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 .
Applicant’s election of group III, claims 27-32 and 34-51, in the reply filed on 10/10/25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 27-32 and 34-51 are being acted upon.
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 27-32 and 34-51 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 27 and 34 (and claims dependent therefrom) are indefinite in the recitation of a particle comprising a core and an antigenic construct tightly associated to the core. As an initial matter, the term “tightly” is a relative term which renders the claim indefinite. The term “tightly” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Furthermore, the scope of what is encompassed by the recitation that the antigenic construct is tightly associated “with the core” is unclear and indefinite. The ordinary meaning of a core is a central part that is enveloped by a part of a different nature. Thus, the limitation that the antigen is tightly associated with the core of a particle would imply that there is another layer over the antigen/core. However, the specification exemplifies a particle having covalent attachment of an antigen to the surface of a paramagnetic polystyrene particle. Would the claims encompass surface attachment to a solid particle, or do the claims require attachment to a central part of a particle (i.e. a core) which comprises an outer layer over the core? Does the reference to a core merely serve to exclude hollow particles, for example? The specification does not define the term core or attachment to a core, and the scope the claims is unclear and indefinite. For the purposes of examination, the claims are being interpreted as encompassing an antigenic construct covalently attached to the surface of a solid particle.
Claim 27 is also indefinite since it is directed to a method of treating or “preventing” cancer comprising administering an antigen construct comprising a protein or peptide “expressed by a cancer cell in the subject”. The term prevention would imply the subject does not yet have cancer, and it is unclear how the method can prevent cancer but also require administering a peptide “expressed by a cancer cell in the subject”, which requires a subject with cancerous cells, i.e. a patient with cancer.
Claim 27 recites the limitation "the phagocytosis" in line 6. There is insufficient antecedent basis for this limitation in the claim, and it is suggested to amend the claim to recite “allowing for phagocytosis”. It is suggested to amend claim 34, line 26 in a similar manner.
Claim 32 is indefinite in the recitation of administering a cytokine “simultaneously, sequentially or separately”. The claim depends from claim 30, which is a method of administering a DC cancer vaccine and a dose of anti-cancer T cells. It is not clear in claim 32 wherein the simultaneous administration, for example, of the cytokine is with respect to the DC cancer vaccine, the dose of anti-cancer T cells, both, or either.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claims 27-32 and 35-51 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method for treating cancer in a subject;
does not reasonably provide enablement for:
A method for preventing cancer in a subject.
The specification disclosure is insufficient to enable one skilled in the art to practice the invention as claimed without an undue amount of experimentation. Undue experimentation must be considered in light of factors including: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill in the art, the level of predictability of the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention, in re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art.” In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling (MPEP 2164.03)” The MPEP further states that physiological activity can be considered inherently unpredictable.
The claims encompass treating or preventing cancer, however, preventing or curing cancer is extremely unpredictable due the heterogeneous nature of the disease, the difficulty in identifying at risk individuals, and the numerous challenges in effective treatment (see for example, Carey, 2010). Thus, it would be highly unpredictable as to whether a therapy could be used to prevent cancer, as is encompassed by the instant claims.
Given the unpredictability of the art and the breadth of the claims, the instant specification must provide a sufficient an enabling disclosure commensurate in scope with the instant claims. The specification provides no guidance or examples on prevention of cancer. Thus, based on the unpredictability of the art, the breadth of the claims, and the lack of guidance provided by the instant specification, it would require undue experimentation to practice the full scope of the claimed method.
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.
Claim(s) 27, 36, 42-44, 47, 49-50, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2008/019366 (of record).
