DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of invention Group I (claims 1-14,drawn to a method for treating a solid tumor in a patient in need thereof, the method comprising: administering to the patient a pharmaceutically effective amount of an anti-BTLA antibody or antigen binding fragment thereof,) in the reply filed on 1/13/2026 is acknowledged.
3. Claims 15-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/13/2026. The amendments filed 01/13/2026 are acknowledged. Claims 15-20 are withdrawn. Claims 9 and 14 are amended. Claims 1-14 are pending and under examination.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted 02 May 2024 and the references cited therein have been considered, unless indicated otherwise.
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.
5. Claims 1 and 3-14 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.
Claim 1 and 3-14 are drawn to a method for treating a solid tumor in a patient in need thereof, the method comprising: administering to the patient a pharmaceutically effective amount of an anti-BTLA antibody or antigen binding fragment thereof, wherein the solid tumor expresses herpes virus entry mediator (HVEM), and wherein at least about 1%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of tumor cells are positive for HVEM and CD8, wherein the treatment with the anti-BTLA antibody or antigen binding fragment thereof is used as an adjuvant therapy, wherein the patient receives at least one, two, three or four prior lines of therapy, wherein the pharmaceutically effective amount of the anti-BTLA antibody or antigen binding fragment thereof is administered to the patient in combination with a pharmaceutically effective amount of one or more chemotherapy drugs, wherein the anti-BTLA antibody or antigen binding fragment thereof is administered as an intravenous infusion, wherein the anti-BTLA antibody or antigen binding fragment thereof comprises one or more properties selected from the following: A) completely blocking the binding of BTLA to HVEM; B) cross- reacting with cynomolgus monkey BTLA; C) binding to human BTLA with a KD< 0.28 nM; and D) having no ability to mediate Antibody-Dependent Cellular Cytotoxicity (ADCC) effect, wherein the anti-BTLA antibody or antigen binding fragment thereof comprises a light chain variable region of LCDR1 having the amino acid sequence of SEQ ID NO: 1, LCDR2 having the amino acid sequence of SEQ ID NO: 2, LCDR3 having the amino acid sequence of SEQ ID NO: 3; and further comprises a heavy chain variable region of HCDR1 having the amino acid sequence of SEQ ID NO: 4, HCDR2 having the amino acid sequence of SEQ ID NO: 5, HCDR3 having the amino acid sequence of SEQ ID NO: 6, wherein the anti-BTLA antibody or antigen binding fragment thereof comprises a light chain variable region sequence of SEQ ID NO: 7 and a heavy chain variable region sequence of SEQ ID NO: 8, wherein the anti-BTLA antibody or antigen binding fragment thereof comprises a light chain sequence of SEQ ID NO: 9 and a heavy chain sequence of SEQ ID NO: 10, wherein the anti-BTLA antibody or antigen binding fragment thereof is in a composition comprising the effective amount of anti-BTLA antibody or antigen binding fragment thereof and a solubilizer and a stabilizer in a solution, wherein the method further comprises administering to the patient an effective amount of an anti-PD-1 or anti-PD- L1 antibody or antigen binding fragment thereof.
The specification teaches that the antibody and antigen fragments of the invention are useful to promote T cell activation and thus anti-tumor response in treating human malignancies and solid tumors including lymphoma (See page 1). The specification teaches that conditions or disorders to be treated include solid tumors (e.g., Gastrointestinal: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), large bowel (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma) colorectal; B-cell lymphoma, T-cell lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, hairy cell lymphoma, mantle cell lymphoma, myeloma, and Burkett’s lymphoma; and other tumors, including melanoma, skin (non-melanoma) cancer, mesothelioma (cells), seminoma, teratocarcinoma, osteosarcoma, xenoderoma pigmentosum, keratoacanthoma, thyroid follicular cancer and Kaposi’s sarcoma, colorectal cancer, melanoma, head and neck cancers, sarcomas, and non-Hodgkin’s lymphoma, and head and neck squamous cell cancer (See page 30). The specification teach the antibody that binds to BTLA and partially, substantially or completely blocks the binding of BTLA to HVEM.
