DETAILED ACTION
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
If the status of the application as subject to AIA or pre-AIA is incorrect, any correction of the statutory basis (e.g., changing from AIA to pre-AIA ) for a rejection under 35 U.S.C. §§ 102 and/or 103 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.
Status of the Claims
The listing of claims filed 28 March 2024 has been examined.
New claims 30–56 are pending. Original claims 1–29 are canceled.
Priority
The instant application was filed 28 March 2024; is a national stage application of PCT/IN2022/050873, filed 30 September 2022, and claims priority to IN 202121044467, filed 30 September 2021. Applicant’s claim for foreign priority is acknowledged, and a copy of the priority document has been received.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12 June 2025 is acknowledged and has been considered.
Objections to the Specification
(i) The title of the invention is objected to because it refers to the purported merits of the invention (“Novel”).
Appropriate correction is required. For guidelines on the preparation of patent titles, see MPEP § 606 (Explaining: The word novel should not be included in the title of the invention).
(ii) The abstract of the disclosure is objected to because it recites language referring to the purported merits (“novel”), phrases that can be implied (“The present invention discloses” and “The present invention also discloses”), and legal phraseology (“comprising”).
Appropriate correction is required. For guidelines on the preparation of patent abstracts, see MPEP § 608.01(b) (Explaining: The abstract should be in narrative form and avoid legal phraseology (e.g., means, said), terms referring to the purported merits of the invention (e.g., new, novel), and phrases that can be implied (e.g., The disclosure concerns, The disclosure defined by this invention). The language should be clear and concise, and not repeat information given in the title. It should not compare the invention with the prior art. The abstract is generally limited to a single paragraph within the range of 50 to 150 words in length.).
(iii) The drawings are objected to because various text in FIGs. 1, 4, 5, 7, 9, 15, and 16 is not legible (it is either too small and blurry or too faint in color to read).
Appropriate correction is required. For guidelines on the preparation of patent drawings, see 37 C.F.R. § 1.84(p) (Requiring: all text must be shown in the same direction as the drawing; all text must have a font size measuring at least 0.32 cm (1/8 inch) in height; text embedded in figures must be plain and legible; etc.).
Corrected drawing sheets in compliance with 37 C.F.R. § 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 C.F.R. § 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 U.S.C. § 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.
Claim 53 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 53 recites, “configured for administering at a dose range of . . .” Claim 53 depends from claim 50, which depends from claim 30; and claim 30 requires two compounds (5-HTR2B antagonistic compound and immunomodulatory compound). Because claim 30 refers to dose in the singular, it is unclear whether the claim is referring to the 5-HTR2B antagonistic compound or the immunomodulatory compound. [By contrast, each of claims 39–49 refers to the dose of a single compound.]
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112
The following is a quotation of 35 U.S.C. § 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 30–56 are rejected under 35 U.S.C. § 112(a) as failing to comply with the written description requirement. The claims contain subject matter that was not described in the Specification in such a way as to reasonably convey to one of ordinary skill in the art that Applicant, at the time the application was filed, had possession of the claimed invention.
In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc), the Federal Circuit stated “the hallmark of written description is disclosure.” A specification adequately describes an invention when it “reasonably conveys to those skilled in the art the inventor had possession of the claimed subject matter as of the filing date.” (Id.). “A ‘mere wish or plan’ for obtaining the claimed invention is not adequate written description.” Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1348 (Fed. Cir. 2011).
What is required to meet the written description requirement “varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). In Ariad, the Federal Circuit explained what is required to meet the written description requirement:
This inquiry, as we have long held, is a question of fact. Ralston Purina, 772 F.2d at 575. Thus, we have recognized that determining whether a patent complies with the written description requirement will necessarily vary depending on the context. Capon v. Eshhar, 418 F.3d 1349, 1357–58 (Fed. Cir. 2005). Specifically, the level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Id. For generic claims, we have set forth a number of factors for evaluating the adequacy of the disclosure, including “the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue.” Id. at 1359.
(Ariad, at 1351).
The written description of a genus, such as a chemical genus, “requires a precise structure, formula, [or] chemical name” of the claimed subject matter sufficient to distinguish it from other materials. Regents of the Univ. of Cal. v. Eli Lilly & Co., 199 F.3d 1559, 1568 (Fed. Cir. 1997). The Federal Circuit commented on that case in the Ariad decision:
We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus. Id. at 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001)). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
(Ariad, at 1350).
