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 .
Status of the Claims
Claims 41 – 60 are pending and rejected.
Priority
The present claim 41 is drawn to a method:
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The present claim 45 is drawn to a method of claim 41, wherein the salt thereof is a p-toluenesulfonic acid salt monohydrate of formula (II):
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All of the priority documents provide sufficient support for the compound of formula (I) and (II) and the method of using said compounds. Therefore, the instant claims receive the filing date of the earlier filed priority documents and are now examined with an effective filing date of October 23, 2015 (the filing date of the Provisional ‘632 Application).
Response to Applicant’s Remarks
Applicant’s remarks filed on February 17, 2025 have been fully considered.
The objections to claims 41 and 51 are withdrawn in view of Applicant’s amendments to recite proper punctuations and articles in the claims.
The rejection under 35 U.S.C. §112(a) of claims 41 – 56 and 58 – 60 as not being enabled is withdrawn in view of Applicant’s amendments to limit the scope of cancers and solid tumors that are properly enabled by the specification.
The rejection under 35 U.S.C. §112(a) of claims 41 – 60 as failing to comply with the written description requirement is withdrawn in view of Applicant’s amendments to recite the compound of formulae (I) and (II) that are properly supported by the present specification.
The rejection under 35 U.S.C. §112(b) of claims 42 – 44, 48 – 50, 52 – 54 and 58 – 60 for insufficient antecedent basis is withdrawn in view of Applicant’s amendments to delete the limitation “the daily dose” in the claims.
The rejection under 35 U.S.C. §112(b) of claim 56 for insufficient antecedent basis is withdrawn in view of Applicant’s amendments to replace the limitation “cancer” with “solid tumor” in the claim.
The rejections under 35 U.S.C. §103 of:
claims 41 – 43, 45, 47, 51 – 53 and 55 as being unpatentable over Sugimoto et al. US 2012/0264738 A1,
claims 44, 48 – 50, 54, and 58 – 60 as being unpatentable over Sugimoto et al. US 2012/0264738 A1, as applied to claims 41 – 43, 45, 47, 51 – 53 and 55 above,
claims 46 and 56 – 57 as being unpatentable over Sugimoto et al. US 2012/0264738 A1, as applied to claims 41 – 43, 45, 47, 51 – 53 and 55 above, and in further view of Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40, and
claims 44, 48 – 50, 54, and 58 – 60 as being unpatentable over Sugimoto et al. US 2012/0264738 A1 in view of Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40, as applied to claims 41 – 43, 45 – 47, 51 – 53 and 55 – 57 above,
are withdrawn in view of Applicant’s amendments to recite the amended compound of formula (I), and limit the scope of cancers in the claims.
The rejections on the ground of nonstatutory double patenting of:
claims 41 – 60 as being unpatentable over claims 1 – 38 of U.S. Patent No. 11,058,673 B2 in view of Sugimoto et al. US 2012/0264738 A1,
claims 41 – 60 as being unpatentable over claims 1 – 6, 12, and 15 – 17 of U.S. Patent No. 8,629,133 B2 in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40,
claims 41 – 60 as being unpatentable over claims 1 – 2 of U.S. Patent No. 9,359,368 in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40,
claims 41 – 44, 46 – 54 and 56 – 60 as being unpatentable over claims 1 – 2 of U.S. Patent No. 9,540,386 in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40,
claims 41 – 44, 46 – 54 and 56 – 60 as being unpatentable over claims 1 – 2 of U.S. Patent No. 9,718,830 in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40,
claims 41 – 44, 46 – 54 and 56 – 60 as being unpatentable over claims 1 – 2 of U.S. Patent No. 9,718,831 in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40,
claims 41 – 44, 46 – 54 and 56 – 60 as being unpatentable over claims 1 – 2 of U.S. Patent No. 9,745,315 in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40,
claims 41 – 44, 46 – 54 and 56 – 60 as being unpatentable over claims 1 – 2 of U.S. Patent No. 9,884,871 in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40,
claims 41 – 44, 46 – 54 and 56 – 60 as being unpatentable over claims 1 – 2 of U.S. Patent No. 10,023,578 in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40, and
claims 41 – 44, 46 – 54 and 56 – 60 as being unpatentable over claims 1 – 2 of U.S. Patent No. 10,030,030 in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40,
are withdrawn in view of Applicant’s amendments to recite the amended compound of formula (I), and limit the scope of cancers in the claims.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 21, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 42 – 43 and 52 – 53 are objected to because of the following informalities:
Claim 42, line 1 of the claim: The limitation “wherein is 80 mg + 10% to 250 mg + 10% of the compound” is grammatically improper because it contains an improper placement of the term “is”. In order to overcome the objection, Applicant may amend to the limitation “wherein+ 10% to 250 mg + 10% of the compound” in line 1.
