Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claims 1, 5, 19, 20, 31, 47, 48, 49, 50, and 51 are currently pending and under prosecution.
Claim Rejections - 35 USC § 112
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 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 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 1, 5, 19, 20, 31, 47, 48, 49, 50, and 51 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(s) 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. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to a method of: (i) killing carcinoma cells, (ii) preventing the recurrence of a carcinoma, and/or (iv) decreasing the tumor burden in a patient having a carcinoma, comprising administering an effective amount of a NEO-201 antibody to a patient in need thereof. Dependent claim 5 recites that the antibody mediated cytotoxicity (CDC), thereby killing carcinoma in said patient. The claims encompass a vast genus of sequence variants of an “NEO-201 antibody”. The claims do not recite the structure of the NEO-201 antibody, only the function as recited above.
The instant specification discloses only a single exemplary species of a NEO-201 antibody that comprises heavy and light chain variable region SEQ IDs NOs 28 and 29, or heavy and light chain SEQ ID NOs 38 and 39, or all six CDR SEQ ID NOs 32-37, and function as claimed. [91, 184] The specification fails to disclose any other structural sequences required of a NEO-201 antibody to possess the function of treating cancer.
Fantini et al (Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the Treatment of Human Carcinomas. Front Immunol. 2018 Jan 4;8:1899) teaches that NEO-201 is a novel humanized IgG1 monoclonal antibody and found to be reactive against human carcinoma cell lines. The art teaches that this is a novel agent that warrants clinical testing as a therapeutic agent. [see whole document] Thus, the structure activity relationship of the CDR antigen binding region that recognizes NEO-201 is not known and the binding epitopes cannot be predicted based on the antibody sequences.
Additionally, by the time of the filing of the instant application, it was well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three “complementarity determining regions” (“CDRs”) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33; (see Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1). Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4.
Antibody binding to the same antigen, or even the same epitope on that antigen, can be accomplished with an impressively wide variety of antibody structures, even when the antibodies are limited to those from a particular source (Gershoni et al., Epitope Mapping, Biodrugs 2007; 21 (3): 145-156 page 146 section 1.1). The skilled artisan therefore understood that antibodies from a variety of different sources may bind the same antigen and even mediate the same functional effects, but differ widely in the details of the structure of their antigen-binding sites, particularly in the amino acid sequence and length of VH-CDR3.
Further, it is not possible to predict the amino acid sequence when an epitope is recited, because there are many different epitope arrangements, such as linear and discontinuous epitopes that is dictated by the unique interaction between an antibody and its cognate epitope (Blythe et al., Benchmarking B cell epitope prediction: Underperformance of existing methods, Protein Science (2005), 14:246–248 pg. 246) . 3D structural analyses of antibody-epitope binding highlighting that the deficiency in the ability to predict the structural features of an antibody when the epitope is disclosed (Schreiber et al.,3D-Epitope-Explorer (3DEX): Localization of Conformational Epitopes within Three-Dimensional Structures of Proteins, Wiley Interscience, 2005 42–44, 60596, page 879).
To provide adequate written description and evidence of possession of the claimed NEO-201 antibody genus, the instant specification can structurally describe representative NEO-201 antibodies that treat a carcinoma, prevent recurrence of a carcinoma or decrease tumor burden, or describe structural features common to the members of the genus which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Although Applicants may argue that it is possible to screen for NEO-201 antibodies and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future binding proteins or antibodies yet to be discovered that may function as claimed. The NEO-201 antigen provides no information about the structure of an antibody that binds to it and treats cancer.
In this case, the only factor present in the claims is a recitation of the protein function: “treating a carcinoma, preventing recurrence of a carcinoma or decreasing tumor burden”. The instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification discloses only a single exemplary antibody that functions as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. Other than the one antibody, the specification fails to provide any structural features coupled to the claimed functional characteristics.
Given the lack of representative examples to support the full scope of the claimed NEO-201 antibody required to practice the claimed methods, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of NEO-201 antibody that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Examiner Suggestion: Amend the claims to recite the structure critical to the NEO-201 antibody function, that is, a NEO-201 antibody comprising all six heavy and light chain CDRs, or comprising both the heavy and light chain variable domain SEQ IDs 28 and 29.