A method for treating a solid tumor in a patient in need thereof, the method comprising: administering to the patient a pharmaceutically effective amount of an anti- BTLA antibody or antigen binding fragment thereof does not meet the written description provision of 35 U.S.C. 112, first paragraph. The claims broadly encompass treating all cancers using the aforementioned method. The specification teaches that the anti-BTLA antibody promotes T cell activation and thus anti-tumor response in treating human malignancies and solid tumors including lymphoma and is able to block the binding of BTLA to HVEM; however, this is not deemed to be predicative of treating all solid tumors using the claimed antibody. The claims broadly encompass the use of anti-BTLA antibody to treat all solid tumors; however, the specification does not demonstrate that the antibody has the function of treating any solid tumor. Therefore, the antibody has no correlation with its function. The specification is not deemed sufficient to reasonably convey to one skilled in the art that the inventors, at the time the invention was made, had possession of a method of treating all solid tumors with anti-BTLA antibody because the genus encompasses conditions which differ from those disclosed in etiologies, molecular mechanisms, diagnostic approaches, treatment modalities, and therapeutic endpoints. Furthermore, the recited genus encompasses conditions yet to be discovered and/or characterized; therefore, the skilled artisan cannot envision preventing all the contemplated diseases encompassed by the instant claims. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
A "representative number of species" means that the species, which are adequately described, are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]. "See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) "[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
The state of the art regarding the use of EGFR antibodies to treat cancer is discussed by Jonker et al. (New England Journal of Medicine. 2007; 357:2040-8). Jonker et al. disclose cetuximab, an IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR) (See page 2040). Jonker et al. teach that cetuximab treatment is associated with a significant improvement in overall survival and in progression-free survival in patients with colorectal cancer (See page 2040). The state of the art regarding the use of EGFR antibodies to treat head and neck cancer is discussed by Vermorken et al. (New England Journal of Medicine. 359:1116-27). Vermorken et al. teach that cetuximab plus platinum-fluorouracil chemotherapy improved overall survival when given as a first line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (See page 1116).
Regarding the vast genus of tumors encompassed by the claims, While the state of the art is relatively high with regard to the treatment of specific cancer types, the state of the art with regards to treating all cancers with a single treatment is underdeveloped. In particular, there is no known anticancer agent that is effective against all cancer cell types. The cancer treatment art involves a very high level of unpredictability. Heppner et al. (Cancer Metastasis Review 2:5-23; 1983) discuss the heterogeneity of tumors from different tissues, as well as the same tissue. A key point made by Heppner et al. is that tumor heterogeneity contributes greatly to the sensitivity of tumors to drugs. Heppner et al. teach that as a tumor progresses to a metastatic phenotype, the susceptibility to a particular treatment can differ, and as such, makes predicting the responsiveness to treatment difficult. Additionally, Bally et al. (US Patent No. 5,595,756) stated, "Despite enormous investments of financial and human resources, no cure exists for a variety of diseases. For example, cancer remains one of the major causes of death. A number of bioactive agents have been found, to varying degrees, to be effective against tumor cells. However, the clinical use of such antitumor agents has been highly compromised because of treatment limiting toxicities (See column 1). Sporn et al. (Chemoprevention of Cancer, Carcinogenesis, Vol. 21 (2000), 525-530) teaches the magnitude of mortality of cancers and that mortalities are in fact still rising and that new approaches to a variety of different cancer are critically needed. Sporn et al. also teach that “given the genotype and phenotype heterogeneity of advanced malignant lesions as they occur in individual patients, one wonders just exactly what are the specific molecular and cellular targets for the putative cure.”