The factors outlined in the above Federal Circuit cases are analyzed with respect to the claimed invention in turn below.
(A) The nature and scope of the claim invention in view of the specification: the invention recited in independent claim 30 is directed to a composition comprising a 5-HTR2B antagonistic compound and an immunomodulatory compound. Dependent claim 31 further requires a chemotherapeutic drug. Dependent claim 32 recites examples of a 5-HTR2B antagonistic compound, dependent claims 33–37 recite examples of an immunomodulatory compound, and dependent claims 38 and 46–49 list examples of a chemotherapeutic drug.
There are no claims that recite a specific 5-HTR2B antagonistic compound and a specific immunomodulatory compound. There are no claims that recite a specific 5-HTR2B antagonistic compound, a specific immunomodulatory compound, and a specific chemotherapeutic drug. As such, all claims are generic with respect to at least one of the required components.
The specification does not provide a definition for 5-HTR2B antagonistic compound, immunomodulatory compound, or chemotherapeutic drug. Accordingly, the broadest reasonable interpretation of each term provides that a compound having any antagonist ability (whether selective or not) to 5-HTR2B receptor, a compound having any immunological effect (whether beneficial or not), and a compound having any therapeutic effect against cancer are within the scope of the claims.
The specification discloses the same compounds as those recited in claims 32, 33–37, 38, and 46–49 (i.e., 23 5-HTR2B antagonist compounds, 27 immunomodulatory compounds, and 5 chemotherapeutic agents). (Spec., pp.14–15).
Each respective genus of compounds (5-HTR2B antagonist, immunomodulatory, and chemotherapeutic) is defined by a property inherently possessed by the member species, as opposed to structures or chemical names. Thus, the actual scope of each genus includes the compounds disclosed in the specification and any compounds not disclosed in the specification. For example, one article (Dai et al., Scientific Reports (2016), 6:25462, 11 pages, at p.2), estimates there are over 5,000 compounds possessing anti-cancer properties from a single traditional Chinese medicine database. The specification discloses only 5 anticancer compounds.
The actual scope of each respective genus is unknown and would be essentially impossible to ascertain. Without question, however, each respective genus encompasses hundreds or thousands of species, whereas only a limited subset of species are described in the instant application. As such, there is a limited and disproportionate number of species disclosed compared to the scope of each genus in the claims.
(B) The extent and content of the prior art: 5-HTR2B antagonistic compounds, immunomodulatory compounds, and chemotherapeutic drugs were described in the prior art prior to filing the instant application.
For example, US 11,034,751 (“Kahvejian”) [IDS] discloses numerous 5-HTR2B antagonistic compounds, including many that are not described in the instant specification:
HTR2B
Methysergide Maleate, Vabicaserin hydrochloride, CHEMBL2392349,
antagonists
CHEMBL3310123, CHEMBL21343, CHEMBL2392351, CHEMBL365882,
CHEMBL3601563, CHEMBL184717, CHEMBL185376, CHEMBL270177,
CHEMBL364863, CHEMBL198949, CHEMBL422931, CHEMBL2322611,
CHEMBL3099899, CHEMBL276393, CHEMBL2022867, CHEMBL216228,
CHEMBL584554, CHEMBL1368005, CHEMBL3287218, CHEMBL2426677,
CHEMBL3264204, CHEMBL3394201, CHEMBL595449, CHEMBL1922539,
CHEMBL1922538, CHEMBL469668, CHEMBL1922537, agomelatine,
aripiprazole, sarpogrelate, lisuride, tegaserod, metadoxine, RS-127,445, SDZ
SER-082, EGIS-7625, PRX-08066, SB-200,646, SB-204,741, SB-206,553,
SB-215,505, SB-228,357, LY-266,097, and LY-272,015
(Kahvejian, col. 30).
