Ex Parte Pathi et al

Patent Trial and Appeal BoardOct 31, 2012

11539932 (P.T.A.B. Oct. 31, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 11/539,932 10/10/2006 Srinivas Laxminarayan Pathi EEHC/25505US (4137-01200) 4571 30652 7590 10/31/2012 CONLEY ROSE, P.C. 5601 GRANITE PARKWAY, SUITE 750 PLANO, TX 75024 EXAMINER CHANG, CELIA C ART UNIT PAPER NUMBER 1625 MAIL DATE DELIVERY MODE 10/31/2012 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte SRINIVAS LAXMINARAYAN PATHI, SHASHI REKHA KANATHALA, MANISH GOPALDAS GANGRADE, RAJENDRA NARAYANRAO KANKAN, and DHARMARAJ RAMACHANDRA RAO __________ Appeal 2011-007168 Application 11/539,932 Technology Center 1600 __________ Before DEMETRA J. MILLS, LORA M. GREEN, and STEPHEN WALSH, Administrative Patent Judges. MILLS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134. The Examiner has rejected the claims for lack of written description and lack of enablement. We have jurisdiction under 35 U.S.C. § 6(b). Appeal 2011-007168 Application 11/539,932 2 STATEMENT OF CASE The following claims are representative of the claims on appeal. 1. A crystalline form A of topotecan hydrochloride having an XRPD pattern with peaks at 6.08, 6.94, 8.10, 9.96,10.16, 11.68, 12.28, 13.08, 13.62, 14.32, 15.44, 16.46, 16.56, 17.58, 18.42, 19.32; 20.14, 21.22, 21.88, 22.54, 22.72, 23.38, 24.14, 24.36, 24.78, 25.02, 25.50, 26.42, 26.86, 27.18, 27.44, 28.10, 28.76, 29.42, 29.68 and 30.02 °2θ (±0.2°). 6. A crystalline form A of topotecan hydrochloride having an FT-IR spectrum as shown in Figure 2. 7. A crystalline form A of topotecan hydrochloride having a water content in the range of about 10 to 12 wt%. 8. A crystalline form A of topotecan hydrochloride according to claim 1 comprising (4S)-topotecan hydrochloride. Cited References Dell’orco et al. US 2007/0117832 A1 May 24, 2007 Joel Bernstein, Polymorphism in Molecular Crystals, Clarendon Press Oxford 271-272 (2002). Zhang et al., Racemic Species of Sodium Ibuprofen: Characterization and Polymorphic Relationships, 92 J. PHARM. SCI. 1356-1366 (2003). Flack, Chiral and achiral crystal structure, 86 HELVETICA CHIMICA ACTA 905-921 (2003). Seddon, Pseudopolymorph: A Polemic, 6 CRYSTAL GROWTH & DESIGN 1087 (2004). Yokota et al., Chiral Separation by Crystal Size Difference, 37 J. CHEM. ENG. JAPAN 1284-1285 (2004). Appeal 2011-007168 Application 11/539,932 3 Dell’orco et al., Preparation of novel crystalline form of topotecan monhydrochloride pentahydrafte for treatment of viral and cancer related diseases, CA 142:487518 (2005). Dario Braga and Fabrizia Grepioni, Making crystals from crystals: a green route to crystal engineering and polymorphism, CHEM. COMMUN. 3635-3645 (2005). Fasel et al., Amplification of chirality in two-dimensional enantiomorphous lattices, 439 NATURE 439-452 (2006). Vogt et al., A study of variable hydration states in topotecan hydrochloride, 40 J. PHARM. BIOMED. ANALYSIS 1080-1088 (2006). Grounds of Rejection Claims 1-14, 16-18, and 20-21 are rejected under 35 U.S.C. § 112, first paragraph, as failing to comply with the written description requirement. Claims 1-21 are rejected under 35 U.S.C. § 112, first paragraph, as failing to comply with the enablement requirement. FINDINGS OF FACT The Examiner’s findings of fact are set forth in the Answer at pages 5- 8. Discussion Claims 1-14, 16-18, and 20-21 are rejected under 35 U.S.C. § 112, first paragraph, as failing to comply with the written description requirement. Appeal 2011-007168 Application 11/539,932 4 ISSUE The Examiner concludes that Nowhere was form A defined to be [sic] must contain 10- 12% water. It is unclear what does the term "topotecan hydrochloride form A" means. Does it always contains [sic] 10-12% water or it may contain water. What was the nature of the water, crystalline? channel? adsorbed? absorped? Is it the hydroscopic version of the crystal or it is a chemical identity and water is part of it. Please note that it is evidenced that topotecan hydrochloride may contain crystalline lattice bound water as well as coordinatively bound labile channel water (see US 2007/0117832 see p.3, [0035]). Further, no description was found whether the XPRD or the IR was taken for the topotecan hydrochloride crystal with or without water. (Ans. 6.) The Examiner argues that, “There is no description as to whether the figure 1 or 2 is corresponding to the S-crystal or a heterocrystal which