Furthermore, the art indicates the difficulties in going from in vitro to in vivo for drug development for treatment of cancers. Auerbach et al. (Cancer and Metastasis Reviews, 2000, 19: 167-172) indicate that one of the major problems in angiogenesis research has been the difficulty of finding suitable methods for assessing the angiogenic response. For example, the 96 well rapid screening assay for cytokinesis was developed in order to permit screening of hybridoma supernatants…In vitro tests in general have been limited by the availability of suitable sources for endothelial cells, while in vivo assays have proven difficult to quantitate, limited in feasibility, and the test sites are not typical of the in vivo reality (see p. 167, left column, 1st paragraph). Gura T (Science, 1997, 278(5340): 1041-1042) indicates that “the fundamental problem in drug discovery for cancer is that the model systems are not predictive at all” (see p. 1, 2nd paragraph). Furthermore, Gura T indicates that the results of xenograft screening turned out to be not much better than those obtained with the original models, mainly because the xenograft rumors don’t behave like naturally occurring tumors in humans—they don’t spread to other tissues, for example (see p. 2, 4th paragraph). Further, when patient’s tumor cells in Petri dishes or culture flasks and monitor the cells’ responses to various anticancer treatments, they don’t work because the cells simply fail to divide in culture, and the results cannot tell a researcher how anticancer drugs will act in the body (see p. 3, 7th paragraph). Furthermore, Jain RK (Scientific American, July 1994,58-65) indicates that the existing pharmacopoeia has not markedly reduced the number of deaths caused by the most common solid tumors in adults, among them cancers of the lung, breast, colon, rectum, prostate and brain (see p. 58, left most column, 1st paragraph). Further, Jain RK indicates that to eradicate tumors, the therapeutic agents must then disperse throughout the growths in concentrations high enough to eliminate every deadly cells…solid cancers frequently impose formidable barriers to such dispersion (see p. 58, bottom of the left most column continuing onto the top of the middle column). Jain RK indicates that there are 3 critical tasks that drugs must do to attack malignant cells in a tumor: 1) it has to make its way into a microscopic blood vessel lying near malignant cells in the tumor, 2) exit from the vessel into the surrounding matrix, and 3) migrate through the matrix to the cells. Unfortunately, tumors often develop in ways that hinder each of these steps (see p. 58, bottom of right most column). Thus, the art recognizes that going from in vitro studies to in vivo studies for cancer drug developments are difficult to achieve.
Hait (Nature Reviews/Drug Discovery, 2010, 9, pages 253-254) states that “The past three decades have seen spectacular advances in our understanding of the molecular and cellular biology of cancer. However, with a few notable exceptions, such as the treatment of chronic myeloid leukemia with imatinib, these advances have so far not been translated into major increases in long-term survival for many cancers. Furthermore, data suggest that the overall success rate for oncology products in clinical development is -10%, and the cost of bringing a new drug to market is over US$1 billion.” (see page 253, left column, the 1st paragraph). Hait further teaches “The anticancer drug discovery process often begins with a promising target; however, there are several reasons why the eventual outcome for a particular cancer target may be disappointing. For example, the role of the target in the pathogenesis of specific human malignancies may be incompletely understood, leading to disappointing results”, “First, many targets lie within signal transduction pathways that are altered in cancer, but, owing to the complex nature of these pathways, upstream or downstream components may make modulating the target of little or no value”; “Second, target overexpression is often overrated. There are some instances in which overexpression predicts response to treatment.”; and “Another confounding factor is that cancer is more than a disease of cancer cells, as alterations in somatic or germline genomes, or both, create susceptibilities to transformational changes in cells and in the microenvironment that ultimately cooperate to form a malignant tissue. The putative role of cancer stem cells in limiting the efficacy of cancer therapeutics is also an area of intense interest. Therefore, effective treatments may require understanding and disrupting the dependencies among the multiple cellular components of malignant tissues. Single nucleotide polymorphisms in genes responsible for drug metabolism can further complicate the picture by affecting drug pharmacokinetics; for example, as with the topoisomerase inhibitor irinotecan.”, for example, page 253, Section “Understanding the target in context”. Hait also teaches “Drug effects in preclinical cancer models often do not predict clinical results, as traditional subcutaneous xenografting of human cancer cell lines onto immunocompromised mice produces ‘tumours’ that fail to recapitulate key aspects of human malignancies such as invasion and metastasis. Several improvements have been made, including orthotopic implantation and use of mice with humanized hematopoietic and immune systems. Newer genetic mouse models can also allow analyses of tumor progression from in situ through locally advanced and, in certain cases, widespread metastatic disease. However, whether or not these models will more accurately predict drug activity against human cancer remains to be determined. Other alternatives, including three-dimensional tissue culture or xenografts of fresh human biopsy specimens onto immunocompromised mice, have the potential advantage of including the human microenvironment. However, these approaches have yet to prove their value relative to their cost.”, for example, page 253, Section “Predictive models”. Furthermore, Hait teaches that “It is now widely thought that biomarkers will drive a personalized approach to cancer drug development. The aim is that they will cut costs, decrease time to approval, and limit the number of patients who are exposed to potential toxicities without a reasonable chance of benefit — as exemplified by the development of imatinib and trastuzumab. However, recent attempts at repeating these successes in other cancer types have been less successful.”, for example, page 254, Section “Stratified/personalized medicine”. The challenges facing cancer drug development are further confirmed and discussed in Gravanis et al (Chin Clin Oncol, 2014, 3, pages 1 -5). Gravanis et al teach “The generic mechanism of action for cytotoxics made the prediction of which tumor types might respond to them very difficult, if not impossible, and necessitated a ‘trial and error’ approach against many different types of tumors.” and “The most prominent change in oncology drug development in the last 20 years has been the shift from classic cytotoxics to drugs that affect signaling pathways implicated in cancer, which belong to the so called ‘targeted therapies’.”, for example, page 1, Section “From cytotoxics to targeted therapies: how far are we from truly personalized medicine?”. Gravanis et al. further teach “Although constantly progressing, an understanding of cancer biology is far from complete. The ability to develop new compounds or generate biological data predictive of the clinical situation relies on good quality basic research data, although the complexity and constantly evolving biology of the tumor may be to blame for the frequent non-reproducibility of research results. Systemic biology approaches of the -omic type still generate largely incomprehensible, mostly due to their volume, analytical data, few pieces of which are currently actionable/drug-g-able. Finally, animal models of cancer are similarly unable to predict the clinical situation (for example, page 3, right column, the 2nd paragraph).