Claim 43, line 1 of the claim: The limitation “wherein is 250 mg + 10% of the compound” is grammatically improper because it contains an improper placement of the term “is”. In order to overcome the objection, Applicant may amend to the limitation “wherein+ 10% of the compound” in line 1.
Claim 52, line 1 of the claim: The limitation “wherein is 80 mg + 10% to 250 mg + 10% of the compound” is grammatically improper because it contains an improper placement of the term “is”. In order to overcome the objection, Applicant may amend to the limitation “wherein+ 10% to 250 mg + 10% of the compound” in line 1.
Claim 53, line 1 of the claim: The limitation “wherein is 250 mg + 10% of the compound” is grammatically improper because it contains an improper placement of the term “is”. In order to overcome the objection, Applicant may amend to the limitation “wherein+ 10% of the compound” in line 1.
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.
Claim 46 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
The instant claim recites the limitation “the solid tumor has amplified MDM2 genes…”. However, claim 41 is drawn to a method of treating a cancer. It does not explicitly recite limitations drawn to “the solid tumor”. Therefore, there is insufficient antecedent basis for this limitation in the claim.
In order to overcome the rejection, Applicant may amend claim 46 to replace the term “solid tumor” with “cancer”. For examination purposes, the limitation is interpreted as “the cancer has amplified MDM2 genes…”.
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.
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.
Claims 41 – 43, 45 – 47, 51 – 53 and 55 – 57 are rejected under 35 U.S.C. 103 as being unpatentable over Sugimoto et al. US 2012/0264738 A1 (publ. October 18, 2012; effect. filed March 10, 2011) in view of Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40 (publ. online November 2012), as disclosed in the IDS filed on November 24, 2021.
Determining the scope and contents of the prior art
Sugimoto et al. teach the compound of Example 198 (see, e.g., paragraphs [1193]-[1194]):
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Sugimoto teaches that the compound can be administered to a human in a dose range preferably from 0.1 to 100 mg/kg. See, e.g., paragraph [0198]. Sugimoto also teaches that the compound can be used to treat human osteosarcoma cell line SJSA-1 or SJSA-1-RE in mice. The compound is orally administered “twice a day (bid) at a dose of 50 mg/kg, once a day (qd) at a dose of 50 mg/kg, or once a day (qd) at a dose of 25 mg/kg for 4 consecutive days”. See, e.g., Test Example 3, paragraph [01841]. Using a standard surface area conversion by the Examiner, the daily dosage amounts are equivalent of 125, 250, and 500 mg in a 60 kg adult.
Ascertaining the differences between the prior art and the claims at issue
The difference is that the compound of Example 198 is a stereoisomer of the compound of formula (I) as instantly claimed. Further, Sugimoto does not explicitly teach that the cancer or solid tumor is specifically soft tissue sarcoma, as claimed in the instant claims and elected by the Applicant.
Rationale for a prima facie case of obviousness
According to MPEP §2141(III), one of the rationales in the KSR decision states “(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Sugimoto et al. does teach the compound of general formula (1):
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(see, e.g., paragraph [0010]).
Sugimoto also teaches that the compound can also have stereoisomers or optical isomers “due to asymmetric carbon atoms”. See, e.g., paragraph [0148]. A person having ordinary skill in the art would have been motivated to perform routine experimentation to test the stereoisomeric isomers of the compound of Example 198 because said compound is identified in Sugimoto as a lead compound. The PHOSITA would have a reasonable expectation that the stereoisomeric isomer of the compound would also successfully treat osteosarcoma in the subject because similar properties would have been expected from structurally similar compounds.
With respect to the difference that Sugimoto et al. do not teach that the cancer or solid tumor is specifically soft tissue sarcoma, it teaches that the compound of general formula (1) has potent MDM2 inhibiting activity. See, e.g., paragraphs [0007]-[0008] and [0078]. Sugimoto further defines “MDM2 inhibitor” as “a factor that restores p53 functions suppressed by Mdm2 by acting on either Mdm2 or p53, or on both Mdm2 and p53… [t]he p53 functions are not particularly limited so long as they are functions that p53 normally has… [e]xamples thereof include inhibition of canceration of cells by inducing the expression of genes involved in the cell cycle or cellular apoptosis”. See, e.g., paragraph [0081]. Sugimoto also teaches that the compound can be used to treat several cancers, including sarcomas. See, e.g., paragraph [0193].
