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/US2022/022895 (03/31/2022)
PCT/US2022/022895 has PRO 63/170,226 (04/02/2021).
Claim Rejections - 35 USC § 102
Claims 1-2, 5-7, 45-54 are rejected under 35 U.S.C. 102(a)(1) and (2) as being anticipated by Efremov et al. (WO2020190754, publication date 2020-09-24).
Efremov teaches (p. 403-407) Example 139: “General Procedure C for the preparation of (S)-12-fluoro-4-(1-methyl-1H-pyrazol-5-yl)-7a,8,13,14-tetrahydro-7H-[1,2,4]triazolo[4′,3′:1,6]pyrido[3,2-b]benzofuro[4,3-fg][1,4]oxazonine
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”.
Efremov teaches the compound was obtained as a solid ([1197]: “(S)-12-fluoro-4-(1-methyl-1H-pyrazol-5-yl)-7a,8,13,14-tetrahydro-7H-[1,2,4]triazolo[4′,3′:1,6]pyrido[3,2-b]benzofuro[4,3-fg][1,4]oxazonine was obtained as white solid.”) and crystal ([1198]: (S)-12-fluoro-4-(1-methyl-1H-pyrazol-5-yl)-7a,8,13,14-tetrahydro-7H-[1,2,4]triazolo[4′,3′:1,6]pyrido[3,2-b]benzofuro[4,3-fg][1,4]oxazonine (29.1 g, 59.2 mmol, 99.4% purity, MsOH) was obtained as yellow crystal.).
Regarding the crystalline form and characterized by language of the instant claims, Efremov 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, Efremov teaches the same compound in a solid form. This compound has the identical structure as that of the instant claims. All solid forms possess an inherent X-ray diffraction pattern that only depends upon the manner in which the molecules are packed together. Similarly, all solid forms possess inherent DSC curves and an IR absorption spectrum that depends on a variety of factors beyond how the molecules are packed together. The instantly claimed product is characterized by X-ray powder diffraction pattern data, DSC curve data, and IR data. Said data is inherent properties of the solid form.
The solid form disclosed by the prior art also possesses the inherent properties recited in the instant claims. The prior art compound and that in the instant claims are presumed to be the same compound because they have the same structure and chemical formula. The presumption allows a reasonable inference that they have identical inherent properties.
The discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer. Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999); see MPEP 2112. Thus, the claiming of an unknown property inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). Further, “the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product." Id. See also In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990) (“[W]hen the PTO shows 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.”)
For the reasons identified above, the Examiner has shown a sound basis for believing that the products of the applicant and the prior art are the same, and met the burden of proving a prima facie case of anticipation by inherency. The burden properly shifts to Applicants to prove that the prior art solid and the instantly claimed solid are not the same.
Regarding claims 45-49 and 53 to a pharmaceutical composition, Efremov teaches the same pharmaceutical composition (claim 32). Regarding claims 50-52 and 54 to a drug substance, this is construed as reading on the compound itself.
Thus, the claims are anticipated.
Response to Remarks - 35 USC § 102
Applicant argues that Efremov’s Example 139 product is a mesylate salt and not a free-base as claimed. Applicant also argues that the Efremov’s Example 139 intermediate “while a free-base of the claimed compound” is characterized as a white solid with no description of a crystalline solid form.
This is not persuasive because Efremov does teach the same compound in a solid form and as per MPEP 2112 (There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)), the crystalline form need not be recognized in the prior art to anticipate.
Claim Rejections - 35 USC § 103
When the reference discloses all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention but has basis for shifting the burden of proof to applicant as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980). See MPEP §§ 2112 - 2112.02.
In the alternative, claims 1-2, 5-7, 45-54 are rejected under 35 U.S.C. 103 as being unpatentable over Efremov et al. (WO2020190754, publication date 2020-09-24) in view of Carlson et al. (US20030124028), Gardner et al. (Computers and Chemical Engineering 28 (2004) 943–953).
Efremov teaches as in the 35 USC 102 rejection supra and incorporated herein. In the alternative, Efremov 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 Efremov, 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 Efremov 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 Efremov 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 Efremov, 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 Efremov 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 Efremov 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.
Response to Remarks - 35 USC § 103
Applicant argues in the same manner as in the 35 USC 102 rejection. Applicant also argues that nothing in the cited references teach or suggest the claimed crystalline forms or conditions needed to produce the claimed polymorphs.
These arguments are is not persuasive because Efremov does teach the same compound in a solid form and as per MPEP 2112 (There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)), the crystalline form need not be recognized in the prior art to anticipate or render obvious. In addition, one of ordinary skill in the art would have combined the teachings of the prior art including the routine and automated steps of identifying polymorphs using the same conditions as in the instant application and arrive at the claimed invention with a reasonable expectation of success.
Double Patenting
Claims 1-2, 5-7, 45-54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5 and 7 of U.S. Patent No. US11590111. Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims the same compound (and share the same disclosure as Efremov) as in the instant claims and anticipates or renders obvious the instant claims as detailed in the 35 USC 102/103 rejections supra and incorporated herein.
Response to Remarks - Double Patenting
Applicant argues the ’111 patent is neither anticipated or rendered obvious for the same reasons as above. The argument is not persuasive for the same reasons provided above.
Applicant’s argument with respect to the ‘317 application is persuasive and that rejection is withdrawn.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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
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