WO2008/019366 teaches a method of treating cancer by eliciting an immune response to an antigen in subject in need thereof comprising contacting an APC in vitro with an antigenic preparation comprising a particle having an antigen attached to the surface, and then administering the APCs to the animal to stimulate the subjects T cells (i.e. a vaccine, see pages 9-10 and the claims, in particular). WO2008/019366 teaches that the APCs take up and phagocytose the particles (See page 3 and 12, in particular). WO2008/019366 teaches that the APC is a dendritic cell (see page 4, in particular). WO2008/019366 teaches the antigen is a cancer antigen, such as a mutant oncogenic form of p53 protein, and that the subject is one which is in need of an antigen specific immune response specific to the antigen, i.e. the p53 is expressed by the cancer cell in the subject, see abstract and pages 3-4 in particular). It is noted that p53 protein, which is hundreds of amino acids in length, would be comprised of numerous different peptide epitopes that are covalently linked to each other via peptide bonds, and would include a mutated epitope, and therefore the limitations of claims 42-43 would be inherent when using said mutated p53 protein taught in WO2008/019366. WO2008/019366 teaches solid particles such as a polymer bead, latex bead, polystyrene bead, or iron oxide particles (i.e. paramagnetic), i.e. particles with a core (see pages 12-14, in particular). WO2008/019366 teaches that the antigen is attached via covalent methods, i.e. tightly associated ( see pages 12-14, in particular). Thus, WO2008/019366 teaches solid particles, wherein an antigen is covalently attached to the surface, which meets the limitations of a particle comprising a core and an antigenic construct tightly associated to the core. WO2008/019366 teaches that the antigen is a protein cancer antigen, such a mutant oncogenic form of p53 (i.e. an antigenic construct comprising at least one peptide, and a neoantigen with a somatic mutation, see page 20-21 and the claims, in particular). WO2008/019366 teaches that the APC are provided from the treated animal, i.e. from the subject as recited in claim 36 (see paragraph 37, in particular). WO2008/019366 teaches particular size of for example, 0.3 uM, which would anticipate a size of less than 5.6 uM (see paragraph 13, in particular).
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.
Claim 27, 36-37, 41-51 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2008/019366 (of record), in view of WO2018234516 (of record).
The teachings of WO2008/019366 are described above.
The reference differs from the claimed invention in that it does not explicitly teach a paramagnetic particle having a polystyrene core with a size between 0.5 uM and 2 uM, a sterilizing wash, or multiple different tumor antigens.
WO2018234516 teaches methods of using APC such as dendritic cells, that have phagocytosed a phagocytosable particle having one or more tumor neoantigenic constructs tightly associated thereto, for activating antigen specific T cells. WO2018234516 teaches including at least three different tumor neoantigens on the particles to maximize T cell expansion and that the tumor neoantigens are expressed in a cancer cell of the subject (see pages 5, 13, 15, and 20, in particular). WO2018234516 teaches a preferred phagocytosable particle size of 0.5- 2uM in a largest diameter (See pages 10-11, in particular). WO2018234516 a preferred phagocytosable particle can be superparamagnetic with a polystyrene core (see page 11-13). WO2018234516 teaches that that particles should be treated with a sterilizing wash to remove contaminants like micro-organisms and endotoxin (See pages 11-13, in particular). WO2018234516 that the T cells and APCs are obtained from a blood sample of the subject (see page 21, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a sterilizing wash, as taught by WO2018234516, in the method of treating cancer of WO2008/019366. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because WO2018234516 teaches that that particles should be treated with a sterilizing wash to remove contaminants like micro-organisms and endotoxin. Furthermore, optimizing the particles type and size, using the parameters of WO2018234516 would be routine and well within the purview of the ordinary artisan. For example, WO2018234516 teaches that a preferred particle for loading dendritic cells to induce antigen specific T cells is paramagnetic with a polystyrene core of a size between 0.5 and 2 uM. Furthermore, the use of a blood sample for providing T cells and dendritic cells, as taught by WO2018234516, would be routine and well within the purview of the ordinary artisan.
Claim 27-32, 34-40, 42-50 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2008/019366 (of record), in view of 5,662,907 and WO2019185041.
The teachings of WO2008/019366 are described above. WO2008/019366 also teaches an embodiment for treating cancer wherein APC that have been treated in vitro for delivery of the antigenic particles can be used to directly stimulate a patients T cells with the APCs outside the body so as to expand antigen specific T cells, and then the T cells are transplanted back into the body (See paragraph 41, in particular).
