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 has PRO 63/431,330 (12/09/2022).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-11, 13-16 are rejected under 35 U.S.C. 102(a)(1) and (2) as being anticipated by Brenneman et al. (WO2014039434).
Brenneman has claim 10 to compound 114:
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which is identical to Compound 1 of instant claim 1. Brenneman teaches that the claims include “pharmaceutically acceptable salts thereof and solvates thereof such as for instance hydrates including solvates of the free compounds or solvates of a salt of the compound” (p. 46). Brenneman has claim 13 to pharmaceutical compositions comprising the compound. Brenneman has claim 17 to treating diabetic nephropathy (a diabetic kidney disease) by administering the compound to a patient.
Regarding the “solid crystalline form” and “characterized by” language of the instant claims, although Brenneman teaches the claims include solid forms and the preparation of the compound the reference does not disclose the spectroscopic data (XRPD, 13C solid-state NMR) of the instant claims. 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, Brenneman 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 13C 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, 13C solid-state NMR chemical shift 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.”)
The instant specification characterizes the Brenneman compound as amorphous, however, the specification does not describe in detail (including technical details of preparation and spectroscopy) how the determination was made such that the assertion does not make clear whether all of Brenneman’s disclosure of solid forms must be amorphous. 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 6-9 to a pharmaceutical composition, Brenneman teaches the same pharmaceutical composition (claim 13). Regarding claims 10-11 to a method of treating disease, Brenneman teaches the same method (claim 17 to treating diabetic nephropathy (a diabetic kidney disease) by administering the compound to a patient). Regarding claims 13-16, specifically to Form I, as with claims 1-11, the prior art teaches the same invention.
Thus, the claims are anticipated.
Response to Remarks - 35 USC § 102
Applicant argues:
Example 7 of Brenneman describes the preparation of its compound 1 including the final steps of "purif[ication] by gradient elution (10- 100% MeCN/water + 0.1 % HCO2H) on a Gilson RP-HPLC. Concentrated in vacuo to afford title compound 1 (64.0 mg)." (See Brenneman at page 68, first full paragraph.) There is no further description, teaching or even a suggestion that a solid form of 1 was prepared.
This argument is not persuasive because one of skill in the art would have recognized that the product produced was a solid and, in addition, the instant specification on page 4 states:
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which evidences that the prior art does in fact teach the solid form. Furthermore, in the instant application is Fig. 5 which has the following X-ray powder diffraction pattern of the Brenneman product:
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which shows 2-theta peaks at the positions indicated in the claims as annotated by Examiner above. Although the Fig. 5 peaks are at low intensity, they are present, and as evidenced by Tiwari et al. (Journal of Pharmaceutical and Biomedical Analysis 43 (2007) 865–872) and Hurst et al. (Analytica Chimica Acta 337 (1997) 233-252: “Terms like ‘amorphous, well- and poorly-crystallized’ are often misleading as applied to diffraction patterns. Broad, low, poorly resolved peaks and missing reflections, sometimes regarded as indicative of poor crystallinity, can be due as well to smallness and misorientation of coherent diffraction domains (CDDs).”; Table 1) would be the result of experimental factors not disclosed by Applicant - see, for example, Tiwari Fig. 3, Hurst Table 1. Therefore, the record establishes 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”. Rejection maintained.
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.
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.
In the alternative, claims 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Brenneman et al. (WO2014039434) in view of Carlson et al. (US20030124028), Gardner et al. (Computers and Chemical Engineering 28 (2004) 943–953).
Brenneman teaches as in the 35 USC 102 rejection supra and incorporated herein. In the alternative, Brenneman 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), heating/cooling, acids ([0014]-[0019]; [0257]), seeding ([0131], [0141]), and isolating (claim 26-27).
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 Brenneman, 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 Brenneman 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 Brenneman 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 Brenneman, 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 Brenneman 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 Brenneman 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 “Nothing in in the combination of references provides any suggestion that a solid crystalline form of Brenneman's compound 114 could be prepared, let alone a compound having the characteristics recited in the claims”.
This argument is not persuasive as addressed in the response to the 102 remarks above.
Applicant argues nothing in Brenneman in view of Carlson and Gardner teaches how the combination of solvents, temperature, concentration, etc. would affect the crystallization of compound 114 as set forth in Grunenthal.
Applicant’s argument is not persuasive because Carlson and Gardner specifically teach how to screen the crystallization conditions of a given pharmaceutical and one of skill in the art would have found to be reasonably applicable to Brenneman’s compound 114. Regarding the case of nonobviousness in Grunenthal GMBH v.Alkem Labs. Ltd., 919 F.3d 1333, 1343 (Fed. Cir. 2019), the argument is not persuasive because there are substantial evidentiary differences distinguishing the present case from Grunenthal, including that the burden of proof is “preponderance of the evidence,” see MPEP 706 I,1 whereas in Grunenthal the burden of proof was the higher burden of “clear error”. In addition, the Federal Circuit explained that “on the record here, the district court did not clearly err”:
Our decision today does not rule out the possibility that polymorph patents could be found obvious. But on the record here, the district court did not clearly err in finding a failure to prove that a POSA would have had a reasonable expectation of success at arriving at the claimed invention based on the prior art.
Grunenthal at 1344-45 (Fed. Cir. 2019). Unlike Grunenthal where the court found the evidence of record lacked a “detailed enabling methodology”2 for polymorph screening, here Carlson and Gardner provide evidence of available automated systems and examples of successfully screening pharmaceuticals for polymorphic forms that one of ordinary skill in the art could readily utilize.
A further distinction among the present case and Grunenthal is that the court found there was a lack of an expectation of success because the evidence of knowledge in the field was such that a POSA would not know whether the compound was polymorphic or how to conduct a screen for polymorphism. Id. at 1434. In contrast, Carlson and Gardner establish factually that those of ordinary skill in the art would be expected to screen for solid forms of a pharmaceutical in the course of routine optimization. Thus, one of ordinary skill in the art would have had a reasonable expectation of success using the known screening techniques to determine whether a polymorphic crystalline form exists. In other words, one of ordinary skill in the art would have always considered screening for solid forms using the known techniques in the routine course of pharmaceutical development.
Double Patenting
Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-14, 19 of U.S. Patent No. US-RE46886 in view of Brenneman et al. (WO2014039434), 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 (in the same family as Brenneman sharing a disclosure) claims the same compound as in the instant claims and as detailed in the above rejections renders the claims anticipated or obvious.
Response to Remarks - Double Patenting
Applicant argues tin the same manner as in the 35 USC 103 rejection. This argument is not persuasive for the same reasons. Rejection maintained.
Conclusion
No claims allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at (571) 270-5293. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
1 MPEP 706 I:
The standard to be applied in all cases is the “preponderance of the evidence” test. In other words, an examiner should reject a claim if, in view of the prior art and evidence of record, it is more likely than not that the claim is unpatentable.
2 Grunenthal GMBH v. Alkem Labs. Ltd., 919 F.3d 1333, 1345 (Fed. Cir. 2019) (“Rather, Byrn simply provides "a general approach" to polymorph screening, only giving "general guidance," without providing "detailed enabling methodology."”)
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