Beans (PNAS 2018; 115(50): 12539-12543) teaches that across cancer types, 90% of cancer deaths are caused not by the primary tumor but by metastasis. Beans teaches that although some drugs may shrink metastases along with primary tumors, no existing drugs treat or prevent metastasis directly (See page 12540). Beans states “Without a targeted approach, metastatic tumors often reemerge. “We shrink them, we send them back to their residual state, and they reenact those survival functions and retention of regenerative powers that made them metastasis-initiating cells in the first place” (See page 12540). Beans teaches that one of the major scientific challenges of studying metastatic disease is that different forms of cancer seem to metastasize through different mechanisms and the same form of cancer may metastasize differently in different subsets of patients (See page 12542). Of note, Beans states “It’s unlikely that one researcher is going to find one pathway that proves to be the key to metastasis” (See page 12542). Bean also teaches that translating many findings into therapies also presents unique hurdles in that it is difficult to measure the effectiveness of the therapy. Secondary tumors are often minuscule, and therefore, measuring success by tumor shrinkage may not work. Measuring the incidence of metastasis after treatment is also more difficult (See page 12542).
Given Bally et al teaching of treatment-limiting toxicities in clinical use; Sporn's teaching that the cancer progression is heterogeneous as it progresses, both in genotype and phenotype; Auerbach et al teaching that one of the major problems in angiogenesis research has been the difficulty of finding suitable methods for assessing the angiogenic response; Gura's teaching that the models are unpredictable; Jain's teaching that the existing pharmacopoeia has not markedly reduced the number of deaths caused by the most common solid tumors in adults, among them cancers of the lung, breast, colon, rectum, prostate and brain; both Hait and Gravanis et al teaching various challenges facing cancer drug development, such as an understanding of cancer biology is far from complete, drug effects in preclinical cancer models often do not predict clinical results and many others; and Beans teachings that the field is highly underdeveloped with regards to preventing and treating cancer metastasis; the cited references demonstrate that the treatment of cancer is highly unpredictable, if even possible for many cancers.
The prior art does not teach anti-BTLA antibody, and therefore, it is unclear if the antibody would have the claimed function. Accordingly, one of skill in the art would conclude that the claimed invention encompasses a broad genus of cancers that may not respond to treatment with anti-BTLA antibody. Based on the teaching of the instant specification and the prior art one of skill in the art would not conclude that Applicant was in possession of the claimed method of treating the genus of solid tumor.
Consequently, the method for treating all solid tumors comprising administering anti-BTLA antibody, does not meet the written description provision of 5 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The applicant has not disclosed any species representative of the genus, which is highly variant. Applicant is reminded that Vas- Cath makes clear that the written description provision of 5 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is severable from its enablement provision. (See page 1115).
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.
7. Claims 1-9, and 13-14 are rejected under 35 U.S.C 102(a)(1) and 102(a)(2) as being unpatentable over Mataraza, et al. (U.S. Patent No: 10155813 B2, issued 12/18/2018.)