Claims 1, 5, 19, 20, 31, 47, 48, 49, 50, and 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 killing carcinoma cells and decreasing the tumor burden in a patient having a carcinoma, does not reasonably provide enablement for preventing the recurrence of a carcinoma. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
BREADTH OF THE CLAIMS: The claims are drawn to a method of: (i) killing carcinoma cells, (ii) preventing the recurrence of a carcinoma, and/or (iv) decreasing the tumor burden in a patient having a carcinoma, comprising administering an effective amount of a NEO-201 antibody to a patient in need thereof.
PRESENCE OR ABSENCE OF EXAMPLES: The instant specification discloses in Example 8 that the NEO-201 antibody enhances ADCC. Example 9 demonstrates the mechanism of action in which NEO-201 enhances NK-cell dependent killing. The instant specification does not disclose any examples that the claimed antibody prevent recurrence of tumors as recited by the claims.
STATE OF THE ART: A search of relevant art, does not reveal any demonstration that the combination of an sulfonamide inhibitor and an immune checkpoint inhibitor prevents cancer. Cancer has a wide variety of causes, from environmental and/or developmental exposure to ionizing radiation and/or chemical exposure in addition to some types viral and bacterial exposure (Lichtman MA et al. The Oncologist 2017; 22(5); 542–548). Even though cancer is featured by the infinite cell proliferation, its pathogenesis is extremely complex and related to many mechanisms. In general, the hallmarks of cancer consist of ten biological capabilities during the development of cancers, namely sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, tumor-promoting inflammation, genome instability and mutation, evading immune destruction and reprogramming energy metabolism (Hanahan D et al. Cell 2011 144(5) p646-674, Figures 1 and 3). More than 100 types of cancer have been identified which are typically termed for the organs or tissues where they occur. Hanahan taught over the past decade, tumors have increasingly been recognized as organs whose complexity approaches and may even exceed that of normal healthy tissues (page 661, right column second to last paragraph). Hanahan taught many human tumors are histopathologically diverse, containing regions demarcated by various degrees of differentiation, proliferation, vascularity, inflammation, and/or invasiveness (page 662, left column, first paragraph). Szabo et al (Selecting targets for cancer prevention: where do we go from here? Nat Rev Cancer 6, 867–874; 2006) teaches the intricacies and complications of cancer prevention. Szabo teaches that in addition to efficacy and toxicity concerns of cancer drugs targeting functions, there are a number of practical issues that should be considered, including drug formulation and dosing schedule to ensure adherence, as well as the cost. Szabo also teaches that in some cases the targets selected for drug therapy may even cause harm. [Whole document]
Clinical trials aimed at proving preventative cancer activity attributable to a specific intervention are largely infeasible, due to the impossibly large number of subjects and an equally impossible long timeframe. Although cancer is a common disease, specific types of cancer are still relatively infrequent events in an otherwise healthy population. Therefore, trials with cancer incidence as endpoints would necessarily involve several thousands of subjects followed for several decades. Such logistic difficulties have precluded cancer prevention trials with cancer incidence as an endpoint in all but a selected few malignancies for treatments such as tamoxifen and finasteride (Lee KW et al. Nature Reviews Cancer 2011 11 211-218, page 211, left column last paragraph) The prior art does not demonstrate that the NEO-201 antibody does not prevent recurrence of carcinoma, rather it shows that NEO-201 is a novel antibody and further studies need to be conducted for further therapeutic efficacies.
PREDICTABILITY: The specification lacks the critical steps necessary in presenting some type of predictable response in a population of hosts deemed necessary to prevent recurrence of tumors comprising administering a NEO-201 antibody. There is no evidence in the instant application or the art that as noted in the prior that demonstrate that an antibody that treats cancer would prevent the onset of cancer in subjects as claimed. The amount of experimentation required to formulate such guidance would be enormous; one would have to demonstrate the efficacy of the combination in several models across several different types of cancers and determine the appropriate regimen (doses and frequency) for use of the combination or composition in a preventative setting. Further, one would have to conduct population analysis to identify definitive characteristics which indicate that a subject is at risk of developing any cancer to a degree that would outweigh potential adverse effects of treatment with the claimed combination or composition. Thus, considering the high level of skill in the art, the state of the art, the level of predictability, and the guidance and examples provided, the experimentation required to enable the full scope of the claimed invention would not be reasonable.
QUANTITY OF EXPERIMENTATION: Undue experimentation would be required to determine if the claimed antibody could predictably prevent cancer as claimed. MPEP 2164.01 recites that “The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976)”. The experimentation needed to practice this method is undue and unreasonable as it requires determining whether the claimed NEO-201 antibody prevents cancer. A person skilled in the art will not be able to use the invention without undue experimentation. (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988))
Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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.
