the prior art, skilled artisans would reasonably understand that it is the structure of the CDRs within an antibody which gives rise to the functional property of antigen binding, the epitope to that which said CDRs bind is an inherent property which appears to necessarily be present due to conservation of critical structural elements, namely the CDR sequences themselves.
This applies to the instant invention which is drawn to a subgenera of agents that inhibit the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells, wherein the agents are antibodies.
Regarding the subgenera of agents that inhibit the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells which are not antibodies, namely those that comprise small molecules, the same logic applies. Small molecules that inhibit the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells still require very precise structure in order confer binding function.
As noted above, the Applicant has disclosed that the agent of the instant invention can be any suitable agent that inhibits the activity of one or more anti-phagocytic signaling proteins. This includes small molecules and antibodies. The Applicant also discloses that the antibody may be a monoclonal antibody that specifically binds to CD47, CD42, and CD31, such as an anti-CD47 monoclonal antibody. The only agents that the Applicant has disclosed which have sufficient structure are the anti-CD47 monoclonal antibodies Hu5F9-G4, AO-176, and B6.H12. Such a disclosure does not serve to provide sufficient written description of the claimed to genera of agents that inhibit the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells. The disclosure does not identify sufficient structural features or combination of features which give rise to the function of inhibiting the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells. Additionally, there does not appear to be any reasonable shared structure present in the genera of agents which gives rise to their functional activity. Ultimately, identifying an agent on the basis of inhibiting the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells rather than by identifying the sequence/structure of the agent in question is generally insufficient to provide written description.
Therefore, in view of the breadth of the claims and the limited disclosure, artisans would reasonably conclude that applicant was not in possession of the full breadth of agents that inhibit the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells as encompassed by the claims at the time the instant application was filed.
Amending the claims to recite specific agents, which have already been disclosed by the Applicant, that inhibit the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells, such as antibodies comprising the CDR amino acid sequences of Hu5F9-G4, AO-176, and B6.H12 would obviate this part of the rejection.
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 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.
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 21, 22, and 24-27 are rejected under 35 U.S.C. 103 as being unpatentable over Maute et al. 2018 (US20180251558A1, an IDS reference filed 06/12/2024) in view of Bonifant et al. 2016 (Molecular Therapy-Oncolytics. 3, 16011, 1-7) and Reinhold et al. 1997 (J. Exp. Med. 185(1), 1-11).
Independent claim 21 is drawn to method of depleting engineered T cells in a subject in need of T cell depletion, which method comprises administering to a subject who has received engineered T cells an agent that inhibits the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells.
In view of the Applicant’s species election, dependent claim 22 limits the one or more anti-phagocytic signaling proteins to CD47.
Dependent claim 24 limits the agent to an antibody.
Dependent claim 25 limits the agent to an anti-CD47 monoclonal antibody.
Dependent claim 26 limits the engineered T cells to those which express a CAR polypeptide.
Dependent claim limits the engineered T cells to those which induce toxicity in the subject.
In view of the Applicant’s species election, dependent claim 28 limits the toxicity to cytokine release syndrome (CRS).
Maute et al. teach a method for inducing phagocytosis of a target cell by administering an anti-CD47/SIRPA agent (e.g. see [0008]). Maute et al. teach also teach that cells that express CD47, a “don't eat me” signal, evade phagocytosis (e.g. see [0004]). Anti-CD47/SIRPA agents that block the interaction between CD47 on one cell (e.g., a target cell) and SIRPA on another cell (e.g., a phagocytic cell) facilitate the phagocytosis of the target cell (e.g. see [0005]). CD47 blocking antibodies simultaneously disrupt the CD47/SIRPA interaction and opsonize target cells to which they bind, powerfully promoting macrophage phagocytosis. Anti-CD47/SIRPA agents can be used to treat and/or protect against a wide variety of conditions/disorders (e.g. see [0005]).
Regarding claims 24 and 25, Maute et al. teach that the anti-CD47/SIRPA agent is the anti-CD47 antibody Hu5F9-G4, a monoclonal antibody (e.g. see [0019] and instant [0078]).
