Ali Asaff Torres et al.

Patent Trials and Appeals Board

Feb 7, 2022

2020004572 (P.T.A.B. Feb. 7, 2022)

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. 12/253,943 10/18/2008 Ali Asaff Torres 2807-00500 1446 23505 7590 02/07/2022 CONLEY ROSE, P.C. 575 N. Dairy Ashford Road Suite 1102 HOUSTON, TX 77079 EXAMINER PYLA, PAUL D ART UNIT PAPER NUMBER 1653 NOTIFICATION DATE DELIVERY MODE 02/07/2022 ELECTRONIC 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. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): pathou@conleyrose.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte ALI ASAFF TORRES, MAYRA DE LA TORRE MARTINEZ, ANTONINO BERRONDO MIR, and ROBERTO MIGUEL MACIAS OCHOA __________ Appeal 2020-004572 Application 12/253,943 Technology Center 1600 __________ Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN, and ROBERT A. POLLOCK, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1 under 35 U.S.C. § 134 involving claims to a cyclic process to produce vanillin from ferulic acid or a salt thereof. The Examiner rejected the claims as failing to comply with the enablement requirement. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the Real Party in Interest as Laboratorios Minkab, S.A. DE C.V. (see Appeal Br. 3). We have considered the Specification filed Oct. 18, 2008 (“Spec.”); Final Action of Apr. 30, 2019 (“Final Act.”); Appeal Brief filed Sept. 30, 2019 (“Appeal Br.”); and Examiner’s Answer filed Feb. 26, 2020 (“Ans.”). Appeal 2020-004572 Application 12/253,943 2 Statement of the Case Background “Vanillin is a compound broadly used as a flavor for the food industry, as an aroma in the cosmetic industry and as a precursor for the chemical synthesis of drugs for the pharmaceutical industry” (Spec. 1). Previous processes “to obtain vanillin by alternative biological processes which use microorganisms . . . involve three steps: sterilization of the equipment, a fermentation period to allow for the growth of the microorganisms, and a biotransformation period, in order to convert ferulic acid into vanillin” (id.). “Unfortunately, all of these processes suffer from the disadvantage of having batches that require the above three steps” (id.). The Claims Claims 20-23, 26, 29, 30, 33-36, 38, and 39 are on appeal. Claim 20 is an independent claim, is representative and reads as follows: 20. A cyclic process to produce vanillin from ferulic acid or a salt thereof, comprising: (a) preparing a solid support system comprising one or more pieces of an inert, porous, absorbent and compressible material, having a bed height between 1 cm and 10 cm in a container and thereby being configured for aeration and promoting-mycelial growth on a surface area of between 3000 cm2 per gram of the solid support and 4000 cm2 per gram of the solid support; (b) impregnating the solid support system with a liquid culture broth inoculated with Streptomyces setonii strain ATCC39116; (c) Growing Streptomyces setonii strain ATCC39116 at a maximum specific growth rate of 0.71 h-1 on the surface culture promoted by the solid support system; (d) Draining the exhausted culture broth to produce a drained-immobilized surface culture from Streptomyces setonii Appeal 2020-004572 Application 12/253,943 3 strain ATCC39116; (e) Impregnating the drained-immobilized surface culture from Streptomyces setonii strain ATCC39116 with a solution of ferulic acid or a salt thereof; (f) incubating the solution and the immobilized surface culture comprising Streptomyces setonii strain ATCC39116; (g) producing vanillin from ferulic acid by the surface culture at a rate of 12.18 x10-4 moles h-1; (h) collecting the solution comprising vanillin by force from the solid support system; and (i) repeating steps (e)-(h), said steps (e)-(h) are repeated between 3 and 15 times, said surface culture yielding a percentage conversion of ferulic acid or a salt thereof to vanillin of at least 70%. The Rejection2 The Examiner rejected claims 20-23, 26, 29, 30, 33-36, 38, and 39 under 35 U.S.C. § 112(a) as failing to comply with the enablement requirement (Final Act. 3-5). The Examiner finds the claims do not enable one of ordinary skill in the art to use the invention to produce vanillin and achieve the goals of the claims (i.e., achieving a surface culture at a specific growth rate of 0.71 h-1 (as claimed), producing vanillin from ferulic acid by the surface culture at a rate of 12.18 x 10-4 moles h-1 (as claimed), and achieving a percentage conversion of ferulic acid to vanillin of at least 70% by repetition of the claim steps) since there are particular culture conditions that achieve the claimed rates missing from the claims which are critical in achieving such goals. (Final Act. 5). 2 We note that the Examiner withdrew the claim objection and withdrew the obviousness rejection over claim 40 (see Ans. 3). Appeal 2020-004572 Application 12/253,943 4 The issue with respect to this rejection is: Does a preponderance of the evidence of record support the Examiner’s conclusion that the claims fail to comply with the enablement requirement? Findings of Fact Breadth of Claims 1. Claim 20 is very narrowly drawn to particular solid support requirements, a particular microorganism, Streptomyces setonii strain ATCC39116, a particular maximum growth rate, a particular production rate, and a particular conversion percentage of at least 70%. Presence of Working Examples 2. The Specification has three specific working examples (see Spec. 8-11) Amount of Direction or Guidance Presented 3. The Specification teaches “the Streptomyces setonii ATCC 39116 strain” (Spec. 3). 