For example, Kahvejian discloses numerous immunomodulatory compounds and chemotherapeutic agents, including many that are not described in the instant specification:
A second type of therapeutic agent that can be administered in combination with a serotonin receptor inhibitor described herein is a chemotherapeutic agent (e.g., a cytotoxic agent or other chemical compound useful in the treatment of cancer). These include alkylating agents, antimetabolites, folic acid analogs, pyrimidine analogs, purine analogs and related inhibitors, vinca alkaloids, epipodopyyllotoxins, antibiotics, L-asparaginase, topoisomerase inhibitors, interferons, platinum coordination complexes, anthracenedione substituted urea, methyl hydrazine derivatives, adrenocortical suppressant, adrenocorticosteroides, progestins, estrogens, antiestrogen, androgens, antiandrogen, and gonadotropin-releasing hormone analog. Also included is 5-fluorouracil (5-FU), leucovorin (LV), irenotecan, oxaliplatin, capecitabine, paclitaxel and doxetaxel. Non-limiting examples of chemotherapeutic agents include alkylating agents such as thiotepa and cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethiylenethiophosphoramide and trimethylolomelamine; acetogenins (especially bullatacin and bullatacinone); a camptothecin (including the synthetic analogue topotecan); bryostatin; callystatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogues); cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including the synthetic analogues, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; a sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; antibiotics such as the enediyne antibiotics (e.g., calicheamicin, especially calicheamicin gammall and calicheamicin omegall; dynemicin, including dynemicin A; bisphosphonates, such as clodronate; an esperamicin; as well as neocarzinostatin chromophore and related chromoprotein enediyne antiobiotic chromophores), aclacinomysins, actinomycin, authramycin, azaserine, bleomycins, cactinomycin, carabicin, caminomycin, carzinophilin, chromomycinis, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfomithine; elliptinium acetate; an epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-ethylhydrazide; procarbazine; razoxane; rhizoxin; sizofuran; spirogermanium; tenuazonic acid; triaziquone; 2,2′,2″-trichlorotriethylamine; trichothecenes (especially T-2 toxin, verracurin A, roridin A and anguidine); urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); cyclophosphamide; thiotepa; taxoids, e.g., paclitaxel; chloranbucil; gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum coordination complexes such as cisplatin, oxaliplatin and carboplatin; vinblastine; platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine; vinorelbine; novantrone; teniposide; edatrexate; daunomycin; aminopterin; xeloda; ibandronate; irinotecan (e.g., CPT-11); topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid; capecitabine; and pharmaceutically acceptable salts, acids or derivatives of any of the above. Two or more chemotherapeutic agents can be used in a cocktail to be administered in combination with the first therapeutic agent described herein. Suitable dosing regimens of combination chemotherapies are known in the art.
Biologic Cancer Agents
Another type of therapeutic agent that can be administered in combination with a serotonin receptor inhibitor described herein is a therapeutic agent that is a biologic such a cytokine (e.g., interferon or an interleukin (e.g., IL-2)) used in cancer treatment. In other embodiments the biologic is an anti-angiogenic agent, such as an anti-VEGF agent, e.g., bevacizumab. In some embodiments the biologic is an immunoglobulin-based biologic, e.g., a monoclonal antibody (e.g., a humanized antibody, a fully human antibody, an Fc fusion protein or a functional fragment thereof) that agonizes a target to stimulate an anti-cancer response, or antagonizes an antigen important for cancer. Such agents include Rituximab; Daclizumab; Basiliximab; Palivizumab; Infliximab; Trastuzumab; Gemtuzumab ozogamicin; Alemtuzumab; Ibritumomab tiuxetan; Adalimumab; Omalizumab; Tositumomab-I-131; Efalizumab; Cetuximab; Bevacizumab; Natalizumab; Tocilizumab; Panitumumab; Ranibizumab; Eculizumab; Certolizumab pegol; Golimumab; Canakinumab; Ustekinumab; Ofatumumab; Denosumab; Motavizumab; Raxibacumab; Belimumab; Ipilimumab; Brentuximab Vedotin; Pertuzumab; Ado-trastuzumab emtansine; and Obinutuzumab. Also included are antibody-drug conjugates. Examples of biologic cancer agents that can be used in combination with serotonin receptor inhibitors described herein are shown in Table 7 below.