Ray-Coquard et al. teach that “MDM2 is an E3 ligase that binds P53 and regulates P53 protein concentrations through a negative feedback loop in which raised nuclear P53 concentrations activate MDM2 transcription while MDM2 blocks the P53 transactivation domain, targeting P53 for degradation… [i]n cells that overexpress MDM2, P53 is inactivated, leading to inefficient growth arrest and apoptosis… [b]locking the P53–MDM2 interaction might restore P53 function and could be a novel approach to cancer treatment”. See, e.g., pp. 1133, 1st paragraph. Ray-Coquard teaches that MDM2 inhibitors were known to be of interest for the treatment of patients with MDM2-amplified liposarcomas (type of soft tissue sarcoma). See, e.g., Abstract, and pp. 1139, 2nd-4th paragraphs. A person having ordinary skill in the art would have been motivated to treat liposarcoma with amplified MDM2 genes or overexpression of MDM2 with the instantly claimed composition because Sugimoto teaches that the compound of Example 198 has potent MDM2 inhibiting activity and Ray-Coquard teaches that liposarcomas, including those of MDM2 overexpression, are effectively treated using MDM2 inhibitors. The PHOSITA would have performed routine experimentation and combined the teachings of the prior art to optimize the method of treatment. The PHOSITA would have a reasonable expectation that the stereoisomeric and positional isomer of the compound of Example 198 would have treated liposarcoma, that has amplified MDM2 genes in its genome or overexpresses MDM2, in patients successfully.
The prior art would have rendered the instant claims prima facie obvious as presented below:
Claim 41, directed to a method of treating liposarcoma (type of soft tissue sarcoma) in a subject in need thereof, comprising orally administering to the subject a compound of formula (I)
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Claims 42 – 43, wherein 250 mg of the compound, or the salt thereof, is administered to the subject.
Claim 45, wherein the salt is a p-toulenesulfonic acid salt monohydrate of formula (II)
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Claim 46, wherein liposarcoma has amplified MDM2 genes in its genome or overexpresses MDM2.
Claim 47, wherein liposarcoma comprises a wild type TP53 gene.
Claim 51, directed to a method of treating liposarcoma (type of solid tumor) in a subject in need thereof, comprising orally administering to the subject a compound of formula (I)
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Claims 52 – 53, wherein 250 mg of the compound, or the salt thereof, is administered to the subject.
Claim 55, wherein the salt is a p-toulenesulfonic acid salt monohydrate of formula (II)
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Claim 56, wherein liposarcoma has amplified MDM2 genes in its genome or overexpresses MDM2.
Claim 57, wherein liposarcoma comprises a wild type TP53 gene.
Claims 44, 48 – 50, 54, and 58 – 60 are rejected under 35 U.S.C. 103 as being unpatentable over Sugimoto et al. US 2012/0264738 A1 (publ. October 18, 2012; effect. filed March 10, 2011) in view of Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40 (publ. online November 2012), as applied to claims 41 – 43, 45 – 47, 51 – 53 and 55 – 57 above.
Determining the scope and contents of the prior art
Sugimoto et al. teach the compound of Example 198 (see, e.g., paragraphs [1193]-[1194]):
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Sugimoto teaches that the compound can be administered to a human in a dose range preferably from 0.1 to 100 mg/kg. See, e.g., paragraph [0198]. Sugimoto also teaches that the compound can be used to treat human osteosarcoma cell line SJSA-1 or SJSA-1-RE in mice. The compound is orally administered “twice a day (bid) at a dose of 50 mg/kg, once a day (qd) at a dose of 50 mg/kg, or once a day (qd) at a dose of 25 mg/kg for 4 consecutive days”. See, e.g., Test Example 3, paragraph [01841]. Using a standard surface area conversion by the Examiner, the daily dosage amounts are equivalent of 125, 250, and 500 mg in a 60 kg adult.
Ascertaining the differences between the prior art and the claims at issue
The difference is that the compound of Example 198 is a stereoisomer of the compound of formula (I) as instantly claimed. Further, Sugimoto does not explicitly teach that the cancer or solid tumor is specifically soft tissue sarcoma, as claimed in the instant claims and elected by the Applicant. Additionally, Sugimoto does not explicitly teach that 130, 160, 200 and 260 mg of the compound is administered to the subject, as claimed in the instant claims 44, 48 – 50, 54, and 58 – 60.