contains the 4S-isomer.” (Ans. 7.) The Examiner argues that one “having ordinary skill in the solid chemistry art would expect that in this century, there is no good reason why the chemical identity of a product cannot be explicitly described.” (Id. at 5.) Appellants submit the Examiner has failed to establish a prima facie case that the pending claims do not comply with the written description requirement. (App. Br. 6.) Appellants argue that the Examiner incorrectly contends that in the Specification no definition of topotecan hydrochloride Form A was given and that support for amended claim 21 can be found on page 6, ¶ [0042], lines 1-4 of the instant application. (Id.) Appellants argue that “the shorthand ‘Form A’ was used to designate the novel polymorphic form of topotecan hydrochloride which was subsequently further characterized by XRPD peaks and FT-IR spectral data.” (Id. at 8.) Appeal 2011-007168 Application 11/539,932 5 As to the water content in claim 7, Appellants argue that, the Specification “explicitly recites that ‘[t]he topotecan hydrochloride form A of this invention has a water content in the range of 10 to 12%.’ See Application at 6, ¶ [0035], lines 1-2.” “Appellants contend that there is no requirement that the nature of the water in topotecan hydrochloride form A be defined.” (App. Br. 9.) The issue is: Does the written description support the invention as claimed? PRINCIPLES OF LAW “In the context of the written description requirement, an adequate prima facie case must . . . sufficiently explain to the applicant what, in the examiner’s view, is missing from the written description.” See Hyatt v. Dudas, 492 F.3d 1365, 1370 (Fed. Cir. 2007). As stated in Ariad Pharms., Inc. v. Eli Lilly and Co., [t]he test for sufficiency is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.… The term “possession,” however, has never been very enlightening. It implies that as long as one can produce records documenting a written description of a claimed invention, one can show possession. But the hallmark of written description is disclosure. Thus, “possession as shown in the disclosure” is a more complete formulation. Yet whatever the specific articulation, the test requires an objective inquiry into the four corners of the specification from the perspective of a person of ordinary skill in the art. Based on that inquiry, the specification must describe an invention understandable to that skilled artisan and show that the inventor actually invented the invention claimed. Appeal 2011-007168 Application 11/539,932 6 598 F. 3d 1336, 1351 (Fed. Cir. 2010) (en banc). ANALYSIS We conclude that the Examiner has not set forth a prima facie case of lack of written description of the pending claims. Appellants argue that “the shorthand ‘Form A’ was used to designate the novel polymorphic form of topotecan hydrochloride which was subsequently further characterized by XRPD1 peaks and FT-IR2 spectral data.” (App. Br. 8.) While the Examiner would prefer that the specific chemical identity or structure of the claimed compound be set forth in the Specification (Ans. 5), the Examiner has failed to provide evidence that one of ordinary skill in the art would not have been able to identify the crystalline form claimed from its XRPD peaks and FT-IR spectral data as claimed and set forth in the Specification. As to the water content in claims 3, 4 and 7, Appellants argue that the Specification “explicitly recites that “[t]he topotecan hydrochloride form A of this invention has a water content in the range of 10 to 12%.’ See Application at 6, ¶ [0035], lines 1-2.” (Id. at 9.) The Examiner has failed to rebut Appellants’ argument or show that the topotecan hydrochloride form A (i.e., as defined by its XRPD peaks and FT-IR spectral data) and as made by the Examples set forth in the 1 XRPD is an abbreviation for X-ray powder diffraction crystallography. 