Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
Claims 19-33 are currently pending.
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).
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NONPROVISIONAL:
1. Claims 19-33 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-28 of U.S. Patent No. 10087175 (hereinafter referred to as Hawkins) in view of Berge (J. of Pharmaceutical Sci. Vol. 66, No. 1, January 1977. 1-19) and Beijnen (Cancer Treatment Reviews 1999; 25: 83–101).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a genus of erastin-derivative conjugates
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, compositions thereof, and methods of treating cancer therewith. Both compositions include carriers. Methods of use include treating pancreatic cancer and synovial sarcoma with the same classes and species of additional agents as well as the same co-therapies like radiation and surgery.
Regarding Claim 3, an n of 5 may vary to be an n of 1 or 2 as claimed in the instant formula. Not only does Hawkins teach variation in the alkyl chain of the sigma-2 binding moiety, but compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09. Because the homologs are similar in scope, limited to a finite genus of under 20 compounds, and directed to the same use, one of skill in the art would find obvious and expect the variation taught by Hawkins to result in similarly active and useful compounds. See also MPEP 2144.08.
Hawkins teaches different oxalate or hydrochloride salts than instant Claim 22.
However, Berge teaches a limited list of useful pharmaceutical salts including “methanesulfonic acid” or methanesulfonate (Page 5, Table III). Berge teaches the formation of said salt with the exemplary pharmaceutical improved solubility. Further, Berge provides the following more general guidance “the chemical, biological, physical, and economic characteristics of medicinal agents can be manipulated and, hence, often optimized by conversion to a salt form” (Page 1). Therefore, one of skill in the art seeking to form a salt as described in Hawkins would find it obvious to form a methanesulfonate salt to attempt to improve the drug solubility or modify any of the above characteristics. One of skill in the art would expect success in doing so as well as be particularly motivated to select methanesulfonate because improving aqueous solubility of a conjugate possessing a long nonpolar alkyl chain is advantageous in biological aqueous contexts. One forming a more soluble form would also find it obvious to form an aqueous (water) solution for administration because the conferred solubility would allow for more drug to be administered in a smaller solution volume using a carrier which is cheap and plentiful like water.
Further, instant Claim 22 as written does not require that the composition contain the conjugate in a salt form, only that the salt form, if present, be methanesulfonate.
Hawkins does not teach particular routes for delivery.
However, Beijnen teaches common chemotherapeutic routes include oral administration for convenience and intraperitoneal administration for delivery to a cavity which would be advantageous near an affected organ for example (Abstract; Page 90, Left Col.). One of skill in the art would expect success in using said routes because Beijnen offers a general review of the chemotherapeutic routes rather than identifying and restricting the teachings to a single agent.
Since both claim sets teach the same conjugates for the same use in treating the same cancers, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Hawkins. Claims 19 and 22-31 are anticipated over Hawkins Claims 1-2, 4-9, 11-16, 18, 20-24, and 26-28.
2. Claims 19-33 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-17 of U.S. Patent No. 10344029 (hereinafter referred to as Hawkins) in view of Berge (J. of Pharmaceutical Sci. Vol. 66, No. 1, January 1977. 1-19) and Beijnen (Cancer Treatment Reviews 1999; 25: 83–101).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a genus of erastin-derivative conjugates, compositions thereof, and methods of treating cancer therewith. Both compositions include carriers. Methods of use include treating pancreatic cancer and synovial sarcoma, with the same classes and species of additional agents as well as the same co-therapies like radiation and surgery.
Hawkins teaches a broader genus of Formula III:
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, wherein Y is
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or Erastin and the Z1-Z2-Z3 linker comprises C1-C10alkylenes. Several combinations of alkyl linkers as specified in Hawkins Claim 5 would yield a compound of Formula IV as described in instant Claim 19, wherein the total carbon count in the alkyl chain is six or seven. One of skill in the art seeking to form a conjugate described by Hawkins would find it obvious to select the above parameters such that an alkyl chain encompassed by Fomrula IV results and expect success in treating the same cancers because Hawkins teaches the broader genus with variability as being used for treating the same pancreatic cancer and synovial sarcoma.
Hawkins teaches different oxalate and hydrochloride salts than instant Claim 22.
