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/CN2021/102068 (06/24/2021)
and claims foreign priority to CHINA 202010610052.6 (06/29/2020).
Status
Claims 1-5, 11, 14, 16-18, 22-29 are pending. Claims 22-29 were newly presented.
Rejections not reiterated in this office action are withdrawn.
Amended 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 1-4, 11, 14, and new claims 22-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lou et al. (WO2020135771 (publication date 2020-07-02, EFD 2019-12-27), citations to English equivalent US20230068538).
Lou teaches compound 172 with the following structure ([1416]-[1417]):
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and preparation process that produced “the form of a white solid” ([1417]).
As per MPEP 2112:
“[T]he 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). Thus the claiming of a new use, new function or unknown property which is 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).
…
“[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on ‘inherency’ under 35 U.S.C. 102, on ‘prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same.” In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977) (footnote and citation omitted). The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (citing Best, 562 F.2d at 1255).
…
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). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp.v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985)
In this case, the prior art discloses the identical product, chemically, and as a “white solid” which is substantially identical to the product claimed. The scope of the claims are multiple “forms” including limitations to inherent properties of the product including XRPD, TGA, DSC, and NMR which were not disclosed by the prior art. In addition, the instant specification discloses that crystal forms spontaneously transform from one form to another, including among amorphous forms (p. 41-45). Thus, when weighed by a preponderance of the evidence, the record leads to the conclusion that a prima facie case of anticipation of claims 1-4 is established.
Similarly, the product-by-process claims 7-8 where the resulting product has the same structure as detailed above are also anticipated.
Regarding claims 11 and 14 to a pharmaceutical composition, Lou discloses the compound 172 administered in vivo as a pharmaceutical composition ([1625]).
Regarding new claims 22-24 to a crystalline form characterized by spectroscopy, as with claims 1-4 Lou discloses the same composition.
Response to remarks - 35 USC § 102
Applicant argues that Lou was obtained directly from the inventor of the current application and filed a 37 CFR 130 declaration of JUN LOU which was fully considered and which states:
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While such a declaration may be sufficient to overcome a rejection under 35 USC 102(a)(2), the claims are also rejected under 35 USC 102(a)(1) and the declaration does not avoid the rejection. Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Applicant argues that “Example 1, paragraphs [0186] and [0189] of the present specification, Applicant repeated the preparation process of compound 172 as described in Lou et al and confirmed that the resulting ‘white solid’ is the amorphous state of compound 172.”
The examiner has considered the argument and not found it persuasive. First, there is not “Example 1” in the instant specification and not at [0186] or [0189] in the specification as filed. The PGPUB US20230406850 has an “Embodiment 1” where an amorphous white solid is described, however assuming this Embodiment 1 is what Applicant is referring to, there are differences among that process and that disclosed by Lou such that it cannot be considered to be the same process. Furthermore, the instant claims are limited by spectroscopic characterization in a manner such that referring to a solid as amorphous does not meet Applicant’s burden in establishing that the prior art differs from the instant claims.
Amended 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 1-5, 11, 14, 16-18, and new claims 22-29 are rejected under 35 U.S.C. 103 as being unpatentable over Lou et al. (WO2020135771 (publication date 2020-07-02, EFD 2019-12-27), citations to English equivalent US20230068538) in view of Garceau et. Al (WO2020099923, publication date 2020-05-22), Carlson et al. (US20030124028), Gardner et al. (Computers and Chemical Engineering 28 (2004) 943–953).
Lou teaches as detailed in the rejection of claims 1-4, 11, 14, and 22-24 under 35 USC 102 supra and incorporated herein and further renders these claims obvious in view of the secondary references as detailed below. Lou also teaches work-up of the compounds includes recrystallization ([0402]) to produce “crystalline powders” ([0412]).
Regarding claims 5 and 25-26 to a preparation process specifying combining the compound in solvents, in ratios, at specified temperatures, and with mixing, Lou does not teach these steps. However, such crystallization steps would have been considered well-known and routine and are part of a required solid form optimization for pharmaceutical compounds as taught by the secondary references.
Garceau teaches crystalline forms of the P2X3 modulator “compound 1” for treating P2X3-associated disorders (abstract, [0053], claims 1-49) that is chemically similar to Lou’s compound 172:
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and shares the same utility. Garceau teaches the significant importance of identification and selection of the solid form in pharmaceutical compounds ([0057]: “a change in solid form may affect a variety of physical and chemical properties, which may provide benefits or drawbacks in processing, formulation, stability, bioavailability, storage, and handling (e.g, shipping), among other important pharmaceutical characteristics.”). Garceau teaches a screening process to discover the solid forms of compound by combining the compound with a variety of solvents using different ratios, mixtures, temperatures, and techniques ([0156]-[0165]).
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 Garceau, 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 Lou’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 Lou’s compound 172 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 (Specification [0196]-[0247]).
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 Lou, 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, Gardner, and Garceau (Carlson [0004]-[0005], [0010]-[0011]; Gardner Fig. 2, Fig. 5, p. 944-946, “3.1”, “3.2”, “3.3”; Garceau [0057]). 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 Lou 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 Lou’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”.
Regarding claims 16-18, and 27-29 to a method of treating a disease by administering the compound to a subject, Lou teaches the same scope (claims 22-23: “urinary incontinence” and “inflammatory pain”, [0430]).
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 that Lou is not prior art due to 35 USC 102(b)(2)(A). As with the response in the 35 USC 102 section supra, this argument is not persuasive.
Amended Double Patenting
Claims 1-5, 11, 14, 16-18, and new claims 22-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11, 19-22 of US Patent 12503468 (issuing from application 17417304) in view of over Lou et al. (WO2020135771 (publication date 2020-07-02, EFD 2019-12-27), citations to English equivalent US20230068538) in view of Garceau et. Al (WO2020099923, publication date 2020-05-22), Carlson et al. (US20030124028), Gardner et al. (Computers and Chemical Engineering 28 (2004) 943–953) as detailed in the 35 USC 103 rejection supra and incorporated herein. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims include compound 172 (i.e., claim 11, in the same family as Lou sharing the same disclosure). Furthermore, one of skill in the art construing the claims would have considered the same preparation process as disclosed in Example 172 which results in the same white solid. One of ordinary skill in the art would have also considered the same claimed method of use and arrive at the claimed invention.
Response to remarks – Double Patenting
Applicant argues that Lou is not prior art due to 35 USC 102(b)(2)(A). As with the response in the 35 USC 102 section supra, this argument is not persuasive.
Applicant also argues that “form III of claim 1 is fundamentally different from the pure compound itself”. This argument is not persuasive because, first, it is not clear what applicant is referring to by “fundamentally different”, and second, one of skill in the art construing the claims would have considered the disclosed preparation technique including Example 172 and in view of the secondary references had a reasonable expectation of success in arriving at the claimed invention.
Applicant also presented new data in Tables A, B, and C and argues how the data establishes nonobviousness. This is not persuasive because in order for the objective evidence to be of probative value in must be supported by actual proof and not simply attorney argument. See MPEP 716.01(c).
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.
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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