2 FT-IR is an abbreviation for Fourier transform infrared spectroscopy. Appeal 2011-007168 Application 11/539,932 7 Specification, does not have a water content in the range of 10 to 12% or does not produce the 4(S) isomer of topotecan. Thus, the Examiner has failed to show what is missing from Appellants’ Specification or why one of ordinary skill in the art would not have understood, from reading Appellants’ Specification, that Appellants were in possession of the claimed crystalline form A of topotecan, its 10- 12% hydrate, or 4(S) isomer. The written description rejection is reversed. Discussion Claims 1-21 are rejected under 35 U.S.C. § 112, first paragraph, as failing to comply with the enablement requirement. ISSUE The Examiner contends that the “claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.” (Ans. 7.) The Examiner further argues that Absent of [sic, an] explicit process of making an explicit water containing product or a chiral specific product, one having ordinary skill in the art would not expect such product with the nonhydrated solvents (see Braga et al. p.3640 right column) or with nonchiral material (see Fasel et al. and Yokota et al.) … Three examples were provided in the specification which did not employ water as reaction media and the relationship of the water content and how it was incorporated were not exemplified or explicitly enabled. No chiral material was employed in the examples and no description as to how either Appeal 2011-007168 Application 11/539,932 8 the S-crystal or the S-material in a heterochiral crystal was formed from the starting non-chiral material. (Id. at 7-8.) In sum, the Examiner argues the Specification does not disclose how to make the claimed 10-12% hydrate of topotecan. Appellants contend that the Examiner has failed to establish a prima facie case of lack of enablement. (App. Br. 11.) The Appellants argue that The Examiner's assertion that the claimed subject matter is inoperable is a mere conclusory statement that is unsupported and contravenes the experimental showings of the instant specification. Appellants disclose and claim a crystalline form A of topotecan hydrochloride. Appellants describe sufficient relevant identifying characteristics of this crystalline form (e.g., XRPD and FT-IR peaks) and methods for preparation of this form. . . . Appellants disclosed examples which employ methanol as a solvent. Nowhere in the specification is it disclosed that anhydrous methanol was used. The ordinarily skilled artisan would be aware that methanol typically contains from about 500 ppm to about 2000 ppm water.[3] Further, one of the Appellants' examples discloses the use of aqueous hydrochloride as a reagent which again can serve as a source of water for the formation of a hydrated product. Appellants are uncertain as to why the Examiner is unable to identify the various water sources present in the examples of the instant specification. (App. Br. 12-13.) Appellants argue that the ordinarily skilled artisan when given the benefits of this disclosure would be aware of basic chemistry and that the use of the (4S) isomer of topotecan hydrochloride of any crystalline 3 See evidence set forth in note 3 on page 12 of the Appeal Brief. Appeal 2011-007168 Application 11/539,932 9 form in the disclosed methodologies would result in the conversion of at least a portion of the (4S) isomer of topotecan hydrochloride to the instantly claimed Form A. (Id. at 13.) The issue is: Does the Specification enable how to make the claimed topotecan 10-12% hydrate and 4(S) isomer of topotecan? PRINCIPLES OF LAW The examiner bears the initial burden of showing nonenablement. See In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993). “[E]nablement requires that the specification teach those in the art to make and use the invention without ‘undue experimentation.’ . . . That some experimentation may be required is not fatal; the issue is whether the amount of experimentation required is ‘undue.’” In re Vaeck, 947 F.2d 488, 495 (Fed. Cir. 1991) (emphasis in original). Some experimentation, even a considerable amount, is not “undue” if, e.g., it is merely routine, or if the specification provides a reasonable amount of guidance as to the direction in which the experimentation should proceed. See In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). A claim may encompass inoperative embodiments and still meet the enablement requirement of 35 U.S.C. § 112, first paragraph. See Atlas Powder Co. v. E.I. du Pont De Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984), In re Angstadt, 537 F.2d 498, 504 (CCPA 1976). As noted in Amgen, Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1334 (Fed. Cir. 2003): Appeal 2011-007168 Application 11/539,932 10 The enablement requirement is often more indulgent than the written description requirement. The specification need not explicitly teach those in the art to