Mataraza, et al. teach a method of treating cancer in a subject comprising administering an effective amount of an antibody, or antigen binding fragment, wherein the antibody, or antigen binding fragment, specifically binds human BTLA (claim 1). Mataraza, et al. further teach the cancer is selected from a group consisting of melanoma (solid tumor), prostate cancer, pancreatic adenocarcinoma, breast cancer, colon cancer, lung cancer, squamous cell carcinoma of the head and neck (solid tumor), liver cancer, ovarian cancer, cervical cancer, thyroid cancer, glioblastoma, glioma, leukemia, lymphoma (solid tumor), and neoplastic malignancies (2). Instant claim 1 and 2 teaches a method for treating a solid tumor in a patient in need thereof, the method comprising: administering to the patient a pharmaceutically effective amount of an anti- BTLA antibody or antigen binding fragment thereof wherein the solid tumor is one or more tumors selected from the group consisting of melanoma, colorectal cancer (CRC), sarcoma, neuroendocrine tumor (NET), squamous cell carcinoma (SCC) of the parotid gland, head and neck squamous cell carcinomas (HNSCCs), follicular lymphoma, Hodgkin's lymphoma, and diffuse large B cell lymphoma (DLBCL). Instant claim 1 and 2 is anticipated by
Regarding Instant claims 3 and 4 that recite “ wherein the solid tumor expresses herpes virus entry mediator (HVEM), and wherein at least about 1%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of tumor cells are positive for HVEM”, “wherein the solid tumor co-expresses HVEM and CD8, and wherein at least about 1%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% of tumor cells are positive for HVEM and CD8”, such structures would be inherent properties of anti-BTLA antibodies, because Mataraza, et al. teach the disease or condition is mediated by an increased level of BTLA, and/or HVEM and is treated or prevented by decreasing BTLA-HVEM ligand binding, activity, or expression and further teach that blocking BTLA-HVEM ligation during priming of naïve CD8+ T cells contributes to enhanced T cell proliferation. Therefore, in order for Mataraza, et al. to decrease the BTLA-HVEM ligand binding activity and prime the CD8+ T cells, the solid tumor must express HVEM and CD8 at least 1%.
Mataraza, et al. teach anti-BTLA antibodies of the invention can be administered before, after or concurrently with one or other more therapeutic agents, e.g., a cytotoxic agent, a radiotoxic agent, or an immunosuppressive agent (paragraph 333). Mataraza further teach antibody or antibody fragments of the invention can be used alone or in combination with standard cancer treatments (for example, chemotherapy, radiotherapy or surgery) (paragraph 322). Surgery is a primary treatment, and Mataraza, et al. teach that anti-BTLA antibody can be administered after surgery as a secondary treatment also known as adjuvant therapy. Therefore, Mataraza, et al. anticipate instant claims 5 and 6.
Mataraza, et al. teach the anti-BTLA antibody in association with one or more additional components including, but not limited to a pharmaceutically acceptable carrier and/or a chemotherapeutic agent. The binding composition and/or the chemotherapeutic agent can be formulated as a pure composition or in combination with a pharmaceutically acceptable carrier, in a pharmaceutical composition (paragraph 279). This anticipates instant claim 7 as it recites the method of claim 1, wherein the pharmaceutically effective amount of the anti-BTLA antibody or antigen binding fragment thereof is administered to the patient in combination with a pharmaceutically effective amount of one or more chemotherapy drugs.
Instant claim 8 recites the anti-BTLA antibody or antigen binding fragment thereof is administered as an intravenous infusion. Mataraza, et al. teach the mode of administration can vary, including intravenous and the can be provided by continuous infusion (paragraph 288 and 292). Instant claim 8 is anticipated by Mataraza, et al.
Instant claim 9 recite the method of claim 1, wherein the anti-BTLA antibody or antigen binding fragment thereof comprises one or more properties selected from the following: A) completely blocking the binding of BTLA to HVEM; B) cross- reacting with cynomolgus monkey BTLA; C) binding to human BTLA with a KD< 0.28 nM; and D) having no ability to mediate Antibody-Dependent Cellular Cytotoxicity (ADCC) effect. Mataraza, et al. teach antibody or antigen binding fragment thereof which binds to human BTLA, comprising one of more properties selected from the group consisting of: a) blocks binding of BTLA to HVEM; b) cross reacts with cynomolgus BTLA; and c) exhibits a KD for binding to human BTLA of at most about 4.6×10^−9 (paragraph 22). Instant claim 9 is anticipated by Mataraza, et al.
Instant claim 13 recites the method of claim 1, wherein the anti-BTLA antibody or antigen binding fragment thereof is in a composition comprising the effective amount of anti-BTLA antibody or antigen binding fragment thereof and a solubilizer and a stabilizer in a solution. Mataraza, et al. teach anti-BTLA antibodies of the present invention are diluted to an appropriate concentration in a sodium acetate solution, which is a type of stabilizer, and additional agent such as polysorbate, which is a solubilizer (paragraph 286). Thus, instant claim 13 is anticipated by Mataraza, et al.