Claim 5 is 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.
Regarding claims, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 5, 19, 20, 31, 47, 48, 49, 50, and 51 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jones et al (WO2018218230A1), claiming priority to May 26, 2017.
It is noted that the instant specification discloses the following:
16c3 is an example of the NEO-201 encompassed by claim 1. The sequences of 16c3 (SEQ ID Nos: 28 and 29) is disclosed on page 35 of the instant specification.
Jones teaches a method of killing carcinoma cells comprising administering an effective amount of a NEO-201 antibody to a patient in need thereof. Regarding claim 5, Jones teaches that the said patient is undergoing a different cancer therapy or that the said patient is undergoing chemotherapy, such as doxorubicin. [0314-0315] Regarding claim 20 and 48, Jones teaches that the NEO-201 antibody is humanized. [0256, 0259] Regarding claims 31 and 49-51, Jones teaches the method of treating cancer in a subject comprising administering to the subject an effective amount of a cytokine agonist, interlukein-15 superagonist (IL-15N72D), in combination with a NEO-201 antibody and an immune checkpoint inhibitor to treat colorectal, lung, pancreas, uterine, ovarian, stomach and breast cancer. ([0165, 0259, 0260, 0337, 0348]; Claims 70-71, 81, 82, 140-143, 154-156, 192, and 200-203). Regarding claims 19 and 47, Jones teaches that the NEO-201 antibody is a monoclonal antibody “16C3”. [see at least 0253-0258]
Claims 1, 20, 31, 48, 49, 50, and 51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Neuman et al (2016) (Identification of target and cytotoxicity of novel and monoclonal antibody NEO-201 in ovarian and uterine cancer subtypes, Gynecologic Oncology, Vol 141, June 2016).
Neuman teaches administering the NEO-201, humanized novel monoclonal antibody, to treat patients having uterine and ovarian cancers. Neuman teaches the tumor-specific cytotoxicity of NEO-201 alone and in combination with interleukin 2 (IL-2) stimulated human peripheral blood mononuclear cells (PBMC). (Abstract, Methods, and Conclusion)
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, 5, 19, 20, 31, 47, 48, 49, 50, and 51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,767,367. Although the claims at issue are not identical, they are not patentably distinct from each other because the U.S. Patent recites a method of killing carcinoma cells comprising administering the instantly claimed NEO-201 antibody, a cytokine agonist (IL-15), wherein said patient is a NK-depleted prior. The U.S. Patent recites that the said NEO-201 antibody: (a) comprises a human IgG1 constant domain; and/or (b) is humanized, and the cancer treated may be colon cancer, pancreatic cancer, ovarian cancer, stomach cancer, lung cancer, breast cancer, or uterine cancer.
The referenced U.S. Patent and the instant application are claiming common subject matter, as follows:
Instant Application
U.S. Patent: 11,767,367
Claim 1. A method of (i) killing carcinoma cells, (ii) treating a carcinoma, (iii) preventing the recurrence of a carcinoma, and/or (iv) decreasing the tumor burden in a patient having a carcinoma comprising administering an effective amount of a NEO-201 antibody to a patient in need thereof.
Claim 5. The method of claim 1, wherein
(i) said antibody mediates complement mediated cytotoxicity (CDC), thereby killing carcinoma cells in said patient;
(ii) said patient is natural killer (“NK”)-depleted prior to or at the time of said administering;
(iii) said patient is severely NK-depleted prior to or at the time of said administering;
(iv) prior to or at the time of said administering, determining whether said patient is NK-depleted;
(v) prior to or at the time of said administering, determining whether said patient is severely NK-depleted;
(vi) said patient has NK cell deficiency (NKD), optionally comprising CNKD (e.g., CNKD1, CNKD2), or FNKD (e.g., FNKD1);
(vii) said patient is NK-depleted or severely NK-depleted as a result of another therapy;
(viii) said patient is undergoing a different cancer therapy;
(ix) said patient is undergoing chemotherapy or radiotherapy;
(x) said patient is undergoing chemotherapy, wherein said chemotherapy comprises administration of one or more proteasome inhibitors (e.g., Bortezomib, MG132), Histone deacetylase inhibitors (e.g., valproic acid, Trichostatin A, Suberovlanilide-hydroxamic acid (SAH), Sodium butyrate), genotoxic agents (e.g., doxorubicin, melphalan, cisplatin, Ara-C, aphidicolin, mitomycin, methotrexate, etoposide), GSK inhibitors (e.g., LiCl, BIO, SB21), BET inhibitors (e.g., JQ1), HSP90 inhibitors (e.g., radicicola), 17-AAG), microtubule assembly inhibitors (e.g., vincristine, cytochalasin D, nocodazole, docetaxel), and/or immunomodulatory drugs (e.g., lenalidomide);
(xi) prior to or at the time of said administering, NK cells comprise less than 5% of the peripheral blood mononuclear cells (PBMCs) in said individual;
(xii) prior to or at the time of said administering, NK cells comprise less than 3% of the peripheral blood mononuclear cells (PBMCs) in said individual;
(xiii) prior to or at the time of said administering, less than 70% of PBMC NK cells in said patient are CD56dimCD16+ NK cells;
(xiv) prior to or at the time of said administering, less than 50% of PBMC NK cells in said patient are CD56dimCD16+ NK cells; or
(xv) any combination of (i) to (xiv).