make and use the invention; the requirement is satisfied if, given what they already know, the specification teaches those in the art enough that they can make and use the invention without “undue experimentation.” Also, significant experimentation does not preclude enablement: Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. . . . The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed. In re Wands, 858 F.2d 731, 736-37 (Fed. Cir. 1988) (citations omitted). ANALYSIS We conclude that the Examiner has not met the initial burden of showing nonenablement of the pending claims. The Examiner specifically argues that the Specification provides an insufficient description as to how to make the "water content" product or the 4S-isomer crystals. (Ans. 7.) “Absent of [sic] explicit process of making an explicit water containing product or a chiral specific product, one having ordinary skill in the art would not expect such product with the nonhydrated solvents (see Braga et al. p.3640 right column) or with nonchiral material (see Fasel et al. and Yokota et al.)” (Ans. 7.) The Examiner attempts to bolster his position with evidence such as Braga, arguing that Appellants Appeal 2011-007168 Application 11/539,932 11 failed to show that they possessed the hydrate form of topotecan since the state of the crystal hydrate art is unpredictable. (Id. at 9-10.) With respect to the 4S topotecan hydrochloride claims, the Examiner argues that, “[c]hiral crystal identification can be made only when the chrial [sic] ‘crystalline’ product was obtained and identified to be separable or inseparable. In [the] absence of chiral crystal separation/identification, one cannot obtain a chiral product in either homochiral product or hetero chrial [sic] product.” (Id. at 12.) We are not persuaded by the Examiner’s argument or evidence. Ultimately, the Examiner has failed to show that if one of ordinary skill in the art practices the Examples set forth in the Specification, one of ordinary skill in the art would not have obtained a topotecan crystalline form A having a water content in the range of about 10-12% and which comprises 4S topotecan isomer. Appellants argue that the Examples in the Specification result in a topotecan crystalline Form A. The Specification indicates at paragraph [0035] that topotecan hydrochloride Form A has a water content in the range of 10 to 12%. The Specification paragraph [0037] indicates that topotecan hydrochloride form A is provided in the form of the (4S)-isomer. Therefore there is a reasonable basis supporting that if one of ordinary skill in the art follows the Examples set forth in the Specification to obtain Form A the resulting product would be topotecan crystal Form A having a water content of 10-12% and comprising the (4S)-isomer. In In re Brana, 51 F.3d 1560, 1566 (Fed. Cir. 1995), the Federal Circuit stated that Appeal 2011-007168 Application 11/539,932 12 a specification disclosure which contains a teaching of the manner and process of making and using the invention ... must be taken as in compliance with the enabling requirement of the first paragraph of § 112 unless there is reason to doubt the objective truth of the statements contained therein which must be relied on for enabling support. Furthermore, [w]hen rejecting a claim under the enablement requirement of section 112, the PTO bears an initial burden of setting forth a reasonable explanation as to why it believes that the scope of protection provided by that claim is not adequately enabled by the description of the invention provided in the specification of the application; this includes, of course, providing sufficient reasons for doubting any assertions in the specification as to the scope of enablement. In re Wright, 999 F.2d at 1561-62. Thus, Appellants’ Specification must be taken as in compliance with the enablement requirement of the first paragraph of § 112, as the Examiner has not met the burden of providing sufficient reasons for doubting any assertions in the specification as to the scope of enablement or explaining why the Examples in the Specification do not result in a product with at water content of 10-12% or the 4S isomer of topotecan. CONCLUSION OF LAW The Examiner’s arguments do not support the Examiner’s lack of written description and lack of enablement rejections, which are reversed. REVERSED Appeal 2011-007168 Application 11/539,932 13 cdc