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 Status
Claims 1-14 are currently pending.
Claims 1-14 are being examined in this application.
Priority
This application is filed under 35 U.S.C 371 of PCT/JP2022/0028871 (filed on 07/27/2022), which claims priority to foreign applications JAPAN 2021-122073 (filed on 7/27/2021).
Information Disclosure Statement
All IDS filed have been considered. See the attached PTO 1449 forms.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification. MPEP 608.01.
Claim Objections
Applicant is advised that should claim 12 (or 13) be found allowable, claim 13 (or 12) will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
112(b) Rejection
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 3 and 5 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.
Claims 3 and 5 recite the limitation "the amino acid sequence" in the last line of the claims. There is insufficient antecedent basis for this limitation in the claims. The claim recites both antibody sequence and the CAPRIN-1 sequence of various SEQ ID NOs. It is not clear to which sequence the said phrase is referring.
112(a) Rejection(s)
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.
Written Description Rejection
Claims 3 and 5 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.
The instant claims recite antibody or fragments thereof that has immunological activity with the CAPRIN-1 protein of various sequences that can share 80% or more identities with different SEQ ID NOs as recited in claims 3 and 5.
To satisfy the written description requirement, applicants may convey reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention.
Applicants may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. See, e.g., Vas-Cath, 935 F.2d at 1565, 19 USPQ2d at 1118.
The written description requirement of 35 U.SC. 112 exists independently of enablement requirement, and the requirement applies whether or not the case involves questions of priority. The requirement applies to all inventions and includes chemical inventions. The fact that the patent is directed to method entailing use of compounds, rather than to compounds per se, does not remove patentee’s obligation to provide a description of the compound sufficient to distinguish infringing methods from non-infringing methods. See Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ 2d 1886, 1890-93 (Fed. Cir. 2004).
With regard to the description requirement, applicants’ attention is invited to consider the decision of the Court of Appeals for the Federal Circuit, which holds that a “written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula [or] chemical name,’ of the claimed subject matter sufficient to distinguish it form other materials.” University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1405 (1997), quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original) [The claims at issue in University of California v. Eli Lilly defined the invention by function of the claimed DNA (encoding insulin)].
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species or by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F. 3d at 1568, 43 USPQ2d at 1406.
Each of claims 3 and 5 is drawn to a genus of amino acid sequences. Each claim recites “… an amino acid sequence having 80% or more sequence identity with” a list of various SEQ ID NOs. Neither the instant specification nor the claims have demonstrated common structure and/or function for the claimed genus of amino acid sequences that would have the same function as the CAPRIN-1 protein or that can be bound by the various anti-CAPRIN-1 antibodies. In addition, no representative numbers of species for each claimed genus of sequence are provided to show possession of the claimed genus of proteins or fragments thereof that can be bound by the various anti-CAPRIN-1 antibodies.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. (see MPEP 2163 II). In this case, the instant application did not provide the core sequences that would provide the CAPRIN-1 protein function or that can be bound by the various anti-CAPRIN-1 antibodies. The only examples are the sequences with the 100% matching sequences to the SEQ ID NOs that are the full CAPRIN-1 protien or fragments thereof. The instant specification has not provided any examples where proteins that share 40% or more identify with the CAPRIN-1 protein (or fragments thereof) would still have the same binding affinity and function.
Therefore, applicants are not in possession of the entire claimed genus of antibody sequences.
Scope of Enablement Rejection
Claims 1-14 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for using a combination of anti-CAPRIN-1 antibody and HDACi for treating certain type of cancer, does not reasonably provide enablement for preventing cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. §112, first paragraph, have been described In re Wands, 8 USPQ2d 1400(1988). They are:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The predictability or lack thereof in the art
5. The level of skill in the art;
6. The amount of direction or guidance present;
7. The presence or absence of working examples;
8. The quantity of experimentation needed.
The breadth of the claims / The nature of the invention
The breadth of the claims are drawn to any combination of any protein (antibodies or fragments thereof) that have immunological activity with CAPRIN-1 protein, and any HDACi, and method of using such a genus of pharmaceutical composition for treating and/or preventing any cancer. The nature of the invention in the instant claims are composition that have the property of “treating and/or preventing” any cancer, and methods of treating and preventing any cancer.
