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 .
Priority
This application is a 371 of PCT/KR2021/019583 (12/22/2021)
and claims foreign priority to KOREA, REPUBLIC OF 10-2020-0180807 (12/22/2020).
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 1-16 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.
Claim 1 reads “A crystalline form I of a compound of the following formula 1, a pharmaceutically acceptable salt thereof, or a solvate thereof, wherein the X-ray powder diffraction (XRPD) pattern has 3 or more characteristic peaks selected from among …” with a list of 2-theta values and “wherein R1 is C2-C5 alkyl”. The 2-theta values are derived from the XRPD of Fig. 1 which the specification states is of Example 1 (Specification p. 29):
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Thus, the 2-theta values only correspond to Example 1 which is not a salt or solvate thereof and only has R1 is isopropyl. As a result, one of skill in the art would find the claim confusing as to how multiple different compounds, salts, and solvates can all share the same XRPD peaks as per claim 1. For example, it is known in the art that small changes in structure cause large changes in XRPD 2-theta values as evidenced by Sivaramakrishna et al. (J. Chem. Sci. Vol. 127, No. 9, September 2015, pp. 1627–1635) in Figure 4 and Table 3 (p. 1633) which shows how the XRPD changes with the alkyl chain length “n”. Similarly, one of skill in the art would know that the different claim 1 R1 alkyl chains of varying length would result in different XRPD 2-theta peaks. Therefore, one of skill in the art would be uncertain as to what are the precise metes and bounds of the claims and the claim is indefinite.
As with claim 1, claims 2-4 are to a scope of R1, salts, and solvates such that the scope of the claims are unclear with respect to the 2-theta values. Claims 2-16 which depend from claim 1 are also rejected as indefinite as they incorporate and do not resolve claim 1’s indefiniteness.
Claims 11, and 14-16 are to a pharmaceutical composition comprising the crystalline form I and a carrier where the specification defines carrier as including solvents such as water, alcohols, ethers, oils, etc. which when combined with the crystalline form necessarily dissolves the form and the “composition” would be only the solution. One of skill in the art would find such claim language confusing as to whether the solution is being claims or only compositions where the crystalline form I is maintained. Thus, the claims are indefinite. For purposes of examination, the claims are interpreted as where the crystal form is not dissolved in a solution.
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 1-4, 11, 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Choi et al. (US20090298829).
Regarding claims 1-3, Choi teaches compounds that are agonists of melanocortin receptor (Title, Abstract, claim 1). Choi teaches Example A96 (Table 4, Table 18, claim 14):
N-[(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidine-3-yl]carbonyl}-5-(morpholine-4-ylcarbonyl)pyrrolidine-3-yl]-N-(4,4-dimethylcyclohexyl)acetamide
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and Example A7 ([0383], Table 18, claim 14):
(4S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-methylpyrrolidine-3-yl]carbonyl}-4-[(2,2-dimethylpropanoyl)(cis-4-methylcyclohexyl)amino]-L-prolineamide
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Choi teaches the compounds are active in the experimental assay reported in Table 18 with EC50 values in the nM range ([0841]-[0848]).
Instant claims formula 1 includes the species of claim 3 having the following structure:
N-[(3S,5S)-1-[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidine-3-carbonyl]-5-(morpholine-4-carbonyl)pyrrolidin-3-yl]-N-(4-methylcyclohexyl)isobutyramide
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Thus, claim 1’s compound differs from Choi’s A96 by a methyl group on the cyclohexyl ring and the alkyl homolog (methyl vs. isopropyl).
One of ordinary skill in the art following the teaching of Choi would have considered other compounds within Choi’s genus (claim 1) including the specific modifications of replacing the 4,4-dimethylcyclohexyl with a 4-methylcyclohexyl in view of the reported success with Choi’s Example A7 having the group. One of ordinary skill in the art would have also recognized that alkyl homologs including methyl and isopropyl could be interchanged and maintain activity in view of A7’s homologous alkyl – MPEP 2144.09. One of ordinary skill in the art would have had a reasonable expectation of success because Choi teaches the genus encompassing the instant claims and because Choi teaches the structurally similar compounds as demonstrating activity.
Regarding the crystalline form I language of the instant claims, Choi teaches preparation of the compound in the same manner as in the instant application but does not disclose the XRPD data. However, such properties are inherent in the product and are inseparable as stated in MPEP 2112.01:
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
…
“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
In this case, the structure of the modified product is identical to the instant claims and is produced in a substantially identical process. Thus, a prima facie case of obviousness has been established and the claim rejected.
Regarding claims 4, 11, 14-16, Choi teaches A7 as an HCl salt and also claims pharmaceutically acceptable salts together with a pharmaceutically acceptable carrier (claims 14-15) which one of ordinary skill in the art would consider in formulating the pharmaceutical as is routinely done in the art and arrive at the claimed invention.
