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 .
Specification
The disclosure is objected to because of the following informalities: Please update the status of parent application U.S. Patent Application number 18/666, 594 in the first paragraph of the specification.
Appropriate correction is required.
Claim Objections
Claims 4-11, 17-18 and 23 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim shall not serve as a basis for any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claim 20 is objected for the following informality: Please remove “e” before “IL-15N72D:IL-15RαSu/Fc”.
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 1-3, 12-16 and 19-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12168048 (‘048). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘048 claims disclose:
Claims 1-3: a method of treating cancer comprising:
a) administering to a subject having cancer an effective dose of Bacillus Calmette-Guerin and an IL-15:IL-15Rα fusion protein complex (immunotherapeutic agents);
b) isolating immune effector cells from a biological sample of the subject following step a, wherein the immune effector cells comprise antigen presenting cells, CD8.sup.+ T cells, and natural killer (NK) cells;
c) culturing the immune effector cells with a composition comprising the IL-15:IL-15Rα fusion protein complex; and
d) reinfusing the cultured immune effector cells into the subject, thereby treating the cancer.
Claim 2: the IL-15:IL-15Rα fusion protein complex comprises an IL-15:IL-15RαSu/Fc complex; wherein the IL-15:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
The ‘048 claims disclose the cancer is selected from the group consisting of bladder cancer, a glioblastoma, prostate cancer, B-cell neoplasms, multiple myeloma, B-cell lymphoma, Hodgkin's lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, cutaneous T-cell lymphoma, T-cell lymphoma, urothelial/bladder carcinoma, melanoma, lung cancer, renal cell carcinoma, breast cancer, gastric cancer, esophageal cancer, head and neck cancer, colorectal cancer, ovarian cancer, non-small cell lung carcinoma, B cell non-Hodgkin lymphoma, and squamous cell head or neck carcinoma.
The ‘048 claims disclose the antigen presenting cells comprise dendritic cells (immune effector cells).
The ‘048 claims disclose further comprising culturing the immune effector cells with one or more tumor antigens, or a nucleic acid encoding one or more tumor antigens.
The ‘048 claims disclose the biological sample of the subject is a urine sample.
The ‘048 claims disclose the further comprising administering at least one therapeutic agent selected from the group consisting of radiation therapy, a chemotherapeutic agent, and a second immunotherapeutic agent.
Claim 12-16: The ‘048 claims disclose the a method of inducing an anti-bladder cancer immune response in a subject who has bladder cancer, comprising:
a) administering to the subject an effective dose of BCG and an IL-15:IL-15Rα fusion protein complex;
b) isolating immune effector cells such as dendritic cells from a biological sample of the subject following step a;
c) culturing the dendritic cells with a composition comprising the IL-15:IL-15Rα fusion protein complex; and
d) reinfusing the dendritic cells into the subject, thereby inducing an anti-bladder cancer immune response.
Claim 13: The ‘048 claims disclose wherein the IL-15:IL-15Rα fusion protein complex comprises an IL-15:IL-15RαSu/Fc complex, wherein the IL-15:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
The ‘048 claims disclose further comprising administering a chemotherapeutic agent.
The ‘048 claims disclose, further comprising culturing the immune effector cells with tumor antigens.
Claims 19-22: The ‘048 claims disclose a vaccine composition comprising the dendritic cells isolated from a urine sample of a subject with bladder cancer primed with the IL-15:IL-15Rα fusion protein complex; wherein the IL-15:IL-15Rα fusion protein complex comprises an IL-15:IL-15RαSu/Fc complex, wherein the IL-15:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
Claims 1-3, 12-16 and 19-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12016911 (‘911). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘911 claims disclose:
Claim 1: a method of treating cancer comprising:
a) administering to a subject having cancer an effective dose of Bacillus Calmette-Guerin (immunotherapeutic agent) and an IL-15:IL-15Rα fusion protein complex;
b) isolating antigen presenting cells (immune effector cells) from a biological sample of the subject following step a;
c) culturing the antigen presenting cells with a composition comprising the IL-15:IL-15Rα fusion protein complex; and
d) reinfusing the cultured antigen presenting cells into the subject, thereby treating the cancer.