The state of the prior art/ The predictability or lack thereof in the art
Preventing various type of cancer using combination therapy is highly unpredictably. Currently there is no known method of total “prevention” of any cancer. For certain types of cancer, surgery and certain vaccines maybe effective at potential prevention. Further, treating various cancer using combination therapy based on HDACi and antibodies is also unpredictable.
The level of one of ordinary skill
The level of skill would be high, most likely at the Ph.D. level.
The amount of direction or guidance present / The presence or absence of working examples
The only guidance present in the instant specification is using specific anti-CAPRIN-1 antibodies and romidepsin (or Panobinostat) with cells in vitro. There are no working examples of using the combination to treat cancer patients. Further, there is no example of showing “preventing” cancer using the combination.
The quantity of experimentation needed
Due to the unpredictabilities of using the combination of (any) anti-CAPRIN-1 antibodies and (any) HDACi to treat and/or prevent any cancer in vivo, undue experimentation would be required. The art has not demonstrated any combination of the two drugs (antibodies and HDACi) can be used to prevent any cancer or even treat certain types of cancer. Because the instant specification only provides guidance for in vitro (i.e. cell based assay) two particular combination, undue experimentation would be required to practice claimed pharmaceutical composition and method of preventing or even treating any cancer.
Conclusion
Therefore based on the evidences as a whole regarding each of the above factors (e.g. factors 1-8), the specification, at the time the application was filed, does not satisfy the enablement requirement for the instant 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.
Okano, Laengle & Medon
Claims 1-14 are rejected under 35 U.S.C. 103(a) as being unpatentable over Okano et al (US 9115200; 8/25/2015), in view of Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The instant claims recite a medicament for treatment and/or prevention of cancer, comprising an antibody or a fragment thereof having an immunological reactivity with CAPRIN-1 protein, and an HDAC (histone deacetylase) inhibitor together or separately in combination.
Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer (e.g. Abstract).
For claims 1 and 12-13, Okano teaches pharmaceutical composition comprising an antibody or fragments thereof for CAPRIN-1 (e.g. Abstract; Claims 1+). The reference also teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+).
For claims 3 and 5, the reference teaches sequences for CAPRIN-1 protein (e.g. claim 1).
For claim 4, the antibodies of the reference would bind to the extracellular region of the CAPRIN-1 protein since they share the same amino acid sequences.
For claim 6, Okano teaches monoclonal antibodies (e.g. claim 1).
For claims 4, 7-8, Okano teaches anti-CAPRIN-1 antibodies with heave chain and light chain of SEQ ID NOS: 43 and 47 (e.g. col. 12, ll. 51+), which are exact match to the instant SEQ ID NOs: 39 and 43. The instant SEQ ID NOs comprises the HCDRs and LCDRs of SEQ ID Nos: 36-38 and 40-42, respectively. The antibodies of the reference would bind to the extracellular region of the CAPRIN-1 protein since they have the same amino acid sequences.
For claim 9, Okano teaches the antibody can be humanized, or a single chain antibody. (e.g. claim 10).
For claims 10-11, Okano teaches the pharmaceutical composition is for treating various cancer where CAPRIN-1 is expressed in the tumor cell including breast cancer (e.g. Abstract; col.36, lines 24+; col.23).
For claims 14, Okano teaches treating cancer by administering the antibody and an antitumor agent (e.g. claims 13, 11; col.15).
Okano et al do not explicitly teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
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.
‘418 Patent
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 8709418 (hereinafter referred to as ‘418 Patent) in view of Okano et al (US 9115200; 8/25/2015), in view of Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The ‘418 Patent claims the followings:
A pharmaceutical composition for the treatment of a CAPRIN-1-expressing cancer or preventing the recurrence of a CAPRIN-1-expressing cancer, comprising an antibody or a fragment thereof as an active ingredient that has immunological reactivity with a CAPRIN-1 protein, wherein the antibody comprises a heavy chain variable region comprising SEQ ID NOS: 39, 40, and 41 and a light chain variable region comprising SEQ ID NOS: 43, 44, and 45 or a fragment thereof having anti-tumor activity.
