DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5, 8, 10, 12 and 14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 5 recites the broad recitation “modified cellulose”, and the claim also recites “such as hydroxypropyl cellulose, carboxymethylcellulose or hydroxyethyl cellulose” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 8 recites compounds, which are unclear as to what they are: e.g. what is “calcium-sodium and potassium-phosphate”, “calcium- and sodium- phosphate”, “calcium- and potassium- phosphate”. Claim 8 is further vague and indefinite, because it seems to combine two dependent claims in itself, with the second narrower claim beginning with the language “preferably” on the last but one line.
Claim 10 is vague and indefinite, because it seems to combine two dependent claims in itself, with the second narrower claim beginning with the language “more preferably” on the last but one line.
Claim 12 is vague and indefinite, because it is unclear what the language “further comprising at least an active agent selected from a chemotherapeutic agent and an immunotherapeutic agent” means. Does that mean “further comprising at least one additional active agent selected from a chemotherapeutic agent and an immunotherapeutic agent”, since claim 1, from which claim 12 depends, already recites a combination of active chemotherapeutic agents.
Claim 14 is vague and indefinite because it does not place any limitation on the amount being administered, e.g. therapeutically effective, or synergistically effective, etc. Yet, at the same time it recites compounds, which are fairly cytotoxic, so on the high end the compounds would not be treating a cancer, but would rather be cytotoxic or lethal overall. This renders the claim vague and indefinite, because it is unclear how to practice Applicant’s claimed method.
Claim Rejections - 35 USC § 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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over US 20230372391 A1 to Canal Barnils et al. (“Canal Barnils”), further in view of Zuo et al., Inhibition of STAT3 blocks protein synthesis and tumor metastasis in osteosarcoma cells, J Exp Clin Cancer Res, 2018 Oct 4;37(1):244 (“Zuo”, of record).
Canal Barnils relates to a composition including a polymer aqueous solution, a bioceramic material and reactive oxygen and nitrogen species (RONS) and its use for the treatment of bone cancer and/or bone tissue regeneration. (Abstract). Canal Barnils discloses that when said polymer solution polymerizes and/or crosslinks, a hydrogel is formed. ([0011]). Canal Barnils discloses preparing different polymeric solutions by dissolving in water or aqueous saline solutions suitable concentrations polymers such as fibrin, fibronectin, collagen, alginate, gelatin, etc, and mixtures thereof. ([0042]). The RONS include hydrogen peroxides (H2O2), nitrites (NO2−), peroxynitrites, etc. ([0004]). The bioceramic material comprises calcium. ([0010]).
Canal Barnils further discloses that the composition further comprises an active pharmaceutical ingredient. Preferably, the active pharmaceutical ingredient is a chemotherapeutic drug or a coadjuvant in the cancer therapy. Different kinds of drugs can be incorporated/loaded to the bioceramic component of the composition or in the hydrogel component. These can include chemotherapeutic drugs (i.e. methotrexate, cisplatin, doxorubicin, ifosfamide, etoposide, bleomycin) or other therapeutics, such as monoclonal antibodies, cytokines, and specific inhibitors of different proteins related with disease progression, or other biomolecules. ([0024]).
Canal Barnish discloses a concentration of 0.68 and 200.00 mg/L H202 and 0.46 mg/L and 36.80 mg/L of nitrogen dioxide (NO2-). ([0010].
To convert to mM concentration, per Applicant’s claims, the general formula for the conversion is:
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74
402
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Greyscale
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121
581
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Converting 0.46 mg/L and 36.80 mg/L of nitrogen dioxide (NO2-):
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139
402
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Greyscale
These ranges fall within Applicant’s claimed concentration ranges.
Per Canal Barnils, the bioceramic material comprising calcium comprises calcium phosphate. In a preferred embodiment, the bioceramic material comprising calcium is other than calcium carbonate. Preferably, the bioceramic material comprising calcium is selected from tetra-calcium phosphate, dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, alpha-tricalcium phosphate, beta-tricalcium phosphate, monocalcium phosphate monohydrate, hydroxyapatite, calcium deficient hydroxyapatite, fluorapatite, amorphous calcium phosphate, calcium-sodium and potassium-phosphate, calcium- and sodium-phosphate, calcium- and potassium-phosphate, calcium pyrophosphate, calcium carbonate, calcium sulphate, calcium sulphate hemihydrate, calcium oxide and calcium hydroxide, and mixtures thereof. ([0019]).
Per Canal Barnils, a second aspect of the invention relates to the composition of the first aspect for use in the treatment of cancer. Preferably, the cancer is bone cancer, more preferably, osteosarcoma. As used herein, the term bone cancer refers to chondrosarcoma, Ewing's sarcoma, osteosarcoma or metastatic bone cancer. ([0026]). Example 9 discloses administering after surgery. ([0108]).
Canal Barnils does not specifically disclose a STAT3 inhibitor.
Zuo discloses a study, which investigated the antitumor effect of napabucasin (NP) (BBI608), an inhibitor of STAT3 on osteosarcoma in vitro and in vivo, Zuo reports the following results: “Our results show that NP treatment decreases cell viability and induces apoptosis in several osteosarcoma cell lines. NP treatment suppresses both expression and phosphorylation of STAT3 in addition to blocking STAT3-mediated transcription and downstream target proteins in osteosarcoma cells. Furthermore, NP inhibits protein synthesis through regulation of the eukaryotic initiation factor 4E (eIF4E) and eIF4E-binding protein 1 (4E-BP1). NP also inhibits the progression of osteosarcoma tumors and metastasis in vivo in an orthotopic tibial model of osteosarcoma.” Zuo concludes: “Taken together, our investigation reveals that NP acts through a novel mechanism and inhibits osteosarcoma growth and metastasis, and could be investigated clinically for treating osteosarcoma patients alone or in combination with other drugs.” (Abstract). Zuo further discloses STAT3 inhibitor prevented phosphorylation at tyrosine 705. (p. 9, col. 2- p. 10, col. 1).
Accordingly, it would have been obvious to a person of skill in the art before the effective filing date of the claimed invention to combine the teachings of Canal Barnils and Zuo in order to practice Applicant’s claimed composition, combination and method f treating cancer with a reasonable expectation of success. The skilled artisan would have been motivated to do so because STAT3 inhibitors are known for treating osteosarcoma, as disclosed in Zuo, and suggested to be used alone or in combination. Further motivation to do so is because Canal Barnils discloses another line of treatment comprising a liquid or hydrogel with RONS, to include specifically for the treatment of osteosarcoma. Although neither reference explicitly discloses administration simultaneously or sequentially, they both disclose administration in combination with other drugs. Accordingly, it would have been obvious to one of skill in the art to adjust the timing of administration based on considerations of drug pharmacokinetics and efficacy. Thus, co-administration would have been obvious as both drugs are known for treating the same kind of cancer, and their co-administration would afford the opportunity to reduce dose of each drug individually while potentially targeting more than one cancer pathway.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SVETLANA M IVANOVA whose telephone number is (571)270-3277. The examiner can normally be reached 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SVETLANA M IVANOVA/Primary Examiner, Art Unit 1627
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