Claims 2-3: The method of claim 1, wherein the IL-15:IL-15Rα fusion protein complex comprises an IL-15:IL-15RαSu/Fc complex wherein the IL-15:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
The ‘911 claims disclose the cancer comprises bladder cancer, a glioblastoma, prostate cancer, B-cell neoplasms, multiple myeloma, B-cell lymphoma, Hodgkin's lymphoma, chronic lymphocytic leukemia, acute myeloid leukemia, cutaneous T-cell lymphoma, T-cell lymphoma, urothelial/bladder carcinoma, melanoma, lung cancer, renal cell carcinoma, breast cancer, gastric cancer, esophageal cancer, head and neck cancer, colorectal cancer, ovarian cancer, non-small cell lung carcinoma, B cell non-Hodgkin lymphoma, and squamous cell head or neck carcinoma.
The ‘911 claims disclose the antigen presenting cells are dendritic cells.
The ‘911 claims disclose further comprising culturing the antigen presenting cells with tumor antigens.
The ‘911 claims disclose the biological sample of the subject is a urine sample.
The ‘911 claims disclose further comprising administering a chemotherapeutic agent.
Claim 12 and claim 15-16: The ‘911 claims disclose A method of inducing an anti- bladder cancer immune response in a subject in need thereof having bladder cancer, comprising:
a) administering to the subject an effective dose of BCG and an IL-15:IL-15Rα fusion protein complex;
b) isolating antigen presenting cells from a biological sample of the subject following step a; c) culturing the antigen presenting cells such as dendritic cells with a composition comprising the IL-15:IL-15Rα fusion protein complex; and
d) reinfusing the dendritic cells into the subject, thereby inducing an anti-bladder cancer immune response.
Claims 13-14: The ‘911 claims disclose wherein the IL-15:IL-15Rα fusion protein complex comprises an IL-15:IL-15RαSu/Fc complex, wherein the IL-15:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
The ‘911 claims disclose further comprising administering a chemotherapeutic agent.
The ‘911 claims disclose, further comprising culturing the antigen presenting dendritic cells with tumor antigens.
Claims 19-22: The ‘911 claims disclose a vaccine composition comprising the dendritic cells isolated from a urine sample of a subject with bladder cancer primed with the IL-15:IL-15Rα fusion protein complex; wherein the IL-15:IL-15Rα fusion protein complex comprises an IL-15:IL-15RαSu/Fc complex, wherein the IL-15:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
Claims 19-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11857612 (‘612). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘612 claims disclose:
a vaccine composition comprising antigen presenting cells, wherein the antigen presenting cells are dendritic cells isolated from a urine sample of a subject with bladder cancer, wherein the dendritic cells can be primed with the IL-15:IL-15Rα fusion protein complex; wherein the IL-15:IL-15Rα fusion protein complex comprises an IL-15:IL-15RαSu/Fc complex, wherein the IL-15:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
Claims 1-3 and 12-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,554,167 (‘167) in view of Naoe et al. Int J Urol. 2007;14(6):532-538.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘167 claims disclose:
Claims 1-3 and 12-16: An effective dose (a vaccine composition) of an immunotherapeutic agent made by the method comprising administering to a subject an immunotherapeutic agent (a BCG treated subject); isolating BCG primed dendritic cells from a urine sample (biological sample) of the subject; culturing the dendritic cells with a composition comprising an IL-15:IL-15Rα fusion protein complex by exposing ex vivo.
The ‘167 claims disclose the IL-15:IL-15Rα fusion protein comprises an IL-15:IL-15RαSu/Fc complex.
The ‘167 claims disclose the IL-15:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
The ‘167 claims disclose the immunotherapeutic agent comprises Bacillus Calmette-Guerin (BCG).
The ‘167 claims disclose the antigen presenting immune effector cells are dendritic cells.
The ‘167 claims disclose the biological sample of the subject is a urine.
The ‘167 claims do not disclose that the composition is administered to a subject to treat bladder cancer or administered to a subject to induce an anti-cancer immune response.