4. The Specification teaches a “solid support structure, like polyurethane foam” and teaches the solid support structure “has the characteristics of being of one or more pieces of a material which is effectively inert, porous, and absorbent” (Spec. 3). The Specification teaches use of a support with a “foam density goes from 0.005gml-1 to 0.070gml-1; the desirable density being 0.015gml-1 to 0.025gml-1” (id.). 5. The Specification teaches two different culture broths, a first culture broth composed of “10gl-1 of glucose, 4gl-1 of yeast extract, 4gl-1 of Na2HPO4, 1gl-1 of KH2PO4, 0.2gl-1 of MgSO4 7H2O, 0.2gl-1 of NaCl and 0.05 gl-1 of CaCl2·H2O, with a pH of 7.2” and a second culture broth composed of “15gl-1 of glucose, 6gl-1 of yeast extract, 4gl-1 of Na2HPO4, 1gl-1 Appeal 2020-004572 Application 12/253,943 5 of KH2PO4, 0.2gl-1 of MgSO4 7H2O, 0.2gl-1 of NaCl and 0.05gl-1 of CaCl2 . H2O, with a pH of 7.2” (Spec. 8-9). 6. The Specification teaches, more generally, that: An adequate culture broth contains a carbon source, a nitrogen source, inorganic salts and growth factors. Different sugars, preferably, mono or disaccharides, preferably glucose and/or maltose in a concentration of approximately 8gl-1 to approximately 40gl-1, preferably of approximately 15gl-1 to approximately 30 gl-1 are used as a source of carbon. Yeast extract, which contains nitrogen growth factors and trace elements, is used in a concentration of approximately 1gl-1 to approximately 15gl-1, preferably in a concentration of approximately 3gl-1 to approximately 10gl-1. Additionally, a magnesium source and a phosphate buffer (of pH 7 to pH 8) are used. The culture broth is sterilized. (Spec. 4-5). 7. The Specification teaches the “biotransformation is carried out at a temperature ranging from 86°F to 113°F” (Spec. 3). 8. The Specification teaches the biotransformation phase begins at the moment of the feeding and has a duration of 7 to 48 hours, preferably from 15 to 28 hours; after this period almost all of the precursor has been consumed and transformed into vanillin and some minor byproducts. Once the biotransformation phase is finished, the foam containing the immobilized biomass is again squeezed and compressed in order to separate the biotransformation solution containing vanillin. The recovered solution carries a small quantity of cellular material that is separated by centrifugation or filtration in order to purify the vanillin. The immobilized microorganisms, in the foam that is free of the biotransformation solution, are again ready to begin a new biotransformation cycle by feeding them a fresh solution of ferulic acid. The system maintains its efficiency and conversion rate from 3 to 15 cycles, preferably 6 to 10 cycles, Appeal 2020-004572 Application 12/253,943 6 after which a loss of cellular viability takes place as well as a gradual reduction of the biomass. (Spec. 5). State of the Prior Art and Unpredictability of the Art 9. The Examiner asserts, without direct evidence, that If the features of the growth rate and vanillin production rate are not inherent properties of Streptomyces setonii strain ATCC39116 (which as noted above is the same microorganism known to produce vanillin from ferulic acid), there is no support within the four corners of the document that would provide sufficient guidance as to how to achieve the claimed specific growth, production and conversion rates based on the limitations within the claims since there are missing elements or steps that would be needed in order to achieve such the recited growth rate and vanillin production rates and achieve the goals of the claims as instantly written. (Ans. 10). 10. The Examiner finds “Appellant is also requiring specific vanillin production rates but does not provide the necessary steps or conditions within the claims how these rate are achieved” (Ans. 9). 11. The Examiner cites no evidence regarding either the state of the art or the unpredictability of the art. 12. Muheim,3 prior art cited by the Examiner in the withdrawn obviousness rejection, teaches the production of vanillin comprises cultivating first in a nutrient broth a microorganism of the genus Streptomyces . . . preferably the bacterium Streptomyces setonii, wherein, preferably, the cultivating period is about 5-40 hours and lasts, until the carbon source glucose is (almost) consumed, then 3 Muheim et al, EP 0885968 B1, published Feb. 22, 2006. Appeal 2020-004572 Application 12/253,943 7 adding the substrate ferulic acid in the range of about 5-40 gL-1 of fermentation broth, either continuously or batch-wise. (Muheim 10). 