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 Objections
Claims 72 and 73 are objected to because of the following informalities:
Claim 72 states, “each A is an independently selected from a hydrogen…” should state “each A is independently selected from hydrogen…”
Formula I in Claim 72 is blurry, and should be in black ink
Claim 73 states “…or aC1-C12 alkoxyalkyl”, should state “…or a C1-C12 alkoxyalkyl”
Claim 73 states “M is metal”, should state “M is a metal”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 71-85 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.
Claim 71 states “an active agent at a loading dose in an amount of about 0.05 mg/kg to about 1 mg/kg times the activity equivalent of BMX-001”, and this statement is determined to be indefinite. In the specification, the term “activity equivalent” is not defined, and the “activity equivalent” is determined by those of skill in the art with assays such as a “cytochrome c assay and/or pulse radiolysis”. It is unclear how to calculate the activity equivalent from the results of the assays, and what the term activity equivalent means in reference to BMX-001. It is also unclear what activity the claim is meant to reference as BMX-001 has more than one utility – is it meant to be the activity equivalent when used to potentiate radiation and/or chemotherapy?
Claim 72 includes a compound of Formula I, see below, and there is an R group included in the Formula that does not appear to be bonded to any variable. The R variable is not bonded to any other variable, and does not include a charge. Also, Formula I on pg. 26 of the specification does not include the floating R variable. It is unclear how the R variable is bonded in the molecule, and if it a misprint of Formula I included in the specification.
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Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 71-75, 78, 82, 83-85, 86, 87, and 89 are rejected under 35 U.S.C. 103 as being unpatentable over Rabbani (Zahid Rabbani et al., “Antiangiogenic action of redox-modulating Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP5+, via suppression of oxidative stress in a mouse model of breast tumor”, Free Radical Biology and Medicine, Volume 47, Issue 7, Pgs. 992-1004, Pub. Date: October 2009) in view of Moeller (Benjamin Moeller et al., “A MANGANESE PORPHYRIN SUPEROXIDE DISMUTASE MIMETIC ENHANCES TUMOR RADIORESPONSIVENESS”, Int. J. Radiation Oncology Biol, Volume 63, Issue 2, Pgs. 545-552, Pub. Date: May 2005) and in further view of Rajic (Zrinka Rajic et al., “A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity”, Free Radical Biology and Medicine, Volume 52, Issue 9, Pgs. 1828-1834, Pub. Date: May 1, 2012).
Regarding Claim 71, Rabbani discloses [Mn(III) tetrakis(N-ethylpyridinium-2-yl)porphyrin], herein MnTE-2 PyP5+ , see below, as a manganese porphyrin superoxide that acts as an anticancer agent for breast tumors in mice (Abstract).
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Regarding the claim limitation of the loading dose and maintenance dosing, Rabbani discloses “loading dose of MnTE-2-PyP5+ may be necessary for a certain time period, followed by a maintenance dosing. Further studies will optimize the dosing regimen whereby anti-cancer effects may be enhanced.” (Pg. 998). The courts have found that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); Therefore it would be obvious to optimize to optimize the maintenance dose to about 25% to about 75% of the loading dose, because it was already known in the art to administer a maintenance dose that is less than the loading dose. One of ordinary skill could easily optimize the percentage of the maintenance dose, to arrive at the claimed limitations.
Regarding Claim 85, Rabbani discloses “The compound was prepared in sterile phosphate-buffered saline (PBS) and administered twice daily by subcutaneous injections (low dose, 2 mg/kg/day, and high dose, 15 mg/kg/day).” (Pg. 994).
Rabbani discloses that MnTE-2 PyP5+ was administered at 6 mg/kg, 1 hour before each of three radiation doses, or (2) MnTE-2 PyP5+ (6mg/kg) administered 1 h, 13 h, and 25 h after the final radiation dose (Pg. 549).
Rabbani does not disclose MnTE-2 PyP5+ administered during or following radiation and or chemotherapy exposure or the activity equivalent of BMX-001.
Moeller discloses that [Mn(III) tetrakis(N-ethylpyridinium-2-yl)porphyrin], herein MnTE-2 PyP5+ , as a manganese porphyrin superoxide that enhances tumor radio responsiveness.
Moeller does not disclose the activity equivalent of BMX-001.
Rajic teaches a toxicity and efficacy study including BMX-001 administered as single or multiple doses as low as 0.05 mg/kg and showing remarkable efficacy for animal models of oxidative stress (Abstract and Pg. 1831). Rajic also discloses BMX-001 administered as intraperitoneal (ip) injections of saline, 0.5, 1.5, 4.5, or 9 mg/kg/day for 7 days (the total daily doses were given in two increments) (Pg. 1830).
Regarding Claims 72 and 73, BMX-001 disclosed in Rajic overlaps with instant Formula (I), and (B1). To map BMX-001 with instant Formula (I), R is a substituted heteroaryl, A is Hydrogen, M is Manganese, and Z- are chloride counterions. To map BMX-001 with instant Formula (BI), R is a C2 alkyl, A is hydrogen, M is Manganese, and Z- are chloride counterions. Reference 2 disclosed in Rajic, teaches porphyrins in the form of their chloride salts.