Nao et al disclose that dendritic cells pulsed with BCG result in the maturation of the dendritic cells and the number of NKT cells and γδT cells increased after culturing with BCG-pulsed dendritic cells. Nao et al disclose that BCG-pulsed DCs also activated the NKT cells and γδT cells and lymphocytes cocultured with the BCG pulsed dendritic cells showed unspecific cytotoxic activity against a bladder cancer line. See under abstract.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the invention to have reinfused the BCG primed dendritic cells exposed ex vivo IL-15:IL-15Rα fusion protein complex of the ‘167 claims to the subject of the ‘167 claims diagnosed with urothelial/bladder carcinoma cancer to treat the urothelial/bladder carcinoma in said subject or to induce an anti-bladder cancer response in said subject having the urothelial/bladder carcinoma, thus resulting in the instant invention with a reasonable expectation of success.
The motivation to do so is that Nao et al disclose that dendritic cells pulsed with BCG result in the maturation of the dendritic cells and the number of NKT cells and γδT cells increased after culturing with BCG-pulsed dendritic cells and that BCG-pulsed DCs also activated the NKT cells and γδT cells and lymphocytes cocultured with the BCG pulsed dendritic cells showed unspecific cytotoxic activity against a bladder cancer line.
Claims 19-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11554167 (‘167). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘167 claims disclose:
a vaccine composition comprising BCG primed dendritic cells isolated from a urine sample of a subject with urothelial/bladder cancer, wherein the dendritic cells are primed with the IL-15:IL-15Rα fusion protein complex; wherein the IL-15:IL-15Rα fusion protein complex comprises an IL-15:IL-15RαSu/Fc complex, wherein the IL-15:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
Claims 1-3, 12-16 and 19-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11364291 (‘291). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘291 claims disclose:
Claim 1: A method of treating urothelial/bladder carcinoma, comprising: administering to a subject having urothelial/bladder carcinoma an effective dose of an immunotherapeutic agent; and isolating an immune effector cell from a urine sample of the subject; culturing the immune effector cells with a composition comprising an IL-15:IL-15Rα fusion protein complex, reinfusing the cultured immune effector cells to the subject, thereby treating the carcinoma.
Claims 2: The method of claim 1 wherein the composition comprises an IL-15N72D:IL-15RαSu/Fc complex.
Claim 3: The method of claim 1, wherein the immunotherapeutic agent comprises Bacillus Calmette-Guerin (BCG).
The ‘291 claims disclose the immune effector cell comprises T cells, B cells, natural killer (NK) cells, natural killer T (NK-T) cells, dendritic cells, mast cells, myeloid-derived phagocytes or combinations thereof.
The ‘291 claims disclose the immune effector cell is a dendritic cell.
The ‘291 claims disclose wherein the IL-15:IL-15Rα fusion protein complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
The ‘291 claims disclose further comprising culturing the immune effector cells with urothelial/bladder carcinoma antigens.
Claims 12, 15 and 16: The ‘291 claims disclose a method of inducing an anti-bladder cancer immune response in a subject in need thereof, comprising: administering to the subject an effective dose of Bacillus Calmette-Guerin (BCG);
isolating dendritic cells from a urine sample of the subject;
culturing the dendritic cells with a composition comprising an IL-15:IL-15Rα fusion protein complex,
reinfusing the dendritic cells to the subject, thereby inducing an anti-bladder cancer immune response.
Claim 13: The method of claim 12 wherein the composition comprises an IL-15N72D:IL-15RαSu/Fc complex.
Claim 14: The method of claim 13, wherein the IL-15N72D:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
The ‘291 claims disclose further comprising administering one or more chemotherapeutic agents.
The ‘291 claims disclose further comprising culturing the dendritic cells with urothelial/bladder carcinoma antigens.
Claims 19-22: ‘the ‘291 claims disclose a vaccine composition comprising BCG primed dendritic cells isolated from a urine sample of a subject with bladder cancer who has been treated with BCG, wherein the dendritic cells are primed with the IL-15:IL-15Rα fusion protein complex; wherein the IL-15:IL-15Rα fusion protein complex comprises an IL-15:IL-15RαSu/Fc complex, wherein the IL-15:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules.
Claim Rejections - 35 USC § 112
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 1-3, 13-16 and 20 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.