TABLE 7
APPROVED CANCER ANTIBODIES
Antibody
Company
Antigen
Indication
ado-trastuzumab
Genentech
HER2
Metastatic breast cancer
emtansine
alemtuzumab
Genzyme
CD52
B-cell chronic lymphocytic leukemia
atezolizumab
Genentech
PD-L1
Urothelial carcinoma
Metastatic non-small cell lung cancer
avelumab
EMD Serono
PD-L1
Metastatic Merkel cell carcinoma
bevacizumab
Genentech
VEGF
Metastatic colorectal cancer
blinatumomab
Amgen
CD19
Precursor B-cell acute lymphoblastic
leukemia
brentuximab
Seattle Genetics
CD30
Hodgkin lymphoma
vedotin
Anaplastic large-cell lymphoma
cetuximab
ImClone Systems
EGFR
Metastatic colorectal carcinoma
daratumumab
Janssen Biotech
CD38
Multiple myeloma
dinutuximab
United Therapeutics
GD2
Pediatric high-risk neuroblastoma
durvalumab
AstraZeneca
PD-L1
Urothelial carcinoma
elotuzumab
Bristol-Myers
SLAMF7
Multiple myeloma
Squibb
ibritumomab
Spectrum
CD20
Relapsed or refractory low-grade, follicular, or
tiuxetan
Pharmaceuticals
transformed B-cell non-Hodgkin's lymphoma
ipilimumab
Bristol-Myers
CTLA-4
Metastatic melanoma
Squibb
necitumumab
Eli Lilly
EGFR
Metastatic squamous non-small cell lung
carcinoma
nivolumab
Bristol-Myers
PD-1
Metastatic melanoma
Squibb
Metastatic squamous non-small cell lung
carcinoma
obinutuzumab
Genentech
CD20
Chronic lymphocytic leukemia
ofatumumab
Glaxo Grp
CD20
Chronic lymphocytic leukemia
olaratumab
Eli Lilly
PDGFRA
Soft tissue sarcoma
panitumumab
Amgen
EGFR
Metastatic colorectal cancer
pembrolizumab
Merck
PD-1
Metastatic melanoma
pertuzumab
Genentech
HER2
Metastatic breast cancer
ramucirumab
Eli Lilly
VEGFR2
Gastric cancer
rituximab
Genentech
CD20
B-cell non-Hodgkin's lymphoma
trastuzumab
Genentech
HER2
Metastatic breast cancer
Cancer-Specific Agents
In some embodiments, the therapeutic agents administered with the serotonin receptor inhibitors described herein are cancer-specific. Cancer-specific agents are agents that have been shown to be particularly effective against certain types of cancer. Cancer-specific agents that can be administered with the serotonin receptor inhibitors described herein are listed in Table 8 below.
TABLE 8
CANCER-SPECIFIC AGENTS
Cancer type
Agents
Pancreatic cancer
Chemotherapeutics (Paclitaxel Albumin-stabilized Nanoparticle Formulation,
Erlotinib Hydrochloride, Everolimus, Fluorouracil Injection, Gemcitabine
Hydrochloride, Irinotecan Hydrochloride Liposome, Mitomycin C, Sunitinib
Malate, Folfirinox, Gemcitabine-Cisplatin, Gemcitabine-Oxaliplatin, Off,
Lanreotide Acetate, Abraxane, Gemcitabine, Irinotecan, 5-FU, Oxaliplatin)
Melanoma
Checkpoint inhibitors (pembro, ipi, nivolumab, durvalumab), BRaf inhibitors
(vemurafenib, debrafenib), MEK inhibitors, CDK4 inhibitors (ribociclib)
Renal cell
Checkpoint inhibitors (pembro, ipi, nivolumab, durvalumab), mTOR inhibitors
carcinoma
(everolimus), bevacizumab
Lung cancer
Checkpoint inhibitors (pembro, ipi, nivolumab, durvalumab), EGFR inhibitors
(erlotinib, gefitinib, cetuximab)
Esophageal cancer
Chemotherapeutic agents (5FU, docetaxel), trastuzumab
Ovarian cancer
Chemotherapeutics (taxanes, cisplatin)
Uterine cancer
Chemotherapeutics (taxanes, cisplatin)
Head and Neck
Checkpoint inhibitors (pembro, ipi, nivolumab, durvalumab), EGFR inhibitors
cancer
(erlotinib, gefitinib, cetuximab)
Mesothelioma
Chemotherapeutics (pemetrexed, cisplatin)
(Id., col. 81–84).
Based on just a single reference, Kahvejian, a person having ordinary skill in the art would appreciate that the claims are directed to three large genera of compounds.