The reference differs from the claimed invention in that it does not explicitly teach preparing the T cells from a subject whom has previously been administered a DC cancer vaccine or administration of both the APC and the T cells. The reference also does not explicitly teach using blood dendritic cells, a PDL1 inhibitor, multiple different tumor antigens, or treating skin cancer.
The ‘907 patent teaches peptides incorporated into dendritic cells for use as vaccines and also teaches adoptive transfer of antigen specific T cells (see columns 12-13, in particular). The ‘907 patent teaches that a combination of both vaccine administration and adoptive T cell transfer can be used to induce a strong immune response (See column 2, in particular). The ‘907 patent also teaches T cell transfer together with IL-2 to prolong survival of the T cell in vivo (i.e. simultaneously, see columns 12-13, in particular).
WO2019185041 teaches a method of treating cancer comprising administering to a subject antigen loaded dendritic cells in combination with antigen specific T cells (see pages 1-4, in particular). WO2019185041 teaches that the T cells are prepared by culturing T cells in vitro with tumor antigen loaded dendritic cells, and that both the dendritic cells and the T cells are provided from the subject to be treated (see pages 1-4). WO2019185041 also teaches that that the dendritic cells loaded with the tumor antigens can be administered prior to the T cells (See paragraph 155, in particular). WO2019185041 also teaches that repeating entire treatment method, including the T cell preparation method, after administration of the dendritic cells and T cells (See paragraph 156, in particular). WO2019185041 teaches using multiple different tumor antigens, wherein the antigens are neoantigens, including using at least three different tumor antigens, in order to improve T cell activation (i.e. different antigenic constructs comprising different peptide epitopes, see paragraph 39). WO2019185041 teaches including a checkpoint inhibitor, such as anti-PD-1 or anti-PD-L1 in the T cell dendritic cell co-cultures to enhance T cell responses, or further administering said checkpoint inhibitor (See paragraph 9-13, 98, page 54, and Fig. 5, in particular). WO2019185041 teaches treating various types of cancer including melanoma (i.e. a skin cancer, see paragraph 118, in particular). WO2019185041 teaches that dendritic cells can be provided from PMBC, i.e. from the blood (see paragraph 15, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to administer both the dendritic cells having phagocytosed the antigen particles, and the antigen specific T cells produced by culture with said dendritic cells, in the method of treating cancer of WO2008/019366, as taught by the ‘907 patent and WO2019185041. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because the ‘907 patent teaches that doing so can induce a strong immune response. Therefore, one would combine both treatment regiments (dendritic cell and T cells taught in WO2008/019366) to provide for an increased and strong immune response to better treat cancer in the subject. Regarding the timeframes recited in claim 28, it is noted that the cited references render obvious providing T cells and dendritic cells from the patient, and it would be obvious to do so to create each respective cell type to provide a treatment, which would meet the limitation of performing steps a)-c) before administering dendritic cells. However, it would also be obvious to repeat the entire treatment regimen to enhance treatment, since WO2019185041 specifically teaches that the entire treatment method, including the T cell preparation method, can be repeated after dendritic cell vaccination, thus also meeting the limitations of performing steps a)-c) after dendritic cell vaccination. Repeating the treatment, as made obvious by the cited references, would also meet the limitations of claim 30, wherein the subject has been previously administered a dose of anti-cancer T cells, and the limitations of claim 34, wherein the subject has previously been administered a DC cancer vaccine.
Furthermore, the ordinary artisan would also be motivated to culture the cells with a PD-L1 inhibitor and to administer the cells with the checkpoint inhibitor, and to use multiple different tumor antigens, as taught by WO2019185041 to enhance T cell responses and to improve T cell activation The ordinary artisan would also be motivated to further administer IL-2, as taught by the ‘907 patent to prolong survival of the T cell in vivo. Furthermore, selecting from sources of dendritic cells, such as blood dendritic cells, optimizing the particle sizes, or types of cancer that could be treated, as taught by the cited references, would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385). Regarding optimizing particle sizes, WO2008/019366 teaches a particle size range of 0.3-20 uM, and it would be obvious to use particle sizes from the lower end of the range, such as a 1 uM particle, and doing so would fall within the range recited in claim 48. Regarding claim 39, WO2008/019366 teaches experiments wherein dendritic cells are prepared for use in vitro to activate T cells, wherein they are washed before contact with the T cells (see paragraph 83, in particular). It would also be obvious to use the same washing procedure before administration of the dendritic cells in vivo, i.e. removing extracellular particles from the dendritic cells.