• Claim 1 recites the limitation "the subject" in line 2. There is insufficient antecedent basis for this limitation in the claim because there is no previous recitation of a subject in the claim e.g. the preamble. Applicant can obviate the rejection by changing "the subject" in line 2 to "a subject".
• Claim 1 preamble recites a method of treating cancer, however, in the body of the claim it is not indicated that the subject has cancer.
• In claim 2, claim 13 and claim 20, is the “the IL-15N72D:IL-15RαSu/Fc complex” in addition to the IL-15:Il-15Rα fusion protein complex in claim 1, claim 12 and claim 19, respectively? Or Applicant means the method of claim 1, wherein the IL-15:IL-15Rα fusion protein complex is a IL-15N72D:IL-15RαSu/Fc complex?
• Claim 14 the recitation of “the IL-15N72D:IL-15RαSu/Fc complex” lacks antecedent basis in claim 12.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 15-16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 15 recites the BCG is optionally administered to the subject. Claim 16 recites that BCG is administered to the subject. However, claim 12 from which claims 15-16 depends recites administering to the subject an effective dose of BCG. Therefore, claim 15 fails to include all the limitations of claim 12 and claim 16 fails to further limit the subject matter of claim 12 because in claim 12 the BCG is administered to the subject.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Soon-Shiong et al. US2019/01171153 4-25-2019 filed 9-26-2018 in view of Wong et al. US 2018/0200366 7-19-2018.
Soon-Shiong et al disclose a method of treating cancer, comprising:
Administering to the subject an effective dose of BCG -paragraph 21 disclosing when the anti-bladder cancer therapy includes an immunotherapy, the immunotherapy is one or more of the following modalities: intravesical bacillus Calmette-Guérin (BCG)vaccine therapy, systemic immune checkpoint therapy, and NK cell therapy;
Isolating an immune effector cell from a biological sample of the subject - paragraph 22 disclosing in particular embodiments, when the immunotherapy is NK cell therapy, the NK cells are allogenic and autologous and paragraph 23 isolating NK cells from the blood of the subject;
Culturing the NK cell with a composition comprising IL-15 – see paragraph 24 disclosing expanding the isolated NK cells ex vivo in a suitable cell culture medium, and paragraph 25 disclosing collecting the autologous NK cells expanded; see paragraph 54 the NK cells are allogenic and autologous, or are activated in vitro and reinfused into the subject and paragraph 59 disclosing the autologous NK cells are activated in vitro by administering one or more NK activating cytokines, such as IL-15.
Reinfusing the cultured NK cells to the subject, thereby treating the cancer – see paragraph 26 disclosing a further step includes, for example, infusing the collected autologous NK cells back into the subject.
Soon-Shiong et al does not disclose the IL-15 is an IL-15:IL-15Ra fusion protein complex such as IL-15N72D:IL- 15RalphaSu/Fc complex.
Wong et al disclose interleukin-15 (IL-15) is an important cytokine for the development, proliferation, and activation of effector NK cells. See paragraph 110. Wong et al in paragraph 111 disclose to facilitate clinical development of an IL-15 based cancer therapeutic, an IL-15 mutant (IL-15N72D) with increased biological activity compared to IL-15 was identified. The pharmacokinetics and biological activity of this IL-15 super-agonist (IL-15N72D) was further improved by the creation of IL-15N72D:IL-15Rα/Fc fusion complex (ALT-803), such that the super agonist complex has at least 25-times the activity of the native cytokine in vivo.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have modified the method of Soon-Shiong et al by activating the NK cells with IL-15N72D:IL-15Rα/Fc fusion complex (ALT-803) corresponding to IL-15N72D:IL-15RαSu/Fc fusion complex , thus resulting in the instant invention with a reas9onable expectation of success. The motivation to do so is that Wong et al disclose that ALT-803 has increased biological activity compared to IL-15.
Claim(s) 19-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gomes-Giacoia et al. PloS ONE 9(6):e96705. doi:10.1371/journal.pone.0096705, 2014 (11 pages) as evidenced by Romee et al. Blood. 131 (23): 2515-2527, 2018 in view of Kumar et al. Biol Open. 2018 Jun 15; 7(6): bio032045 (8 pages).