13. Krishna,4 prior art cited by the Examiner in the withdrawn obviousness rejection, teaches a number of studies have been performed for bioprocess intensification, and to elucidate the optimal conditions for the synthesis of various secondary metabolites. Bioprocess intensification focuses on optimizing fermentation yields via media composition and feed strategies, dynamic control of physical conditions, induction, genetics, immobilization and bioreactor engineering. (Krishna 23, col. 1). Quantity of Experimentation 14. The Examiner makes no finding with regard to the quantity of experimentation required, and cites no evidence suggesting a large amount of experimentation would have been required to achieve the production conditions recited in claim 20. 15. The Torres Declaration5 states: Each element required by independent claim 20 in order to achieve a maximum specific growth rate of bacteria (0.71 h-1), average conversion rate of ferulic acid to vanillin (12.18 x 10-4 moles h-1) and a molar conversion from ferulic acid to vanillin of at least 70% is clearly taught by the instant specification and particularly at Figures 3 and 4, and Examples 1 and 2. (Torres Declaration ¶ 9). 4 Krishna, Solid-State Fermentation Systems - An Overview, 25 Critical Reviews in Biotechnology 1-30 (2005). 5 Torres Declaration, dated Oct. 1, 2017. Appeal 2020-004572 Application 12/253,943 8 Skill in the Art 16. Dr. Ali Asaff Torres, a senior scientist for 9 years (see Torres Decl. ¶ 3), “observed the level of skill of a number of persons working in the areas of Food Science. In [Dr. Torres] opinion, the ordinary level of skill of a person working in those fields is that of a person having a post-graduate degree and 5 to 10 years experience in Food science and/or bioprocessing” (Torres Decl. ¶ 5). Principles of Law Factors to be considered in determining whether a disclosure would require undue experimentation . . . include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). Analysis “A threshold issue is whether the PTO met its burden of proof in calling into question the enablement of appellant’s disclosure. This burden required that the PTO advance acceptable reasoning inconsistent with enablement.” In re Strahilevitz, 668 F.2d 1229, 1232 (CCPA 1982). “Thereupon, the burden would shift to appellant to show that one of ordinary skill in the art could have practiced the claimed invention without undue experimentation.” Id. The Examiner has provided argument, not evidence or scientifically- based reasoning, challenging the enablement of claim 20. That is, the Examiner asserts that “there are particular culture conditions that achieve the Appeal 2020-004572 Application 12/253,943 9 claimed growth rate and vanillin production rates missing from the claims which are critical in achieving such goals” and that the claims are not enabled “unless Appellant can state on the record that the full range of actual growth conditions claimed will inherently yield these results” (Ans. 12). But the Examiner does not cite evidence or persuasive reasoning that there is any degree of unpredictability in optimizing culture conditions to yield the desired results. The Examiner does not cite evidence that there is a low level of skill or evidence that a large quantity of experimentation would be required. The Examiner does not point to prior art references that support a finding that undue experimentation would be required. In contrast, Appellant presents very narrow claims, limited to particular types of solid support systems, a very particular strain of microorganism, Streptomyces setonii strain ATCC39116, a particular starting material, ferulic acid, and particular yield and rate conditions (FF 1). The Specification provides three working examples (FF 2). The Specification provides guidance on solid supports (FF 4). The Specification provides both specific and more general descriptions of working culture broths (FF 5-6). The Specification provides guidance regarding temperature, pH, timing, and cycle conditions for the production process (FF 7-8). As to predictability, Muheim shows that a similar process for producing vanillin from ferulic acid that does not involve a solid support functions (FF 12). Krishna teaches that solid support production processes may be optimized for yield (FF 13). Dr. Torres states in unrebutted testimony that the skill level is quite high (FF 16). Appeal 2020-004572 Application 12/253,943 10 Therefore, we find that the Examiner has not provided evidence and reasoning sufficient to support the lack of enablement conclusion. Indeed, while the Examiner also appears to be challenging the scope of enablement of claim 20, there is insufficient evidence to support this finding as well. And to the extent that the burden would shift to Appellant, there is sufficient rebuttal evidence supporting enablement in the Specification, the working examples, the prior art, and the Torres Declaration (FF 1-8, 12-16). Conclusion of Law A preponderance of the evidence of record does not support the Examiner’s conclusion that the claims fail to comply with the enablement requirement. DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 20-23, 26, 29, 30, 33- 36, 38, 39 112(a) Enablement 20-23, 26, 29, 30, 33- 36, 38, 39 REVERSED