Regarding claim 12-13 to a method of agonizing the function of melanocortin-4 receptor, Choi teaches the same utility (title, abstract, claims 16-19), including for obesity such that one of ordinary skill in the art would have used the compound in the same manner and arrive at the claimed invention.
Claims 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Choi et al. (US20090298829) in view of Carlson et al. (US20030124028), Gardner et al. (Computers and Chemical Engineering 28 (2004) 943–953).
Choi teaches as in the 35 USC 103 rejection supra and incorporated herein. Choi does not specifically teach a crystal form or specific methods of making a crystal form.
Carlson teaches well-known systems for automated high-throughput preparation and screening of salts and polymorphs of drug candidates (emphasis added):
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(Carlson Abstract). Carlson’s system specifically screens for polymorphs using a variety of techniques and solvents including water, methanol, acetonitrile, MTBE, ethylene glycol, THF, and DMSO (claim 1, [0019], [0143]-[0144], [0157]-[0177], Fig. 29)
Carlson’s system is similar to commercially available systems such as CRYSTALMAX as discussed by Gardner (Gardner p. 947-949 “6.”, Figs. 4 and 5 describing CRYSTALMAX) including Gardner’s demonstrated success with salt forms of sulfathiazole (p. 950 “6.1.3”, Fig. 10) and polymorphic forms of Ritonavir (Gardner p. 949 “6.1.1”). Given the high level of skill in the art as evidenced by Choi, Carlson and Gardner, one of ordinary skill in the art would have considered the application of Carlson’s technique using a commercially available system (such as Gardner’s) on Choi’s compound as “routine optimization” because it was well-known, commercially available, and was a routine part of drug discovery (Gardner p. 944-45, Figs. 2-3).
One of ordinary skill in the art would have had a reasonable expectation of success in producing the solid forms of Choi’s modified compound because Carlson and Gardner teach successful application to pharmaceuticals using the well-known and technique (Carlson [0091], [0110], [0124]-[0126]) including particular solvents and conditions (Carlson [0163]-[0165], [0261], Fig. 29), varying temperatures (Carlson [0026], [0138]-[0150], claims 43, 55-56), and seeding (Carlson [0141]). These conditions correspond to the same process as disclosed in in the instant specification.
As in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007) (“When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103.”), one of ordinary skill in the art would have known about the need to select the optimal form of the drug identified by Choi, including the specific salt and polymorphic forms which were known to be predictably discoverable by application of Carlson’s technique and was also within one of ordinary skill in the art’s technical grasp as evidenced by the commercially available system taught by Gardner. Thus, it would have been obvious to try and one of ordinary skill in the art would have anticipated success in the endeavor.
At the time of invention, there was an art recognized need to identify the optimal solid form of a pharmaceutical as established by Carlson, and Gardner (Carlson [0004]-[0005], [0010]-[0011]; Gardner Fig. 2, Fig. 5, p. 944-946, “3.1”, “3.2”, “3.3”). The commercially available automated system that identifies “substantially every polymorph” evidenced by Carlson and Gardner provided a predictable solution to the problem of pharmaceutical solid forms. One of ordinary skill in the art would have pursued the commercially available system with a reasonable expectation of success because the systems were known to identify “substantially every polymorph” (Carlson Abstract) and Gardner demonstrated success with the commercial system (Gardner p. 947-950 “6.”, “6.1.1”, “6.1.3”, Figs. 4 and 5 describing CRYSTALMAX). Similarly, one of ordinary skill in the art would have applied the known technique of pharmaceutical solid form optimization (Carlson; Gardner) to the known product of Choi that would have yielded the predictable result of the optimal pharmaceutical solid form. Alternatively, one of ordinary skill in the art would have used the known technique that successfully identified the optimal solid form of other pharmaceuticals demonstrated by Gardner (sulfathiazole p. 950 “6.1.3”, Fig. 10; Ritonavir p. 949 “6.1.1”) and applied the known optimization technique in the same way to Choi’s compound where the result would have been predictable due to the explicit teaching of Carlson that the techniques was known to identify “substantially every polymorph”.
With each of the claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art in the same field of endeavor. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed with a reasonable expectation of success.
Therefore, the claims are rejected as prima facie obvious.
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 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 7879852 in view of Choi et al. (US20090298829), Carlson et al. (US20030124028), Gardner et al. (Computers and Chemical Engineering 28 (2004) 943–953). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims the same species as Choi and are obvious for the same reasons provided in the 35 USC 103 rejection supra.
Claims 1-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of the following copending Application Nos. (reference applications) in view of Choi et al. (US20090298829), Carlson et al. (US20030124028), Gardner et al. (Computers and Chemical Engineering 28 (2004) 943–953). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference applications claim the same species as the instant claims and are obvious for the same reasons provided in the 35 USC 103 rejection supra.
Reference applications:
17619893
18251101
18251084
18251129
18251111
18258705
18258717
18258730
18558142
18557866
18558148
18558351
18558812
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626