(C) The maturity of the science or technology: the specification states, “there is no conclusive evidence present in the prior art on the effect of the 5-HTR2B receptor or its antagonists and its effect on cancer [and] also no studies in the art on the effect of immunomodulators in conjunction with 5-HTR2B antagonists”:
The prior art discussed the role of antagonists of 5-HTR2B for cancer therapy. However, there is no conclusive evidence present in the prior art on the effect of the 5-HTR2B receptor or its antagonists and its effect on cancer. There are also no studies in the art on the effect of immunomodulators in conjunction with 5-HTR2B antagonists. Hence there is a need for providing a treatment using 5 HTR2B antagonists. However, since cancer treatment is very critical, it is necessary to administer a synergistic combination so as to effectively treat cancer when a subject is affected. There is no such synergistic combination involving HTR2B antagonists. Hence there is a need for such synergistic combination.
(Spec, p.2).
Based on such characterizations, the science appears to be in its infancy.
(D) The predictability of the aspect at issue: the pharmaceutical art is generally recognized as unpredictable. In re Fisher, 427 F.2d 833, 839 (CCPA 1970). The art requires each potential drug candidate to be assessed for physiological activity. (Id.). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. In this case, there is no evidence suggesting the claimed invention is more predictable than the pharmaceutical art is generally.
The question of written description
When the above factors and the evidence of record are considered as a whole, the specification does not adequately describe a representative number of species to support the generically claimed invention to a composition comprising a 5-HTR2B antagonistic compound and an immunomodulatory compound, and optionally a chemotherapeutic drug. Each respective genus includes a disproportionate number of compounds compared to the limited examples disclosed in the specification, the science is in its infancy, and the science is unpredictable. Because the specification fails to disclose a representative number of species for each genus, it would not reasonably convey to those skilled in the art the inventor had possession of the claimed subject matter as of the filing date.
Appropriate correction is required.
Examiner recommends amended the claims to recite the subject matter supported by the disclosures in the specification. For example, the subject matter of claims 32 and 34 can be added to claim 30; and the subject matter of claim 38 can be added to claim 31.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of 35 U.S.C. § 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. § 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Graham v. John Deere Co., 383 U.S. 1, 17 (1966); MPEP § 2141(II).
Claims 30–56 are rejected under 35 U.S.C. § 103 as being unpatentable over US 11,034,751 (“Kahvejian”) [IDS] in view of Sansone et al., Innov Clin Neurosci (2011), 8(11), 10–14 (“Sansone”), Yamamoto et al., Invest New Drugs (2017), 35, 207–216 (“Yamamoto”), Wu et al., World J. Gastroenterol (2004), 10(20), 3048–3052 (“Wu”), Cabanes et al., Int’l J Oncology (1998), 12, 1035–1040 (“Cabanes”), Le Pla et al., Chem. Res. Toxicol. (2007), 20, 1177–1182 (“Le Pla”), and Tung et al., The Prostate (2011), 71, 675–681 (“Tung”).
The Graham factors are addressed in turn below.
Determining the scope and contents of the prior art
Kahvejian discloses a composition comprising a serotonin receptor inhibitor, including a specific 5-HTR2B antagonistic compound, for treating cancer. (Kahvejian, 25:38–48; 27:32–41 (col:line); col. 30, Table 2). Kahvejian discloses, for example, agomelatine, aripiprazole, sarpogrelate, lisuride, tegaserod, metadoxine, and RS-127,445. (Id.).
Kahvejian discloses the serotonin receptor inhibitor can be administered at a dose sufficient to modulate an immune cell activity. (Id., 43:37–40; 43:57–60).
Kahvejian discloses a dose for the serotonin receptor inhibitor of 10mg/kg to 500 mg/kg. (Id., 140:24–28; 141:25–29).
Kahvejian discloses a combination therapy comprising a serotonin receptor inhibitor, including a specific 5-HTR2B antagonistic compound, and a second agent. (Id., col. 80–84).
Kahvejian discloses a combination therapy comprising a serotonin receptor compound and an imunomodulatory compound and/or a chemotherapeutic agent. (Id.). Kahvejian discloses numerous immunomodulatory compounds and chemotherapeutic agents. (Id., col. 81–84).
Kahvejian discloses a combination therapy comprising a serotonin receptor compound and an imunomodulatory compound such as, for example, nivolumab, pembrolizumab, ipilimumab, durvalumab, etc. (Id.).
Kahvejian discloses a combination therapy comprising a serotonin receptor compound and a chemotherapeutic agent such as, for example, 5-fluorouracil (5-FU), paclitaxel, oxaliplatin, and irinotecan. (Id.).