Maute et al. do not teach that the target cells are engineered T cells or that the subject is in need of T cell depletion.
Bonifant et al. teach that CAR T cells have the capacity to elicit expected and unexpected toxicities including: cytokine release syndrome, neurologic toxicity, “on target/off tumor” recognition, and anaphylaxis (e.g. see Abstract). Abrogating toxicity has become a critical step in the successful application of this emerging technology (e.g. see Abstract).
Bonifant et al. also teach that one of the most prevalent adverse effect following infusion of CAR T cells is the onset of immune activation, known as CRS (e.g. see paragraph spanning pages 1 and 2). Management of toxicities like CRS has become an integral step in the successful clinical application of CAR T cells (e.g. see page 4, paragraph spanning left and right columns). Several methods have been proposed to ameliorate toxicity, including selective depletion of modified cells (e.g. see page 4, paragraph spanning left and right columns).
Reinhold et al. teach that CD47 is expressed on peripheral T lymphocytes (e.g. see page 2, left column, second paragraph). Reinhold et al. also teach that CD47 is a costimulator in T cell activation in both human and mouse T cells (e.g. see page 2, left column, fourth paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Maute et al. to incorporate the teachings of Bonifant et al. to include that the target cells are engineered T cells or that the subject is in need of T cell depletion. This is because strategies to abrogate CAR-T cell-induced toxicities are critical (Bonifant et al.).
Given that CAR T cells have the capacity to elicit toxicities, including CRS, the management of which has become an integral step in the successful clinical application of CAR T cells (Bonifant et al.), methods to ameliorate toxicity include selective depletion of modified cells (Bonifant et al.), T cells are known to express CD47 which acts a costimulator of T cell activation (Reinhold et al.), and blocking CD47 induced macrophage phagocytosis (Maute et al.); it would have been obvious to one of ordinary skill in the art to specifically apply the method of inducing phagocytosis of a target cell by administering an anti-CD47/SIRPA agent as taught by Maute et al. to a CAR T cell which has known toxicity.
In view of the prior art, a skilled artisan would have readily recognized that there is a need to ameliorate CAR T cell-induced toxicity, which may include depletion of the modified T cells if the toxicity is severe enough. This depletion of the severely toxic CAR T cells may be mediated through the blocking of the “don't eat me” signal CD47, which is known to be expressed on peripheral T cells, to allow for phagocytic elimination of the CAR T cells with a reasonable expectation of success.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 21, 22, and 24-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 11-13 of U.S. Patent No. 10,316,094 (the ‘094 Patent) in view of Maute et al. 2018 (US20180251558A1, an IDS reference filed 06/12/2024), Bonifant et al. 2016 (Molecular Therapy-Oncolytics. 3, 16011, 1-7), and Reinhold et al. 1997 (J. Exp. Med. 185(1), 1-11).
The instant claims are drawn to a method of depleting engineered T cells in a subject in need of T cell depletion, which method comprises administering to a subject who has received engineered T cells an agent that inhibits the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells.
The claims in the ‘094 Patent are drawn to a composition for increasing phagocytosis of a target cell, the composition comprising an antibody that binds to the target cell and thereby opsonizes the target cell; and a method of inducing phagocytosis of a target cell.
The claims in the ‘094 Patent differ from the instant invention by failing to recite that the target cell is an engineered T cell or that the antibody specifically binds to an anti-phagocytic signaling protein on the engineered T cell.
The teachings of Maute et al., Bonifant et al., and Reinhold et al. are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the claims in the ‘094 Patent and to incorporate the teachings of Maute et al., Bonifant et al., and Reinhold et al. to include the target cell is an engineered T cell and that the antibody specifically binds to an anti-phagocytic signaling protein on the engineered T cell. This is because strategies to abrogate CAR-T cell-induced toxicities are critical (Bonifant et al.), T cells are known to express CD47, an anti-phagocytic signaling protein, which acts a costimulator of T cell activation (Reinhold et al.), and blocking CD47 induces macrophage phagocytosis (Maute et al.).