Instant claim 14 teach anti-PD-1 or anti-PD-L1 antibody can be administered with anti-BTLA antibody or antigen fragment thereof. Mataraza, et al. teach anti-BTLA antibody can be administered with anti-PD-1 or anti-PD-L1 (paragraph 322).
Double Patenting
8. 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.
10. Claims 1-2, and 10-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, 13 and 19-21 of copending Application No. 17866867
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 1 directs to a method for treating a solid tumor in a patient in need thereof, the method comprising: administering to the patient a pharmaceutically effective amount of an anti-BTLA antibody or antigen binding fragment thereof. This is recited by claims 1, 19 and 20 of copending application ‘867 direct to a method for treating or preventing BTLA-mediated diseases, such as tumors, comprising administering to a subject or patient in need thereof a therapeutically effective amount of the pharmaceutical composition which comprises anti-BTLA antibody or an antigen binding fragment thereof.
Instant claim 2 limits the solid tumor to melanoma, colorectal cancer (CRC), sarcoma, neuroendocrine tumor (NET), squamous cell carcinoma (SCC) of the parotid gland, head and neck squamous cell carcinomas (HNSCCs), follicular lymphoma, Hodgkin's lymphoma, and diffuse large B cell lymphoma (DLBCL). Claim 21 of copending application ‘867 recites the tumors can include melanoma, Hodgkin’s disease, non-Hodgkin’s lymphoma, squamous cell carcinoma, cancer of the endocrine system, and head or neck cancer.
Instant claim 10 directs to the method of claim 1, wherein the anti-BTLA antibody or antigen binding fragment thereof comprises a light chain variable region of LCDR1 having the amino acid sequence of SEQ ID NO: 1, LCDR2 having the amino acid sequence of SEQ ID NO: 2, LCDR3 having the amino acid sequence of SEQ ID NO: 3; and further comprises a heavy chain variable region of HCDR1 having the amino acid sequence of SEQ ID NO: 4, HCDR2 having the amino acid sequence of SEQ ID NO: 5, HCDR3 having the amino acid sequence of SEQ ID NO: 6. Instant SEQ NO: 1-6 are 100% to the light chain and heavy amino acid sequence of copending application ‘867 SEQ ID NO: 11 and 12 (claim 9).
Instant SEQ ID NO: 1 is 100% identical to copending application ‘329 SEQ ID NO: 12:
Query Match 100.0%; Score 79; DB 1; Length 219;
Best Local Similarity 100.0%;
Matches 16; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KSSQSLLDSDGKTYLN 16
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Db 24 KSSQSLLDSDGKTYLN 39
Instant SEQ ID NO: 2 is 100% identical to copending application ‘329 SEQ ID NO: 12:
Query Match 100.0%; Score 31; DB 1; Length 219;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 LVSKLDS 7
|||||||
Db 55 LVSKLDS 61
Instant SEQ ID NO: 9 is 100% identical to copending application ‘329 SEQ ID NO: 12:
Query Match 100.0%; Score 59; DB 1; Length 219;
Best Local Similarity 100.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 WQGTYFPYT 9
|||||||||
Db 94 WQGTYFPYT 102
Instant SEQ ID NO: 4 is 100% identical to copending application ‘329 SEQ ID NO: 11:
Query Match 100.0%; Score 32; DB 1; Length 446;
Best Local Similarity 100.0%;
Matches 5; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HTYAH 5
|||||
Db 31 HTYAH 35
Instant SEQ ID NO: 5 is 100% identical to copending application ‘329 SEQ ID NO: 11:
Query Match 100.0%; Score 96; DB 1; Length 446;
Best Local Similarity 100.0%;
Matches 17; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RIDPANGNTKYDPKFQG 17
|||||||||||||||||
Db 50 RIDPANGNTKYDPKFQG 66
Instant SEQ ID NO: 6 is 100% identical to copending application ‘329 SEQ ID NO: 11:
Query Match 100.0%; Score 56; DB 1; Length 446;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DHYGSSLLDY 10
||||||||||
Db 99 DHYGSSLLDY 108
Instant claim 11 direct to the he method of claim 1, wherein the anti-BTLA antibody or antigen binding fragment thereof comprises a light chain variable region sequence of SEQ ID NO: 7 and a heavy chain variable region sequence of SEQ ID NO: 8. Instant SEQ ID NO: 7 and 9 are 100% identical to the light chain and heavy amino acid sequence of copending application ‘867 SEQ ID NO: 11 and 12.