Claim 1. A method of promoting antibody-dependent cell-mediated cytotoxicity (ADCC) or natural killer (NK) cell-mediated killing of carcinoma cells which express a CEACAM antigen bound by the NEO-201 antibody in a patient in need thereof consisting essentially of administering:
(i) a NEO-201 antibody to said patient in need thereof, wherein said NEO-201 antibody comprises a heavy chain wherein the CDR1 comprises the amino acid sequence of SEQ ID NO: 32, the CDR2 comprises the amino acid sequence of SEQ ID NO: 33, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 34; and comprises a light chain wherein the CDR1 comprises the amino acid sequence of SEQ ID NO: 35, the CDR2 comprises the amino acid sequence of SEQ ID NO: 36, and the CDR3 comprises the amino acid sequence of SEQ ID NO: 37; and
(ii) an IL-15 agonist or an IL-15 superagonist, wherein said moieties (i) and (ii) are administered separately or in combination, under conditions whereby the IL-15 agonist or the IL-15 superagonist enhances ADCC or NK cell-mediated killing of carcinoma cells by the NEO-201 antibody in said patient compared to the amount of ADCC or NK cell-mediated killing of carcinoma cells if the same dose of NEO-201 antibody is administered in the absence of said IL-15 agonist or an IL-15 superagonist; and
wherein said patient is natural killer (NK)-depleted prior to or at the time of said administering; and/or said patient is severely NK-depleted prior to or at the time of said administering.
Claim 2. The method of claim 1, further comprising, prior to or at the time of said administering, determining whether said patient is NK-depleted or is severely NK-depleted.
Claim 3. The method of claim 1, wherein (a) said patient who is NK-depleted has a NK cell deficiency (NKD), optionally comprising CNKD-, or FNKD-; (b) said patient who is NK-depleted is NK-depleted or severely NK-depleted as a result of another therapy; (c) said patient who is NK-depleted is undergoing a cancer therapy; (d) said patient who is NK-depleted is undergoing chemotherapy or radiotherapy, wherein optionally said chemotherapy comprises administration of one or more proteasome inhibitors-, Histone deacetylase inhibitors-, genotoxic agents-, GSK inhibitors-, BET inhibitors-, HSP90 inhibitors-, microtubule assembly inhibitors-, and/or immunomodulatory drugs.
19. The method of claim 1, wherein said NEO-201 antibody comprises all six of the CDR sequences contained in SEQ ID NO: 28 and SEQ ID NO: 29.
47. The method of claim 2, wherein said NEO-201 antibody comprises all six of the CDR sequences contained in SEQ ID NO: 28 and SEQ ID NO: 29.