The pharmaceutical composition according to claim 1, wherein the cancer is breast cancer, brain tumor, leukemia, lymphoma, lung cancer, mastocytoma, renal cancer, uterine cervix cancer, esophageal cancer, gastric cancer, bladder cancer, or colorectal cancer.
3. The pharmaceutical composition according to claim 1, wherein the antibody is a human antibody, humanized antibody, chimeric antibody, single chain antibody, or bispecific antibody.
6. A pharmaceutical combination for treating cancer, comprising the pharmaceutical composition of claim 1 and a pharmaceutical composition containing an antitumor agent.
8. A method for the treatment of a CAPRIN-1-expressing cancer or preventing the recurrence of a CARRIN-1-expressing cancer in a subject with cancer, comprising administering a therapeutically effective amount of the pharmaceutical composition comprising the pharmaceutical combination of claim 6 to a subject in need thereof.
The ‘418 Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
‘398 Patent
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 8828398 (hereinafter referred to as ‘398 Patent) in view of Okano et al (US 9115200; 8/25/2015), in view of Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The ‘398 Patent claims the followings:
A method for treating a CAPRIN-1 expressing cancer and/or preventing the recurrence of a CAPRIN-1 expressing cancer, comprising administering to a subject an antibody or a fragment thereof which has immunological reactivity with a polypeptide that consists of the amino acid sequence of SEQ ID NO: 37, and has immunological reactivity with CAPRIN-1 polypeptide.
A method for treating a CAPRIN-1 expressing cancer and/or preventing the recurrence of a CAPRIN-1 expressing cancer, comprising administering to a subject a pharmaceutical combination comprising:
(i) an antibody or fragment thereof that has immunological reactivity with a polypeptide that consists of the amino acid sequence of SEQ ID NO:37, and that has immunological reactivity with CAPRIN-1 polypeptide; and
(ii) an antitumor agent.
The ‘398 Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
‘160 Patent
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 8937160 (hereinafter referred to as ‘160 Patent) in view of Okano et al (US 9115200; 8/25/2015), in view of Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The ‘160 Patent claims the followings:
1. A method for treating a CAPRIN-1-expressing cancer, comprising administering to a subject having said cancer a monoclonal antibody or an antigen-binding fragment thereof, wherein said monoclonal antibody or antigen-binding fragment thereof specifically binds a polypeptide consisting of the amino acid sequence of SEQ ID NO: 37.
2. A method for treating a CAPRIN-1-expressing cancer, comprising administering a pharmaceutical combination comprising:
i. a monoclonal antibody or an antigen-binding fragment thereof as an active ingredient that specifically binds a polypeptide consisting of the amino acid sequence of SEQ ID NO: 37; and
ii. a pharmaceutical composition containing an antitumor agent in combination to a subject having said cancer.
The ‘160 Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
‘740 Patent
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 8911740 (hereinafter referred to as ‘740 reference Patent) in view of Okano et al (US 9115200; 8/25/2015), in view of Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference Patent claims the followings:
1. A method for treating and/or preventing recurrence of a CAPRIN-1 expressing cancer, comprising administering to a subject an antibody or a fragment thereof having immunological reactivity with a polypeptide that consists of the amino acid sequence of SEQ ID NO: 37.
2. A method for treating and/or preventing recurrence of a CAPRIN-1 expressing cancer, comprising administering to a subject a pharmaceutical combination comprising an antitumor agent, and
an antibody or a fragment thereof as an active ingredient that has immunological reactivity with a partial polypeptide of CAPRIN-1, wherein CAPRIN-1 is any of the even-numbered sequences of SEQ ID NOS: 2 to 30, and wherein the partial polypeptide consists of the amino acid sequence of SEQ ID NO: 37, or
an antibody or a fragment thereof having immunological reactivity with a polypeptide that consists of the amino acid sequence of SEQ ID NO: 37.
The reference Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
‘074 Patent
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 9175074 (hereinafter referred to as ‘074 reference Patent) in view of Okano et al (US 9115200; 8/25/2015), in view of Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference Patent claims the followings:
6. A pharmaceutical combination for treatment of CAPRIN -1- expressing cancer, comprising a pharmaceutical composition according to claim 4 and a pharmaceutical composition comprising an antitumor agent.
15. A method for treating CAPRIN-1-expressing cancer, comprising administering an antibody or a fragment thereof according to claim 6.