Rationale for a prima facie case of obviousness
According to MPEP §2141(III), one of the rationales in the KSR decision states “(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Sugimoto et al. does teach the compound of general formula (1):
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(see, e.g., paragraph [0010]).
Sugimoto also teaches that the compound can also have stereoisomers or optical isomers “due to asymmetric carbon atoms”. See, e.g., paragraph [0148]. A person having ordinary skill in the art would have been motivated to perform routine experimentation to test the stereoisomeric isomers of the compound of Example 198 because said compound is identified in Sugimoto as a lead compound. The PHOSITA would have a reasonable expectation that the stereoisomeric isomer of the compound would also successfully treat osteosarcoma in the subject because similar properties would have been expected from structurally similar compounds.
With respect to the difference that Sugimoto et al. do not teach that the cancer or solid tumor is specifically soft tissue sarcoma, it teaches that the compound of general formula (1) has potent MDM2 inhibiting activity. See, e.g., paragraphs [0007]-[0008] and [0078]. Sugimoto further defines “MDM2 inhibitor” as “a factor that restores p53 functions suppressed by Mdm2 by acting on either Mdm2 or p53, or on both Mdm2 and p53… [t]he p53 functions are not particularly limited so long as they are functions that p53 normally has… [e]xamples thereof include inhibition of canceration of cells by inducing the expression of genes involved in the cell cycle or cellular apoptosis”. See, e.g., paragraph [0081]. Sugimoto also teaches that the compound can be used to treat several cancers, including sarcomas. See, e.g., paragraph [0193].
Ray-Coquard et al. teach that “MDM2 is an E3 ligase that binds P53 and regulates P53 protein concentrations through a negative feedback loop in which raised nuclear P53 concentrations activate MDM2 transcription while MDM2 blocks the P53 transactivation domain, targeting P53 for degradation… [i]n cells that overexpress MDM2, P53 is inactivated, leading to inefficient growth arrest and apoptosis… [b]locking the P53–MDM2 interaction might restore P53 function and could be a novel approach to cancer treatment”. See, e.g., pp. 1133, 1st paragraph. Ray-Coquard teaches that MDM2 inhibitors were known to be of interest for the treatment of patients with MDM2-amplified liposarcomas (type of soft tissue sarcoma). See, e.g., Abstract, and pp. 1139, 2nd-4th paragraphs. A person having ordinary skill in the art would have been motivated to treat liposarcoma with amplified MDM2 genes or overexpression of MDM2 with the instantly claimed composition because Sugimoto teaches that the compound of Example 198 has potent MDM2 inhibiting activity and Ray-Coquard teaches that liposarcomas, including those of MDM2 overexpression, are effectively treated using MDM2 inhibitors. The PHOSITA would have performed routine experimentation and combined the teachings of the prior art to optimize the method of treatment. The PHOSITA would have a reasonable expectation that the stereoisomeric and positional isomer of the compound of Example 198 would have treated liposarcoma, that has amplified MDM2 genes in its genome or overexpresses MDM2, in patients successfully.
With respect to the differences in the doses claimed in instant claims 44, 48 – 50, 54, and 58 – 60, MPEP §2144.05(I) states “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)”. Further, MPEP §2144.05(II)(A) states:
“Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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 re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
In the instant case, Sugimoto teaches that the compound can be administered to a human in a dose range preferably from 0.1 to 100 mg/kg and also teaches preferably daily dosages of “twice a day (bid) at a dose of 50 mg/kg, once a day (qd) at a dose of 50 mg/kg, or once a day (qd) at a dose of 25 mg/kg” . See, e.g., paragraphs [0198] and [01841]. The range disclosed by Sugimoto et al. completely encompasses the claimed daily doses of the compound is 130, 160, 200 and 260 mg of the compound of Example 198. A PHOSITA would expect that the concentration of the compound within the range would be a good starting point to perform routine experimentation and determine which concentration of the compound within the pharmaceutical composition would be sufficient in order to optimize and enhance the pharmaceutical properties of the compound.
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 41 – 60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 38 of U.S. Patent No. 11,058,673 B2 (US ‘673) in view of Sugimoto et al. US 2012/0264738 A1. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 in US ‘673 claims a method
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Claims 2 – 8 in US ‘673 specifically claim the method
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With respect to the instant claims, the claims in US ‘673 do not explicitly claim the specific doses of said compound in the instant claims.