However, Berge teaches a limited list of useful pharmaceutical salts including “methanesulfonic acid” or methanesulfonate (Page 5, Table III). Berge teaches the formation of said salt with the exemplary pharmaceutical improved solubility. Further, Berge provides the following more general guidance “the chemical, biological, physical, and economic characteristics of medicinal agents can be manipulated and, hence, often optimized by conversion to a salt form” (Page 1). Therefore, one of skill in the art seeking to form a salt as described in Hawkins would find it obvious to form a methanesulfonate salt to attempt to improve the drug solubility or modify any of the above characteristics. One of skill in the art would expect success in doing so as well as be particularly motivated to select methanesulfonate because improving aqueous solubility of a conjugate possessing a long nonpolar alkyl chain is advantageous in biological aqueous contexts. One forming a more soluble form would also find it obvious to form an aqueous (water) solution for administration because the conferred solubility would allow for more drug to be administered in a smaller solution volume using a carrier which is cheap and plentiful like water.
Further, instant Claim 22 as written does not require that the composition contain the conjugate in a salt form, only that the salt form, if present, be methanesulfonate.
Hawkins does not teach particular routes for delivery.
However, Beijnen teaches common chemotherapeutic routes include oral administration for convenience and intraperitoneal administration for delivery to a cavity which would be advantageous near an affected organ for example (Abstract; Page 90, Left Col.). One of skill in the art would expect success in using said routes because Beijnen offers a generic review of the chemotherapeutic routes rather than identifying and restricting the teachings to a single agent.
Since both claim sets teach the same conjugates for the same use in treating the same cancers, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Hawkins.
3. Claims 19-33 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-18 of U.S. Patent No. 10975069 (hereinafter referred to as Hawkins).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a genus of Erastin-derivative conjugates
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, compositions thereof, and methods of treating cancer therewith. Both compositions include carriers which are water or saline for oral or intraperitoneal delivery. Salts of the conjugate are recited including methanesulfonate. Methods of use include treating pancreatic cancer and synovial sarcoma with the same classes and species of additional agents as well as the same co-therapies like radiation and surgery.
Regarding Claim 3, an n of 5 may vary to be an n of 1 or 2 as claimed in the instant formula. Not only does Hawkins teach variation in the alkyl chain of the sigma-2 binding moiety, but compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP 2144.09. Because the homologs are similar in scope, limited to a finite genus of under 20 compounds, and directed to the same use, one of skill in the art would find obvious and expect the variation taught by Hawkins to result in similarly active and useful compounds. See MPEP 2144.08.
Since both claim sets teach the same conjugates for the same use in treating the same cancers, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Hawkins. Claims 19-33 are anticipated over Hawkins Claims 1-2 and 4-18.
Allowable Subject Matter
The closest prior art to the examined claims is found in McDunn (US20090176705) which teaches the following molecule SW 141:
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, wherein the sigma-2 ligand is conjugated to a protected aspartate (Abstract). McDunn teaches peptide moieties or mimetics or small molecule moieties in place of the protected group above (Para 8-24). McDunn teaches the same sigma-2 moiety as the instant claims but does not teach or suggest the Erastin moiety. McDunn does not suggest the orientation of a theoretically attached Erastin moiety, nor does McDunn teach or make predictable that both the sigma-2 ligand and Erastin would retain their respective apoptotic and ferroptotic capabilities when chemically tethered.
Further, applicant provides synergistic dosing results beginning at Fig. 4A suggesting greatly improved conjugate efficacy as compared to either moiety alone or administered together, untethered.
Lastly, Hashim (Molecular Oncology 8 (2014) 956-967; 1/21/2025 IDS), in reference to conjugate formation with sigma-2 ligands, teaches “[t]he question that arises when combining two unrelated molecules is whether this linkage will change the active domains of the individual components of the conjugate” (Page 959, 3. Results). This question with respect to a modification with Erastin is not resolved by any teaching in the cited art. It is not clear that the activity of the two individual molecules will be retained when forming conjugates at the time of the earliest filing date—let alone exert increased synergistic efficacy when tethered in the claimed manner. It is also noted that Hashim does not teach or suggest Erastin as a conjugated moiety for use in this art context. Therefore, the instant claims are not obvious let alone anticipated over the prior art.
Conclusion
No claim is allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 8:30am - 4:30pm EST.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
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