The reference Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
‘187 Patent
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9180187 (hereinafter referred to as ‘187 reference Patent) in view of Okano et al (US 9115200; 8/25/2015), in view of Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference Patent claims the followings:
1. A method for treating and/or preventing recurrence of a CAPRIN-1 expressing cancer, comprising:
administering a medicament to a subject suspected of having a cancer,
wherein the medicament comprises a combination of an antibody or a fragment thereof having immunological reactivity with a CAPRIN-1 protein, and one or two or more types of antitumor agents,
wherein the antibody or fragment and the antitumor agent or antitumor agents are combined together or separately,
wherein the antibody or fragment and the antitumor agent are not conjugated together,
wherein the cancer expresses the CAPRIN-1 protein on the cell surface of the cancer and the antibody or fragment binds specifically to the extracellular region of a CAPRIN-1 protein existing on the surface of a cancer cell.
The reference Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
‘188 Patent
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 9180188 (hereinafter referred to as ‘188 reference Patent) in view of Okano et al (US 9115200; 8/25/2015), in view of Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference Patent claims the followings:
4. A pharmaceutical composition for treatment of caprin-1-expressing cancer, comprising an antibody or a fragment thereof according to claim 1 as an active ingredient.
6. A pharmaceutical combination for treatment of caprin-1-expressing cancer, comprising a pharmaceutical composition according to claim 4 and a pharmaceutical composition comprising an antitumor agent.
15. A method for treating caprin-1-expressing cancer, comprising administering a pharmaceutical combination according to claim 6 to a test subject.
The reference Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
‘334 Patent
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 9181334 (hereinafter referred to as ‘334 reference Patent) in view of Okano et al (US 9115200; 8/25/2015), in view of Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference Patent claims the followings:
4. A pharmaceutical composition for treatment of caprin-1-expressing cancer, comprising the antibody or the fragment thereof according to claim 1 as an active ingredient.
5. The pharmaceutical composition according to claim 4, wherein the cancer is breast cancer, kidney cancer, pancreatic cancer, colorectal cancer, lung cancer, brain tumor, gastric cancer, uterine cervix cancer, ovary cancer, prostate cancer, urinary bladder cancer, esophageal cancer, leukemia, lymphoma, fibrosarcoma, mastocytoma, or melanoma.
6. A pharmaceutical combination for treatment of caprin-1-expressing cancer, comprising the pharmaceutical composition according to claim 4 and a pharmaceutical composition comprising an antitumor agent.
15. A method for treating caprin-1-expressing cancer, comprising administering the pharmaceutical combination according to claim 6, to a subject.
The reference Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
‘348 Patent
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 9181348 (hereinafter referred to as ‘348 reference Patent) in view of Okano et al (US 9115200; 8/25/2015), in view of Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference Patent claims the followings:
1. An antibody or a fragment thereof which has immunological reactivity with a CAPRIN-1 protein, the antibody or the fragment thereof comprising a heavy chain variable region comprising complementarity determining regions of SEQ ID NOs: 5, 6, and 7 and a light chain variable region comprising complementarity determining regions of SEQ ID NOs: 9, 10, and 11.
2. The antibody or the fragment thereof according to claim 1, wherein the antibody is a human antibody, a humanized antibody, a chimeric antibody, a single-chain antibody, or a multispecific antibody.
3. The antibody or the fragment thereof according to claim 1, wherein the antibody or the fragment thereof is conjugated with an antitumor agent.
15. A method for treating CAPRIN-1-expressing cancer, comprising administering an antibody or a fragment thereof according to claim 3 to a test subject.
The reference Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
‘200 Patent
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9115200 (hereinafter referred to as ‘200 reference Patent) in view of Okano et al (US 9115200 Spec; 8/25/2015), Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference Patent claims the followings:
11. A pharmaceutical combination for treating and/or inhibiting the recurrence of a cancer, comprising the pharmaceutical composition of claim 1, and a pharmaceutical composition containing an antitumor agent.
12. A method for treating and/or inhibiting the recurrence of a cancer in a subject, comprising administering to the subject the monoclonal antibody of claim 4 or an antigen binding fragment thereof or the pharmaceutical composition of claim 1.