According to MPEP §2141(III), one of the rationales in the KSR decision states “(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Sugimoto et al. teach the compound of general formula (1):
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(see, e.g., paragraph [0010]).
Sugimoto et al. also teach that the compound can also have stereoisomers or optical isomers “due to asymmetric carbon atoms”. See, e.g., paragraph [0148]. Further, Sugimoto et al. teach the compound of Example 198 (see, e.g., paragraphs [1193]-[1194]):
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Sugimoto teaches that the compound can be administered to a human in a dose range preferably from 0.1 to 100 mg/kg. See, e.g., paragraph [0198]. Sugimoto also teaches that the compound can be used to treat human osteosarcoma cell line SJSA-1 or SJSA-1-RE in mice. The compound is orally administered “twice a day (bid) at a dose of 50 mg/kg, once a day (qd) at a dose of 50 mg/kg, or once a day (qd) at a dose of 25 mg/kg for 4 consecutive days”. See, e.g., Test Example 3, paragraph [01841]. Using a standard surface area conversion by the Examiner, the daily dosage amounts are equivalent of 125, 250, and 500 mg in a 60 kg adult.
A person having ordinary skill in the art would have been motivated to perform routine experimentation to test the stereoisomeric isomers of the compound of Example 198 because said compound is identified in Sugimoto as a lead compound. The PHOSITA would have a reasonable expectation that the stereoisomeric isomer of the compound would also successfully treat liposarcoma in the subject because similar properties would have been expected from structurally similar compounds.
Therefore, the claims in US ‘673 render the instant claims unpatentable for obviousness-type double patenting.
Claims 41 – 60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 6, 12, and 15 – 17 of U.S. Patent No. 8,629,133 B2 (US ‘133) in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 in US ‘133 claims a compound represented by general formula (1) or a salt thereof:
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Claim 12 in US ‘133 specifically claim the compound:
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MPEP §804(II)(B)(1)(2nd paragraph) states:
“Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970).”
For example, the specification of US ‘133 teaches the method for treating cancer, comprising administering said compound. The cancer can be selected from lung cancer, breast cancer, prostate cancer, colon cancer, acute myeloid leukemia, malignant lymphoma, malignant melanoma, retinoblastoma, neuroblastoma, and sarcoma. See, e.g., column 10, lines 8-12.
With respect to the instant claims, the claims in US ‘133 do not explicitly claim the specific doses of said compound in the instant claims and specifically treating soft tissue sarcoma.
According to MPEP §2141(III), one of the rationales in the KSR decision states “(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Sugimoto et al. teach the compound of general formula (1):
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(see, e.g., paragraph [0010]).
Sugimoto et al. also teach that the compound can also have stereoisomers or optical isomers “due to asymmetric carbon atoms”. See, e.g., paragraph [0148]. Sugimoto et al. teach the compound of Example 198 (see, e.g., paragraphs [1193]-[1194]):
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Sugimoto teaches that the compound can be administered to a human in a dose range preferably from 0.1 to 100 mg/kg. See, e.g., paragraph [0198]. Sugimoto also teaches that the compound can be used to treat human osteosarcoma cell line SJSA-1 or SJSA-1-RE in mice. The compound is orally administered “twice a day (bid) at a dose of 50 mg/kg, once a day (qd) at a dose of 50 mg/kg, or once a day (qd) at a dose of 25 mg/kg for 4 consecutive days”. See, e.g., Test Example 3, paragraph [01841]. Using a standard surface area conversion by the Examiner, the daily dosage amounts are equivalent of 125, 250, and 500 mg in a 60 kg adult.
A person having ordinary skill in the art would have been motivated to perform routine experimentation to test the stereoisomeric isomers of the compound of Example 198 because said compound is identified in Sugimoto as a lead compound. The PHOSITA would have a reasonable expectation that the stereoisomeric isomer of the compound would also successfully treat liposarcoma in the subject because similar properties would have been expected from structurally similar compounds.
With respect to the difference that the claims in US ‘133 do not teach that the cancer or solid tumor is specifically soft tissue sarcoma, Sugimoto does teach that the compound of general formula (1) has potent MDM2 inhibiting activity. See, e.g., paragraphs [0007]-[0008] and [0078]. Sugimoto further defines “MDM2 inhibitor” as “a factor that restores p53 functions suppressed by Mdm2 by acting on either Mdm2 or p53, or on both Mdm2 and p53… [t]he p53 functions are not particularly limited so long as they are functions that p53 normally has… [e]xamples thereof include inhibition of canceration of cells by inducing the expression of genes involved in the cell cycle or cellular apoptosis”. See, e.g., paragraph [0081]. Sugimoto also teaches that the compound can be used to treat several cancers, including sarcomas. See, e.g., paragraph [0193].