Claim 19: Gomes-Giacoia et al disclose a vaccine composition comprising Bacillus Calmette-Guerin (BCG) and an IL-15:IL-15Rα fusion protein complex (ALT-803 aka N-803). See page 2 column 2 under “intravesical treatment”.
Claim 19-21: The ALT-803 comprises an IL-15N72D:IL-15RαSu/Fc complex (see page 2 column 1 2nd paragraph), wherein the IL-15N72D:IL-15RαSu/Fc complex comprises a dimeric IL-15RαSu/Fc and two IL-15N72D molecules (thus is “N-803” as evidenced as defined in the instant specification at p. 6 lines 18-22) by Romee et al. Romee et al disclose that the ALT-803 is a superagonist complex of an IL-15 mutein N72D bound to the sushi domain of IL-15Ralpha fused to the immunoglobulin G1 Fc and extends the in vivo half-life of IL-15 and mimics the physiologic trans-presentation of IL-15. Romee disclose that ALT-803 comprises a dimeric IL-15αSu/Fc and two IL-15N72D. See visual abstract in Romee.
Gomes-Giacoia et al disclose the vaccine composition is formulated in PBS (see page 2 column 1 2nd paragraph) and thus is suitable for the intended use of an administration mode selected from the group consisting of systemic, intravenous, local, subcutaneous, intramuscular, inhalation and intraperitoneal.
Gomes-Giacoia et al disclose that the vaccine composition is used for treating bladder cancer.
Gomes-Giacoia et al does not disclose the vaccine composition comprises BCG primed dendritic cells.
Kumar et al disclose that BCG is used for the treatment of bladder cancer and dendritic cells are the most potent antigen-presenting cell, play a key role in mounting T cell response against tumor cells (see under introduction) and that BCG stimulated dendritic cells have a prolonged lifespan due to enhanced survival (see abstract). Gomes et al (under the discussion) disclose that with increased life-span antigen-loaded DCs can interact with a higher proportion of cognate T cells, resulting in the heightened T cells responses.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date to have substituted the BCG in the composition of Gomes-Giacoia et al with BCG pulsed dendritic cells, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that Kumar et al disclose that dendritic cells are the most potent antigen-presenting cell, play a key role in mounting T cell response against tumor cells and that BCG stimulated dendritic cells have a prolonged lifespan due to enhanced survival and that with increased life-span antigen-loaded DCs can interact with a higher proportion of cognate T cells, resulting in the heightened T cells responses. For these reasons, the BCG stimulated dendritic cells having enhanced survival and prolonged life span and which leads to interaction with a higher proportion of cognate T cells resulting in the heightened T cell responses needed to treat bladder cancer would have been advantageous over the BCG to a person of ordinary skill in the art as of the effective filing date.
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gomes-Giacoia et al. PloS ONE 9(6):e96705. doi:10.1371/journal.pone.0096705, 2014 (11 pages) as evidenced by Romee et al. Blood. 131 (23): 2515-2527, 2018 and Kumar et al. Biol Open. 2018 Jun 15; 7(6): bio032045 (8 pages) as applied to claims 19-21 and 25-26 above, further in view of Beatty et al. BJU Int. 2004 Dec; 94(9):1377-83, 2004.
The combination of Gomes-Giacoia et al and Kumar et al does not disclose the dendritic cells are isolated from a urine sample of a subject diagnosed with urothelial/bladder carcinoma.
Beatty et al disclose that dendritic cells, antigen-presenting cells with the potential to stimulate primary T-cell responses, may appear in the urine of patients with bladder cancer.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the invention to have obtained the dendritic cells to be stimulated with BCG from urine samples of a patient with bladder cancer subject, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that Beatty et al disclose that urine of patients with bladder cancer is a source of dendritic cells. The additional rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element dendritic cells from (bone marrow derived as disclosed in Kumar et al) for dendritic cells from urine of a patient with bladder cancer for another yields predictable results i.e. antigen presentation to one of ordinary skill in the art.
See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007): simple substitution for one known element for another to obtain predictable results and some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Status of Claims
Claims 1-3, 12-16 and 19-22 are rejected. Claims 4-11, 17-18 and 23 objected to.
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/OLUWATOSIN A OGUNBIYI/
Primary Examiner, Art Unit 1645
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