13. A method for treating and/or inhibiting the recurrence of a cancer in a subject, comprising administering to the subject the pharmaceutical combination of claim 11.
The reference Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
Other Patents
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent Nos. 9273128; 9273130; 9409993; 9416193; 9428581; 9266958; 9260513; 9573993; 9862774; 1137401 in view of Okano et al (US 9115200 Spec; 8/25/2015), Laengle et al. (Histone deacetylase inhibitors valproic acid and vorinostat enhance trastuzumab-mediated antibody dependent cell-mediated phagocytosis. Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (HDAC inhibitor Panobinostat engages host innate immune defenses to promote the tumoricidal effects of Trastuzumab in HER2+ tumors. Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference Patents claim various CAPRIN-1 antibodies in combination with an antitumor agent, and methods of treating cancer using such a combination. For sake of brevity, only one reference patent’s relevant claims are included below as examples.
13. A pharmaceutical composition for treatment of cancer, comprising the antibody or the fragment thereof according to claim 1 as an active ingredient, wherein the cancer is a CAPRIN-1 expressing cancer.
14. The pharmaceutical composition according to claim 13, wherein the cancer is breast cancer, kidney cancer, pancreatic cancer, colorectal cancer, lung cancer, brain tumor, gastric cancer, uterine cervix cancer, ovary cancer, prostate cancer, urinary bladder cancer, esophageal cancer, leukemia, lymphoma, fibrosarcoma, mastocytoma, or melanoma.
15. A pharmaceutical combination for treatment of cancer, comprising a pharmaceutical composition according to claim 13 and a pharmaceutical composition comprising an antitumor agent.
17. A method for treating cancer, comprising administering the antibody or the fragment thereof according to claim 1, wherein the cancer is a CAPRIN-1 expressing cancer.
The reference Patent does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
‘538 Application
Claims 1-14 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-13, 16-20 of copending Application No. 17/910,538 (hereinafter referred to as the ‘538 reference application) in view of Okano et al (US 9115200; 8/25/2015), Laengle et al. (Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (Cancer Research. Vol.77(10): 2594-2606; 2017).
(NOTE the reference application has been allowed but is yet to be issued. This rejection will be converted to non-provisional rejection once it is issued.)
The reference application claims
A medicament for treatment of cancer, comprising (i) an antibody or a fragment thereof having an immunological reactivity with CAPRIN-1 protein, (ii) ramucirumab, and (iii) paclitaxel, nab-paclitaxel, or a combination of paclitaxel and nab- paclitaxel, wherein the taxane-based drug is paclitaxel, docetaxel, and/or nab-paclitaxel. wherein the cancer is cancer expressing CAPRIN-1 protein on a cell membrane surface.
18. (Currently Amended) A method for treating and/or preventing cancer, comprising administering (ii an antibody or a fragment thereof having an immunological reactivity with CAPRIN-1 protein, (ii) ramucirumab, and (iii) paclitaxel, nab-paclitaxel, or a combination of paclitaxel and nab- paclitaxel, to a subject in need thereof, wherein the cancer is cancer expressing CAPRIN-1 protein on a cell membrane surface.
The reference Application does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
This is a provisional nonstatutory double patenting rejection.
‘522 Application
Claims 1-14 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 17910522 (hereinafter referred to as the ‘522 reference application) in view of Okano et al (US 9115200 Spec; 8/25/2015), Laengle et al. (Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference Application claims a medicament comprising the CAPRIN-1 antibody and another antitumor drug, and the method of using the medicament for treating cancer as recited in claims 1, 4, 17, for examples.
The reference Application does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
This is a provisional nonstatutory double patenting rejection.
‘549 Applications
Claims 1-14 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 17910549 (hereinafter referred to as the ‘549 reference application) in view of Okano et al (US 9115200 Spec; 8/25/2015), Laengle et al. (Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference Application claims a medicament comprising the CAPRIN-1 antibody and another antitumor drug, and the method of using the medicament for treating cancer as recited in claims 1, 2, 4, 18, for examples.
The reference Application does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
This is a provisional nonstatutory double patenting rejection.