20. The method of claim 19, wherein
(i) said NEO-201 antibody comprises a variable heavy chain sequence having at least 90% identity to SEQ ID NO: 38;
(ii) said NEO-201 antibody comprises a variable light chain sequence having at least 90% identity to SEQ ID NO: 39;
(iii) said NEO-201 antibody comprises a variable heavy chain sequence having at least 90% identity to SEQ ID NO: 38 and a variable light chain sequence having at least 90% identity to SEQ ID NO: 39;
(iv) said NEO-201 antibody comprises the variable heavy chain sequence of SEQ ID NO: 38 and the variable light chain of SEQ ID NO: 39;
(v) said NEO-201 antibody comprises a heavy chain sequence having at least 90% identity to amino acids 20-470 of SEQ ID NO: 28 and a light chain sequence having at least 90% identity to amino acids 20-233 of SEQ ID NO: 29;
(vi) said NEO-201 antibody comprises all six of the CDR sequences contained in SEQ ID NO: 28 and SEQ ID NO: 29;
(vii) said NEO-201 antibody comprises the heavy chain variable region sequence contained in SEQ ID NO: 28 and the light chain variable region sequence contained in SEQ ID NO: 29;
(viii) said NEO-201 antibody comprises a heavy chain sequence containing amino acids 20-470 of SEQ ID NO: 28 and a light chain sequence containing amino acids 20-233 of SEQ ID NO: 29;
(ix) said NEO-201 antibody comprises a human IgG1 constant domain;
(x) said NEO-201 antibody is humanized;
(xi) said NEO-201 antibody is conjugated to another moiety;
(xii) said NEO-201 antibody is conjugated to another cytotoxic moiety, label, radioactive moiety, or affinity tag; or
(xii) any combination of (i) to (xi).
Claim 5. The method of claim 1, wherein said NEO-201 antibody comprises:
a variable heavy chain sequence having at least 90% identity to SEQ ID NO: 38 and a variable light chain sequence having at least 90% identity to SEQ ID NO: 39; or
the variable heavy chain sequence of SEQ ID NO: 38 and the variable light chain of SEQ ID NO: 39.
Claim 6. The method of claim 1, wherein said NEO-201 antibody: (a) comprises a human IgG1 constant domain; and/or (b) is humanized.
31. The method of claim 1, further comprising
(i) administering to the patient an effective amount of a cytokine agonist to potentiate or stimulate killing of cells of said carcinoma;
(ii) administering to the patient interleukin-2 (IL-2), interleukin 21 (IL-21), ALT-803, IL-15 inhibitors, checkpoint inhibitors, anti-PD1, anti-PDL1, anti-CTLA-4, anti-41BB, anti-OX40, anti-Tim-3, or a combination thereof;
(iii) administering to said patient a complement-regulatory protein (CRP) antagonist to potentiate or stimulate killing of cells of said carcinoma;
(iv) administering to said patient a complement-regulatory protein (CRP) antagonist which antagonizes one or more of CD46, CD55, or CD59;
(v) administering to said patient a complement-regulatory protein (CRP) antagonist which comprises an antibody or antigen-binding fragment thereof;
(vi) administering to said patient a complement-regulatory protein (CRP) antagonist which comprises an IL-15 agonist or an IL-15 superagonist;
(vii) administering to said patient a cytokine agonist which comprises a complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor a/IgG1 Fc fusion protein;
(viii) administering to said patient a cytokine agonist which comprises ALT-803;
(ix) the method of any of (i) to (viii) which includes the administration of a cytokine agonist reduces the required effective dosage of said NEO-201 antibody compared to treatment with the NEO-201 antibody alone without said cytokine agonist;
(x) said cancer comprises colon cancer;
(xi) said cancer comprises pancreatic cancer;
(xii) said cancer comprises ovarian cancer;
(xiii) said cancer comprises stomach cancer;
(xiv) said cancer comprises lung cancer;
(xv) said cancer comprises breast cancer;
(xvi) said cancer comprises uterine cancer; and/or
(xvii) any combination of (i) to (xvi).
Claim 7. The method of claim 1, wherein (said IL-15 agonist comprises ALT-803.
Claim 8. The method of claim 1, wherein the minimum effective dosage of said NEO-201 antibody that provides for killing of carcinoma cells in the patient is reduced compared to the minimum effective dosage of the NEO-201 antibody that provides for killing of carcinoma cells in the patient in the absence of said IL-15 agonist or IL-15 superagonist.
Claim 9. The method of claim 1, wherein said cancer comprises colon cancer.
Claim 10. The method of claim 1, wherein said cancer comprises pancreatic cancer.
Claim 11. The method of claim 1, wherein said cancer comprises ovarian cancer.
Claim 12. The method of claim 1, wherein said cancer comprises stomach cancer.
Claim 13. The method of claim 1, wherein said cancer comprises lung cancer.
Claim 14. The method of claim 1, wherein said cancer comprises breast cancer.
Claim 15. The method of claim 1, wherein said cancer comprises uterine cancer.
Claim 19. The method of claim 17, wherein said IL-15 agonist or superagonist is ALT-803.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/Zachariah Lucas/Supervisory Patent Examiner, Art Unit 1600
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