Ray-Coquard et al. teach that “MDM2 is an E3 ligase that binds P53 and regulates P53 protein concentrations through a negative feedback loop in which raised nuclear P53 concentrations activate MDM2 transcription while MDM2 blocks the P53 transactivation domain, targeting P53 for degradation… [i]n cells that overexpress MDM2, P53 is inactivated, leading to inefficient growth arrest and apoptosis… [b]locking the P53–MDM2 interaction might restore P53 function and could be a novel approach to cancer treatment”. See, e.g., pp. 1133, 1st paragraph. Ray-Coquard teaches that MDM2 inhibitors were known to be of interest for the treatment of patients with MDM2-amplified liposarcomas (type of soft tissue sarcoma). See, e.g., Abstract, and pp. 1139, 2nd-4th paragraphs. A person having ordinary skill in the art would have been motivated to treat liposarcoma with amplified MDM2 genes or overexpression of MDM2 with the instantly claimed composition because Sugimoto teaches that the compound of Example 198 has potent MDM2 inhibiting activity and Ray-Coquard teaches that liposarcomas, including those of MDM2 overexpression, are effectively treated using MDM2 inhibitors. The PHOSITA would have performed routine experimentation and combined the teachings of the prior art to optimize the method of treatment. The PHOSITA would have a reasonable expectation that the stereoisomeric isomer of the compound of Example 198 would have treated liposarcoma, that has amplified MDM2 genes in its genome or overexpresses MDM2, in patients successfully.
Therefore, the claims in US ‘133 render the instant claims unpatentable for obviousness-type double patenting.
Claims 41 – 60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2 of U.S. Patent No. 9,359,368 (US ‘368) in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 in US ‘368 claims a crystal of the compound represented by formula (1) or a salt thereof:
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MPEP §804(II)(B)(1)(2nd paragraph) states:
“Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970).”
For example, the specification of US ‘368 teaches that the crystal of said compound can be used for the treatment of tumors or cancers selected preferably from lung cancer, breast cancer, prostate cancer, colon cancer, acute myeloid leukemia, malignant lymphoma, malignant melanoma, retinoblastoma, neuroblastoma, and sarcoma. See, e.g., column 10, lines 31-34.
With respect to the instant claims, the claims in US ‘368 do not explicitly claim the specific doses of said compound in the instant claims and specifically treating soft tissue sarcoma.
According to MPEP §2141(III), one of the rationales in the KSR decision states “(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Sugimoto et al. teach the compound of general formula (1):
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(see, e.g., paragraph [0010]).
Sugimoto et al. also teach that the compound can also have stereoisomers or optical isomers “due to asymmetric carbon atoms”. See, e.g., paragraph [0148]. Sugimoto et al. teach the compound of Example 198 (see, e.g., paragraphs [1193]-[1194]):
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Sugimoto teaches that the compound can be administered to a human in a dose range preferably from 0.1 to 100 mg/kg. See, e.g., paragraph [0198]. Sugimoto also teaches that the compound can be used to treat human osteosarcoma cell line SJSA-1 or SJSA-1-RE in mice. The compound is orally administered “twice a day (bid) at a dose of 50 mg/kg, once a day (qd) at a dose of 50 mg/kg, or once a day (qd) at a dose of 25 mg/kg for 4 consecutive days”. See, e.g., Test Example 3, paragraph [01841]. Using a standard surface area conversion by the Examiner, the daily dosage amounts are equivalent of 125, 250, and 500 mg in a 60 kg adult.
A person having ordinary skill in the art would have been motivated to perform routine experimentation to test the stereoisomeric isomers of the compound of Example 198 because said compound is identified in Sugimoto as a lead compound. The PHOSITA would have a reasonable expectation that the stereoisomeric isomer of the compound would also successfully treat liposarcoma in the subject because similar properties would have been expected from structurally similar compounds.
With respect to the difference that the claims in US ‘133 do not teach that the cancer or solid tumor is specifically soft tissue sarcoma, Sugimoto does teach that the compound of general formula (1) has potent MDM2 inhibiting activity. See, e.g., paragraphs [0007]-[0008] and [0078]. Sugimoto further defines “MDM2 inhibitor” as “a factor that restores p53 functions suppressed by Mdm2 by acting on either Mdm2 or p53, or on both Mdm2 and p53… [t]he p53 functions are not particularly limited so long as they are functions that p53 normally has… [e]xamples thereof include inhibition of canceration of cells by inducing the expression of genes involved in the cell cycle or cellular apoptosis”. See, e.g., paragraph [0081]. Sugimoto also teaches that the compound can be used to treat several cancers, including sarcomas. See, e.g., paragraph [0193].