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 27-32 and 34-51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 51-81 of copending Application No. 18/999,139 or claims 1-21 of 19/317,328 in view of WO2008/019366, 5,662,907 and WO2019185041.
The copending applications claim a method of treating cancer in a subject comprising administering to the subject anti-tumor T cells producing by contacting a phagocytosable particle with an APC, wherein the phagocytosable particle has tumor neoantigen construct tightly associated thereto, and contacting T cells samples from the subject with the APC in vitro to expand the T cells. The copending applications claim three or more tumor neoantigen construct comprising peptides that induce T cells, i.e. epitopes, that the antigens are expressed in cancer cells of the subject, performing a sterilizing wash, and that the particles are covalently linked to the antigen and that the particles have paramagnetic properties and a size of less than 5.6 uM, and that the particles is a polymer particle, i.e. particles with a core. Although not specifically claimed, it would be obvious to further administer a dendritic cell that has phagocytosed the particles prior to the T cells to improve the immune response in the treated subject, based on the teachings of WO2008/019366, 5,662,907 and WO2019185041, for the same reasons set forth above. Furthermore, it would be obvious to repeat the treatment based on WO2019185041 for the same reasons set forth above. Furthermore, it would be obvious to wash the APCs after contact, to use dendritic cells as the APC, and to contact with a PDL1 inhibitor, and to administer IL-2, based on the teachings of WO2008/019366, 5,662,907, WO2018234516, and WO2019185041.
for the same reasons set forth above.
This is a provisional nonstatutory double patenting rejection.
Claims 27-32 and 34-51 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14, 18-19, 21-36 of copending Application No. 17/417,601, in view of WO2008/019366, 5,662,907, WO2018234516, and WO2019185041.
The ‘601 application claims a method of treating cancer in a subject comprising administering to the subject a phagocytosable particle comprising a core and a neoantigen construct tightly associated to the core, wherein the core has a largest dimension of 0.5uM to 2.5 uM, wherein the neoantigen construct comprises a peptide or protein expressed by the cancer cell in the subject, and further comprising producing anti-tumor T cells by contacting a phagocytosable particle with an APC from the subject, wherein the phagocytosable particle has tumor neoantigen construct tightly associated thereto, contacting T cells samples from the subject with the APC in vitro and administering the T cells to the subject. The copending application claims using two or more tumor neoantigen construct comprising peptides that induce T cells, that the particles have paramagnetic properties that the core comprises polystyrene. The ‘601 application claims treating breast cancer or colon cancer. The ‘601 application does not explicitly claim that the first step comprises administering a dendritic cell loaded with said particle. However, it would be obvious to do so based on the teachings of WO2008/019366, which teaches the use of particles administered directly to the subject as a vaccine, or alternatively, that they can be administered in the form of a dendritic cell that has been loaded with the particles in vitro prior to administration. Selecting from the methods of administering phagocytosable particles for inducing T cell responses would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385). . Furthermore, it would be obvious to repeat the administration regimen, as taught by WO2019185041 and the ‘907 patent, to increase the immune responses, and doing so would result in administration of the dendritic cells and anti-cancer T cells to a subject who has previously been administered a dose of anti-cancer T cells and dendritic cells. Furthermore, it would be obvious to wash the APCs after contact, to perform a sterilizing wash, to use dendritic cells as the APC, and to contact with a PDL1 inhibitor, and to further administer IL-2, based on the teachings of WO2008/019366, 5,662,907, WO2018234516, and WO2019185041 for the same reasons set forth above.
This is a provisional nonstatutory double patenting rejection.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dan Kolker, can be reached at telephone number 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644