Instant SEQ ID NO: 7 is 100% identical to copending application ‘329 SEQ ID NO: 12:
Query Match 100.0%; Score 591; DB 1; Length 219;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DVVMTQTPLSLSVTPGQPASISCKSSQSLLDSDGKTYLNWFQQRPGQSPRRLIYLVSKLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DVVMTQTPLSLSVTPGQPASISCKSSQSLLDSDGKTYLNWFQQRPGQSPRRLIYLVSKLD 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCWQGTYFPYTFGQGTKLEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCWQGTYFPYTFGQGTKLEIK 112
Instant SEQ ID NO: 8 is 100% identical to copending application ‘329 SEQ ID NO: 11:
Query Match 100.0%; Score 633; DB 1; Length 446;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKLSCKASGYNFKHTYAHWVRQAPGQGLEWIGRIDPANGNTKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKLSCKASGYNFKHTYAHWVRQAPGQGLEWIGRIDPANGNTKY 60
Qy 61 DPKFQGRATMTADTASNTAYLELSSLRSEDTAVYYCVADHYGSSLLDYWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DPKFQGRATMTADTASNTAYLELSSLRSEDTAVYYCVADHYGSSLLDYWGQGTLVTVSS 119
Instant claim 12 direct to the method of claim 1, wherein the anti-BTLA antibody or antigen binding fragment thereof comprises a light chain sequence of SEQ ID NO: 9 and a heavy chain sequence of SEQ ID NO: 10. Instant SEQ ID NO: 9 and 10 are 100% identical to the light chain and heavy amino acid sequence of copending application ‘867 SEQ ID NO: 11 and 12 (claim 9).
Instant SEQ ID NO: 9 is 100% identical to copending application ‘329 SEQ ID NO: 12:
Query Match 100.0%; Score 1144; Length 219;
Best Local Similarity 100.0%;
Matches 219; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DVVMTQTPLSLSVTPGQPASISCKSSQSLLDSDGKTYLNWFQQRPGQSPRRLIYLVSKLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DVVMTQTPLSLSVTPGQPASISCKSSQSLLDSDGKTYLNWFQQRPGQSPRRLIYLVSKLD 60
Qy 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCWQGTYFPYTFGQGTKLEIKRTVAAPSV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCWQGTYFPYTFGQGTKLEIKRTVAAPSV 120
Qy 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL 180
Qy 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
|||||||||||||||||||||||||||||||||||||||
Db 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
Instant SEQ ID NO: 10 is 100% identical to copending application ‘329 SEQ ID NO: 11:
Query Match 100.0%; Score 2379; Length 446;
Best Local Similarity 100.0%;
Matches 446; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKLSCKASGYNFKHTYAHWVRQAPGQGLEWIGRIDPANGNTKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKLSCKASGYNFKHTYAHWVRQAPGQGLEWIGRIDPANGNTKY 60
Qy 61 DPKFQGRATMTADTASNTAYLELSSLRSEDTAVYYCVADHYGSSLLDYWGQGTLVTVSSA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DPKFQGRATMTADTASNTAYLELSSLRSEDTAVYYCVADHYGSSLLDYWGQGTLVTVSSA 120
Qy 121 STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG 180
Qy 181 LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVF 240
Qy 241 LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR 300
Qy 301 VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN 360
Qy 361 QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN 420
Qy 421 VFSCSVMHEALHNHYTQKSLSLSLGK 446
||||||||||||||||||||||||||
Db 421 VFSCSVMHEALHNHYTQKSLSLSLGK 446
Instant claim 13 recites the anti-BTLA antibody or antigen binding fragment thereof is in a composition comprises with a solubilizer and stabilizer in a solution. Claim 1 of copending application ‘867 recites a pharmaceutical composition comprising a histidine buffer, which is a stabilizer, an anti-BTLA antibody or antigen binding fragment thereof, and polysorbate, which is a type of solubilizer.
Conclusion
11. No claims are allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Syed J Abbas whose telephone number is (571)272-0015. The examiner can normally be reached M-Th, 9:00AM-4:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached at 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SYED J ABBAS/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674