Ray-Coquard et al. teach that “MDM2 is an E3 ligase that binds P53 and regulates P53 protein concentrations through a negative feedback loop in which raised nuclear P53 concentrations activate MDM2 transcription while MDM2 blocks the P53 transactivation domain, targeting P53 for degradation… [i]n cells that overexpress MDM2, P53 is inactivated, leading to inefficient growth arrest and apoptosis… [b]locking the P53–MDM2 interaction might restore P53 function and could be a novel approach to cancer treatment”. See, e.g., pp. 1133, 1st paragraph. Ray-Coquard teaches that MDM2 inhibitors were known to be of interest for the treatment of patients with MDM2-amplified liposarcomas (type of soft tissue sarcoma). See, e.g., Abstract, and pp. 1139, 2nd-4th paragraphs. A person having ordinary skill in the art would have been motivated to treat liposarcoma with amplified MDM2 genes or overexpression of MDM2 with the instantly claimed composition because Sugimoto teaches that the compound of Example 198 has potent MDM2 inhibiting activity and Ray-Coquard teaches that liposarcomas, including those of MDM2 overexpression, are effectively treated using MDM2 inhibitors. The PHOSITA would have performed routine experimentation and combined the teachings of the prior art to optimize the method of treatment. The PHOSITA would have a reasonable expectation that the stereoisomeric isomer of the compound of Example 198 would have treated liposarcoma, that has amplified MDM2 genes in its genome or overexpresses MDM2, in patients successfully.
Therefore, the claims in US ‘368 render the instant claims unpatentable for obviousness-type double patenting.
Claims 41 – 44, 46 – 54 and 56 – 60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2 of U.S. Patent No. 9,540,386 (US ‘386) in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 in US ‘386 claims a crystal of the compound represented by formula (1) or a salt thereof:
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428
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MPEP §804(II)(B)(1)(2nd paragraph) states:
“Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970).”
For example, the specification of US ‘386 teaches that the crystal of said compound can be used for the treatment of tumors or cancers selected preferably from lung cancer, breast cancer, prostate cancer, colon cancer, acute myeloid leukemia, malignant lymphoma, malignant melanoma, retinoblastoma, neuroblastoma, and sarcoma. See, e.g., column 10, lines 31-34.
With respect to the instant claims, the claims in US ‘386 do not explicitly claim the specific doses of said compound in the instant claims and specifically treating soft tissue sarcoma.
According to MPEP §2141(III), one of the rationales in the KSR decision states “(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Sugimoto et al. teach the compound of general formula (1):
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(see, e.g., paragraph [0010]).
Sugimoto et al. also teach that the compound can also have stereoisomers or optical isomers “due to asymmetric carbon atoms”. See, e.g., paragraph [0148]. Sugimoto et al. teach the compound of Example 198 (see, e.g., paragraphs [1193]-[1194]):
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260
478
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Greyscale
Sugimoto teaches that the compound can be administered to a human in a dose range preferably from 0.1 to 100 mg/kg. See, e.g., paragraph [0198]. Sugimoto also teaches that the compound can be used to treat human osteosarcoma cell line SJSA-1 or SJSA-1-RE in mice. The compound is orally administered “twice a day (bid) at a dose of 50 mg/kg, once a day (qd) at a dose of 50 mg/kg, or once a day (qd) at a dose of 25 mg/kg for 4 consecutive days”. See, e.g., Test Example 3, paragraph [01841]. Using a standard surface area conversion by the Examiner, the daily dosage amounts are equivalent of 125, 250, and 500 mg in a 60 kg adult.
A person having ordinary skill in the art would have been motivated to perform routine experimentation to test the stereoisomeric isomers of the compound of Example 198 because said compound is identified in Sugimoto as a lead compound. The PHOSITA would have a reasonable expectation that the stereoisomeric isomer of the compound would also successfully treat liposarcoma in the subject because similar properties would have been expected from structurally similar compounds.