Given that CAR T cells have the capacity to elicit toxicities, including CRS, the management of which has become an integral step in the successful clinical application of CAR T cells (Bonifant et al.), methods to ameliorate toxicity include selective depletion of modified cells (Bonifant et al.), T cells are known to express CD47 which acts a costimulator of T cell activation (Reinhold et al.), and blocking CD47 induces macrophage phagocytosis (Maute et al.); it would be obvious to one of ordinary skill in the art to modify the claims in the ‘094 Application to include the target cell is an engineered T cell and that the antibody specifically binds to an anti-phagocytic signaling protein on the engineered T cell with a reasonable expectation of success.
In view of the prior art, a skilled artisan would readily recognize that there is a need to ameliorate CAR T cell-induced toxicity, which may include depletion of the modified T cells if the toxicity is severe enough. This depletion of the severely toxic CAR T cells may be mediated through the blocking of the “don't eat me” signal CD47, which is known to be expressed on peripheral T cells, to allow for phagocytic elimination of the CAR T cells with a reasonable expectation of success.
Therefore, the claims in the ‘094 Patent would render the instant claims obvious.
Claims 21, 22, and 24-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 and 33-58 of U.S. Patent No. 10,889,649 (the ‘694 Patent) in view of Maute et al. 2018 (US20180251558A1, an IDS reference filed 06/12/2024), Bonifant et al. 2016 (Molecular Therapy-Oncolytics. 3, 16011, 1-7), and Reinhold et al. 1997 (J. Exp. Med. 185(1), 1-11).
The instant claims are drawn to a method of depleting engineered T cells in a subject in need of T cell depletion, which method comprises administering to a subject who has received engineered T cells an agent that inhibits the activity of one or more anti-phagocytic signaling proteins expressed by the engineered T cells.
The claims in the ‘649 Patent are drawn to a composition for increasing phagocytosis of a target cell, the composition comprising at least one of: (i) an agent that opsonizes the target cell, and (ii) an anti-CD47/single regulatory protein alpha (SIRPA) agent; and a method of inducing phagocytosis of a target cell.
The claims in the ‘649 Patent differ from the instant invention by failing to recite that the target cell is an engineered T cell or that the antibody specifically binds to an anti-phagocytic signaling protein on the engineered T cell.
The teachings of Maute et al., Bonifant et al., and Reinhold et al. are outlined in the 103 rejection above.
It would be obvious to one of ordinary skill in the art to modify the claims in the ‘649 Patent and to incorporate the teachings of Maute et al., Bonifant et al., and Reinhold et al. to include the target cell is an engineered T cell and that the antibody specifically binds to an anti-phagocytic signaling protein on the engineered T cell. This is because strategies to abrogate CAR-T cell-induced toxicities are critical (Bonifant et al.), T cells are known to express CD47, an anti-phagocytic signaling protein, which acts a costimulator of T cell activation (Reinhold et al.), and blocking CD47 induces macrophage phagocytosis (Maute et al.).
Given that CAR T cells have the capacity to elicit toxicities, including CRS, the management of which has become an integral step in the successful clinical application of CAR T cells (Bonifant et al.), methods to ameliorate toxicity include selective depletion of modified cells (Bonifant et al.), T cells are known to express CD47 which acts a costimulator of T cell activation (Reinhold et al.), and blocking CD47 induces macrophage phagocytosis (Maute et al.); it would be obvious to one of ordinary skill in the art to modify the claims in the ‘649 Application to include the target cell is an engineered T cell and that the antibody specifically binds to an anti-phagocytic signaling protein on the engineered T cell with a reasonable expectation of success.
In view of the prior art, a skilled artisan would readily recognize that there is a need to ameliorate CAR T cell-induced toxicity, which may include depletion of the modified T cells if the toxicity is severe enough. This depletion of the severely toxic CAR T cells may be mediated through the blocking of the “don't eat me” signal CD47, which is known to be expressed on peripheral T cells, to allow for phagocytic elimination of the CAR T cells with a reasonable expectation of success.
Therefore, the claims in the ‘649 Patent would render the instant claims obvious.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Grace H. Lunde whose telephone number is (703)756-1851. The examiner can normally be reached Monday - Thursday 6:00 a.m. - 3:00 p.m. (EST).
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/GRACE H LUNDE/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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