Kahvejian discloses a pharmaceutical composition. (Id., 130:9–133:9).
Kahvejian discloses a pharmaceutical composition for administration via intravenous, intradermal, oral, transdermal, etc. (Id.).
Kahvejian discloses a solid pharmaceutical composition, including tablets and pills. (Id.).
Kahvejian discloses a method of treating cancer of epithelial origin, including breast cancer, in a patient comprising administering a pharmaceutical composition. (Id., 1:23–7:16; 77:8–80:42; 134:19–138:2).
Sansone discloses agomelatine as 25 mg tablets. (Sansone, p.12)
Yamamoto discloses a dose of nivolumab of 1–20 mg/kg. (Yamamoto, p.207).
Wu discloses a dose of 5-FU of 20 mg/kg. (Wu, p.3048).
Cabanes discloses a dose of paclitaxel of 5 mg/kg. (Cabanes, p.1035).
Le Pla discloses a dose of oxaliplatin of 10 mg/kg. (Le Pla, p.1178).
Tung discloses a dose of irinotecan of 20 mg/kg. (Tung, p.675).
Ascertaining the differences between the prior art and the claims at issue
Kahvejian does not disclose an example of a composition having a 5-HTR2B antagonistic compound and an immunomodulatory compound.
Kahvejian does not disclose the composition weight percent ranges for the 5-HTR2B antagonistic compound (claims 39–43), the immunomodulatory compound (claim 45), or the chemotherapeutic drug (claims 46–49).
Sansone may not disclose the composition weight percent ranges for the 5-HTR2B antagonistic compound (claims 39–43).
Resolving the level of ordinary skill in the pertinent art
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
Considering objective evidence present in the application indicating obviousness or nonobviousness
The instant application asserts the combination of 5-HTR2B antagonists and anti-PD1, anti-PD-L1, and anti-CTLA4 monoclonal antibody therapy reduced tumor growth in MC38 colon cancer compared to the control (the 5-HTR2B antagonists alone) and the monoclonal antibody therapy alone. (Spec., Example 13, p.36). The data to support that assertion is in FIGs. 15A–15G. (Id.).
The question of obviousness
Based on the above factors, it would have been prima facie obvious for a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed invention based on Kahvejian because Kahvejian discloses a composition comprising a 5-HTR2B antagonistic compound for treating cancer and Kahvejian suggests a combination comprising the 5-HTR2B antagonistic compound and an immunomodulatory compound and/or a chemotherapeutic drug.
Kahvejian discloses all the limitations in the claims except for the concentrations/dosages in claims 39–43 and 46–49. Cabenes, Le Pla, Tung, Wu, and Yamamoto disclose the claimed dosages for paclitaxel, oxaliplatin, irinotecan, 5-FU, and nivolumab. One of ordinary skill in the art would have combined the teachings of the cited references because all of the drugs recited in the claims were known in the art and information regarding their concentrations and/or dosages were known and/or available to a person skilled in the art. Moreover, there is no evidence the dosage or concentration of any component is critical to the claimed invention.
Sansone discloses 25mg tablets of agomelatine but does not disclose whether the relative weight percent of the active ingredient is in the range of 5–70%. However, there is no evidence of record suggesting the adjustment of the weight percent of an active ingredient in a tablet is a critical feature of the claimed invention and/or something other than common knowledge in the manufacture of such tablets. One of ordinary skill in the art would have had a reasonable expectation of success combining the teachings of the cited references because the 5-HTR2B antagonistic compounds recited in the claims were known in the art and information regarding their concentrations and/or dosages were known or available to a person skilled in the art.
The data in the specification has been considered but does not overcome a prima facie case of obviousness. First, as noted, each of the instant claims is generic with respect to at least one required component. There are no claims reciting a specific 5-HTR2B antagonistic compound and a specific immunomodulatory compound; and no claims reciting a specific 5-HTR2B antagonistic compound, a specific immunomodulatory compound, and a specific chemotherapeutic drug. As such, any data in the specification showing a synergistic or unexpected effect for a specific combination is not commensurate in scope with the claims. Second, the drawings cannot be fully reviewed because several figures (e.g., FIGs. 15A–15G) are too small and appear blurry such that the data cannot be reviewed.
Conclusion
No claims are allowed.
Communication
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/J.M.N./Patent Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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