With respect to the difference that the claims in US ‘386 do not teach that the cancer or solid tumor is specifically soft tissue sarcoma, Sugimoto does teach that the compound of general formula (1) has potent MDM2 inhibiting activity. See, e.g., paragraphs [0007]-[0008] and [0078]. Sugimoto further defines “MDM2 inhibitor” as “a factor that restores p53 functions suppressed by Mdm2 by acting on either Mdm2 or p53, or on both Mdm2 and p53… [t]he p53 functions are not particularly limited so long as they are functions that p53 normally has… [e]xamples thereof include inhibition of canceration of cells by inducing the expression of genes involved in the cell cycle or cellular apoptosis”. See, e.g., paragraph [0081]. Sugimoto also teaches that the compound can be used to treat several cancers, including sarcomas. See, e.g., paragraph [0193].
Ray-Coquard et al. teach that “MDM2 is an E3 ligase that binds P53 and regulates P53 protein concentrations through a negative feedback loop in which raised nuclear P53 concentrations activate MDM2 transcription while MDM2 blocks the P53 transactivation domain, targeting P53 for degradation… [i]n cells that overexpress MDM2, P53 is inactivated, leading to inefficient growth arrest and apoptosis… [b]locking the P53–MDM2 interaction might restore P53 function and could be a novel approach to cancer treatment”. See, e.g., pp. 1133, 1st paragraph. Ray-Coquard teaches that MDM2 inhibitors were known to be of interest for the treatment of patients with MDM2-amplified liposarcomas (type of soft tissue sarcoma). See, e.g., Abstract, and pp. 1139, 2nd-4th paragraphs. A person having ordinary skill in the art would have been motivated to treat liposarcoma with amplified MDM2 genes or overexpression of MDM2 with the instantly claimed composition because Sugimoto teaches that the compound of Example 198 has potent MDM2 inhibiting activity and Ray-Coquard teaches that liposarcomas, including those of MDM2 overexpression, are effectively treated using MDM2 inhibitors. The PHOSITA would have performed routine experimentation and combined the teachings of the prior art to optimize the method of treatment. The PHOSITA would have a reasonable expectation that the stereoisomeric isomer of the compound of Example 198 would have treated liposarcoma, that has amplified MDM2 genes in its genome or overexpresses MDM2, in patients successfully.
Therefore, the claims in US ‘386 render the instant claims unpatentable for obviousness-type double patenting.
Claims 41 – 44, 46 – 54 and 56 – 60 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 2 of U.S. Patent No. 9,718,830 (US ‘830) in view of Sugimoto et al. US 2012/0264738 A1 and Ray-Coquard et al., Lancet Oncol 2012; 13: 1133–40. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 1 in US ‘830 claims a crystal of the compound represented by formula (1) or a salt thereof:
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MPEP §804(II)(B)(1)(2nd paragraph) states:
“Further, those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970).”
For example, the specification of US ‘830 teaches that the crystal of said compound can be used for the treatment of tumors or cancers selected preferably from lung cancer, breast cancer, prostate cancer, colon cancer, acute myeloid leukemia, malignant lymphoma, malignant melanoma, retinoblastoma, neuroblastoma, and sarcoma. See, e.g., column 10, lines 31-34.
With respect to the instant claims, the claims in US ‘830 do not explicitly claim the specific doses of said compound in the instant claims and specifically treating soft tissue sarcoma.
According to MPEP §2141(III), one of the rationales in the KSR decision states “(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention”. KSR, 550 U.S. at 418, 82 USPQ2d at 1396. Sugimoto et al. teach the compound of general formula (1):
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(see, e.g., paragraph [0010]).
Sugimoto et al. also teach that the compound can also have stereoisomers or optical isomers “due to asymmetric carbon atoms”. See, e.g., paragraph [0148]. Further, Sugimoto et al. teach the compound of Example 198 (see, e.g., paragraphs [1193]-[1194]):
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260
478
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Greyscale
Sugimoto teaches that the compound can be administered to a human in a dose range preferably from 0.1 to 100 mg/kg. See, e.g., paragraph [0198]. Sugimoto also teaches that the compound can be used to treat human osteosarcoma cell line SJSA-1 or SJSA-1-RE in mice. The compound is orally administered “twice a day (bid) at a dose of 50 mg/kg, once a day (qd) at a dose of 50 mg/kg, or once a day (qd) at a dose of 25 mg/kg for 4 consecutive days”. See, e.g., Test Example 3, paragraph [01841]. Using a standard surface area conversion by the Examiner, the daily dosage amounts are equivalent of 125, 250, and 500 mg in a 60 kg adult.
A person having ordinary skill in the art would ha