Regarding Claims 71 and 74, because Rajic teaches the dosage range of BMX-001 as 0.5 to 9 mg/kg/day, and 1 mg/kg activity equivalent of BMX-001 would be 0.5 to 9 mg/kg/day of an active agent, the porphyrin disclosed in Moeller, MnTE-2 PyP5+, administered at 6 mg/kg falls within the range of the activity equivalent of BMX-001. The courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05-II. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding Claims 71-75, 78, 83-85, 86, 87, and 89, It would have been prima facie obvious, for one of ordinary skill before the effective filing date to take the method disclosed in Rabbani for treating breast carcinomas in mice caused by oxidative stress with MnTE-2 PyP5+ , and combine it with the method disclosed in Moeller for administering MnTE-2 PyP5+ to enhance tumor radio responsiveness caused by oxidative stress and the toxicity study disclosed in Rajic for BMX-001, to arrive at the claimed limitations because Rabbani, Moeller, and Rajic all teach Mn porphyrins administered to treat oxidative stress. It would be obvious to administer the same class of compounds (Mn porphyrins), to treat the same biological mechanism/process (oxidative stress related diseases), get expected results.
Regarding Claim 82, The courts noted that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Claim 82 is dependent from Claim 71, but does not recite any additional method steps, only the intended results of the method of Claim 71. Therefore, if Claim 71 is determined to be obvious over Rabbani and Moeller, Claim 82 is treated the same.
Claims 71-75, 78, 83, 86, 87, 89, and 90 are rejected under 35 U.S.C. 103 as being unpatentable over Spasojevic (Ivan Spasojevic et al., “Pharmacokinetics, Brain Hippocampus and Cortex, and Mitochondrial Accumulation of a New Generation of Lipophilic Redox-Active Therapeutic, Mn(III) Meso Tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin, MnTnBuOE-2-PyP5+, in Comparison with its Ethyl and N-hexyl Analogs, MnTE-2-PyP5+ and MnTnHex-2-PyP5+”, Duke University, Pg. 304, Pub. Date: November 2013) in view of Rajic (Zrinka Rajic et al., “A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity”, Free Radical Biology and Medicine, Volume 52, Issue 9, Pgs. 1828-1834, Pub. Date: May 1, 2012) and Rabbani (Zahid Rabbani et al., “Antiangiogenic action of redox-modulating Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP5+, via suppression of oxidative stress in a mouse model of breast tumor”, Free Radical Biology and Medicine, Volume 47, Issue 7, Pgs. 992-1004, Pub. Date: October 2009).
The teachings of Rabbani and Rajic, as discussed above, with respect to claim 71 are incorporated into this rejection.
Spasojevic teaches MnTnBuOE-2-Pyp5+, herein BMX-001, see below, as a compound for efficacy in models of oxidative stress related diseases such as radiation, and central nervous system injuries. BMX-001 showed efficacy in cancer as sole agents and as radio and chemosensitizers. BMX-001 is less toxic, but equally potent and lipophilic as MnTE-2-Pyp5+, a known meso-substituted porphyrin (Pg. 304).
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Regarding the claim limitation of the loading dose and maintenance dosing, Rabbani discloses “loading dose of MnTE-2-PyP5+ may be necessary for a certain time period, followed by a maintenance dosing. Further studies will optimize the dosing regimen whereby anti-cancer effects may be enhanced.” (Pg. 998). The courts have found that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); Therefore it would be obvious to optimize to optimize the maintenance dose to about 25% to about 75% of the loading dose, because it was already known in the art to administer a maintenance dose that is less than the loading dose. One of ordinary skill could easily optimize the percentage of the maintenance dose, to arrive at the claimed limitations.
It would have been prima facie obvious for one of ordinary skill before the effective filing date, to take the method disclosed in Spasojevic, for administering BMX-001 to treat oxidative stress caused by radiation and central nervous system injuries, and combine it with the method disclosed in Rajic for administering Mn porphyrins for oxidative stress related injuries, and Rabbani for administering Mn porphyrins to treat oxidative stress related diseases and administering maintenance/loading dosing, because all of the methods disclose Mn porphyrins administered therapeutically to treat oxidative stress related diseases. One ordinary skill would be motivated to administer BMX-001 at 0.05 mg/kg following radiation or chemotherapy exposure as in the instant claims, because BMX-001 was known in the prior art to be administered at that concentration, for that purpose.
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.
Claims 71-90 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, and 14 of U.S. Patent No. 12171769.
Regarding instant Claims 71-90, Claims 1, 9, and 14 in U.S. Patent No. 12171769 disclose:
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Although the claims at issue are not identical, they are not patentably distinct from each other because Claims 1, 9, and 14 in U.S. Patent No. 12171769 recite the same treatment method as instant Claims 71-90 are therefore not patentably distinct.
Claims 71-90 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, and 14, of U.S. Patent No. 11285162.
Regarding instant Claims 71-90, Claims 1, 10, and 14 in U.S. Patent No. 11285162 disclose:
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Although the claims at issue are not identical, they are not patentably distinct from each other because Claims 1, 10, and 14 in U.S. Patent No. 11285162 recite the same treatment method and therefore teach all the limitations of instant Claims 71-90.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIERRA M ROCHELLE whose telephone number is (571)272-9962. The examiner can normally be reached Mon-Fri 8:00-5:00 EST.
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/C.M.R./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627
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