Other Applications
Claims 1-14 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of copending Application No. 18573750; 18573641; 18292094; 18292656; 19103152; 19103661; 19105394; 19105407; 19105447 in view of Okano et al (US 9115200 Spec; 8/25/2015), Laengle et al. (Journal for ImmunoTherapy of Cancer. Vol.8: 1-9; published online 1/2/2020), and if necessary in view of Medon et al. (Cancer Research. Vol.77(10): 2594-2606; 2017).
The reference applications’ claim various CAPRIN-1 antibodies in combination with an antitumor agent, and methods of treating cancer using such a combination. For sake of brevity, only one reference application’s relevant claims are included below as examples.
The ‘750 reference Application, for example, claims a medicament comprising the CAPRIN-1 antibody and another antitumor drug, and the method of using the medicament for treating cancer as recited in claims 1 and 19, for examples.
The reference Application does not explicitly claim specific antibody sequences as recited in claims 7 and 8, teach the antitumor agent is an HDAC inhibitor of claim 1, and specifically romidepsin or panobinostat as recited in claim 2.
However, Okano et al, throughout the reference, teach pharmaceutical composition comprising antibodies that bind to CAPRIN-1 protein for treatment of cancer, as discussed supra.
Laengle et al., throughout the publication, teach combination cancer treatment with HDAC and an antibody, trastuzumab (which is an antibody against HER2 expressed in breast cancer tumor cells) (e.g. Abstract; p.1). The reference teaches that “antibody-dependent cell mediated phagocytosis (ADCP) and cytotoxicity (ADCC) as major mechanisms for action for most mAB, such as trastuzumab” (e.g. p.1, right col., para 1). The reference also teaches “HDACi have additive or synergistic treatment effects in combination with the mAB” (e.g. pp.1-2 bridging para). The reference also teaches that combination of HDACi Panobinostat and trastuzumab has show “synergistic effect” (citing the Medon reference), and that HDACi induced immunomodulation that is essential for therapeutic effect (e.g. p.2, left col., para 1). The Laengle reference also concludes that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.)
The Medon reference teaches that HDACi, Panobinostat has “immune-enhancing effects” when combined with an antibody against a tumor cell expression protein (e.g. Abstract). The reference also teaches that Panobinostat has “manageable toxicity profile” and “could greatly complement standard chemotherapy” when “combined with trastuzumab.” (e.g. p.2604, right col., last para).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine a HDACi such as Panobinostat with an antibody, such as anti-CAPRIN-1 antibody that binds to a protein that is highly expressed in cancer tumor cells, for treating cancer, because Okano, Laengle and Medon all teach combination therapy with an antitumor agent (such as a HDACi) and an antibody. As discussed above, Okano teaches a “pharmaceutical combination” comprising the antibody and “an antitumor agent” that can be various known drugs that treat tumor including ones that are inhibitors of tumor cell associated proteins (e.g. claim 11; col.14-15 bridging para). The Okano reference also teaches that the antibody contains regions that are involved in “antibody-dependent cell -mediated cytotoxicity (ADCC), phagocytosis via binding to an Fcγ receptor…” (e.g. col.9, ll. 30+). The reference also teaches the benefit of combination therapy for cancer including “Through administration of the antibody of the present invention in combination with an antitumor agent, even higher therapeutic effects can be obtained” (e.g. col.15, lines 30+). The enhanced therapeutic effects of the combination therapy is also disclosed in Laengle and Medon where a different antibody (but with similar mechanism of action) was used. The Laengle reference specifically teaches that “HDACi… enhances trastuzumab-mediated phagocytosis and trastuzumab-independent cytotoxicity” and “support a rationale combined treatment approach” with HDACi and an antibody such as trastuzumab (e.g. p.8, last para.). Thus, it would have been obvious to one of ordinary skill in the art to combine anti-CAPRIN-1 antibody with a HDACi such as Panobinostat to treat cancer so to achieve the desired synergistic therapeutic effects including phagocytosis and ADCC to treat cancers with tumor cells that express CAPRIN-1.
A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all three cited reference have demonstrated combination therapy for treating cancer.
This is a provisional nonstatutory double patenting rejection.
Conclusion and Correspondence
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUE LIU whose telephone number is (571)272-5539. The examiner can normally be reached M-F 9-5.
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 (director), Jennifer Michener can be reached at 571-272-1424. 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.
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
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