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 .
DETAILED ACTION
1. Applicant’s election of Group I (claims 1-13 & 15-20) without traverse in the reply filed on 10/23/25 is acknowledged.
2. Claims withdrawn:
Claim 14 is withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
3. Priority
Applicant’s claim for domestic priority under 35 U.S.C. 119(e), filed 10/30/20, is acknowledged.
4. IDS
IDS filed 4/28/23 is acknowledged. A signed copy of the IDS is provided with this Office Action.
5. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
6. 35 U.S.C. § 112, first paragraph (Written Description)
Claims 1-13 & 15-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claimed invention is directed to:
1. (Currently Amended) Fermentative A process for fermentative production of isoprenoids with less than 40 carbons as backbone in a two-phase culture system, comprising in situ extraction of said isoprenoids, wherein the process comprises cultivating a suitable host cell is cultivated in the presence of a carbon source and a lipophilic solvent, and with a minimal loss of the lipophilic solvent during the fermentation process, wherein the lipophilic solvent is different from the carbon source.
2. (Currently Amended) The process according to claim 1, wherein the lipophilic solvent present at the end of the fermentation is at least 80% of the lipophilic solvent present at the start of the fermentation process.
3. (Previously Presented) The process according to claim 1, wherein the lipophilic solvent comprises isoparaffins.
4. (Currently Amended) The process according to claim 1, wherein the lipophilic solvent comprises alkanes.
5. (Currently Amended) The process according to claim 1, wherein the fermentation product is selected from the group consisting of apocarotenoids [[,]] and sesquiterpenes.
6. (Currently Amended) The process according to claim 1, wherein the carbon source is selected from linear alkanes, free fatty acids, ethanol, glucose and triglycerides.
7. (Currently Amended) The process according to claim 1, wherein 20% or less of the lipophilic solvent is lost during the fermentation.
8. (Currently Amended) The process according to claim 1, wherein the consumption of the lipophilic solvent by the host cell is reduced by at least about 50%.
9. (Currently Amended) The process according to claim 7, wherein the evaporation of the lipophilic solvent is reduced by at least about 50%.
10. (Currently Amended) The process according to claim 1, wherein the formation of by- products or impurities is reduced by at least about 25%, wherein the impurities are selected from retinal, retinol, fatty acid retinyl esters (FAREs), dihydro-retinol, dihydro-retinyl acetate, dihydro FAREs, rosafluene, phytoene, ergosterol, and dihydro-beta-ionone.
11. (Currently Amended) The process according to claim 1, wherein the host cell is a fungal cell.
12. (Currently Amended) The process according to claim 1 for production of retinyl acetate, further comprising collecting the fermentation product in said lipophilic solvent.
13. (Currently Amended) The process according to claim 20, wherein the translucent color corresponds to PMS 120-129 according to the Pantone® Matching System (PMS).
15. (New) The process according to claim 4, wherein the lipophilic solvent comprises iso- alkane or cycloalkanes.
16. (New) The process according to claim 5, wherein the fermentation product is selected from the group consisting of retinoids and ionones.
17. (New) The process according to claim 5, wherein the fermentation product is selected from the group consisting of retinyl acetate, alpha-ionone, and beta-ionone.
18. (New) The process according to claim 6, wherein the carbon source comprises oleic acid, palmitic acid, linoleic acid, or oil originated from corn, soy, olive, sunflower, canola, cottonseed, rapeseed, sesame, safflower, grapeseed or mixtures thereof.
19. (New) The process according to claim 11, wherein the host cell is selected from Yarrowia, Rhodosporidium, Lipomyces, Saccharomyces and Rhodotorula.
20. (New) The process according to claim 12 further comprising isolating the fermentation product and measuring the color of the fermentation product, wherein the color is translucent or light yellow.
The claims are described by limitations without providing or describing the process steps necessary for a workable method. The claimed invention encompasses a genus of methods not adequately described.
For example, Claim 1 and claim 2, are described as a result-to-be-achieved which merely amounts to a statement of the underlying problem, without providing the technical features necessary for achieving this result. The skilled person trying to solve the problem posed by claims 1-2 would need to test a vast amount of lipophilic solvents under different culture/fermentation conditions using many different suitable host cells which cultivated in the presence of said solvent would produce isoprenoids with less than 40 carbons as backbone and, wherein the solvent would be present at the end of the fermentation process with minimal loss.
The instant specification describes a process for fermentative production of isoprenoids with less than 40 carbons as backbone in a two-phase culture system, comprising in situ extraction of said isoprenoids, wherein the process comprises cultivating a fungal host cell is cultivated in the presence of a carbon source and a lipophilic solvent, and with a minimal loss of the lipophilic solvent during the fermentation process, wherein the lipophilic solvent comprises isoparaffins or alkanes and the fermentation product is selected from the group consisting of apocarotenoids and sesquiterpenes and wherein the carbon source is selected from linear alkanes, free fatty acids, ethanol, glucose and triglycerides.
The instant specification does not describe the species claims as claimed.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe aninvention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what isclaimed."). Thus, an applicant complies with the written description requirement "bydescribing the invention, with all its claimed limitations, not that which makes it obvious,"and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966."Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents" of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents" of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case is discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
Moreover, Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir.1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
7. Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1 & 2 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over WO2019/058,000A1 and Jang et al. (2014) Biotech. Letters 36: 497-505.
Background In summary, while retinoids are a subset of isoprenoids, they are not the same as all isoprenoids. Chemically, retinol is an isoprenoid; isoprenoids are a group of compounds that includes vitamins E and K and cholesterol, which are synthesized from isoprene units. As shown in Figure 1, retinol is a hydrocarbon molecule with a single hydroxyl group at one end. This hydroxyl group can be oxidized to form an aldehyde group (yielding retinal), or to a carboxylic acid group (yielding retinoic acid). Retinal and retinoic acid are the biologically active forms of retinol. In addition to these different oxidation states, retinol occurs as a number of different isomers . The retinol structure shown in Figure 1 is all- trans -retinol, as all of the double bonds are in the trans configuration. Many cis isomers also occur. Two important examples are 11- cis -retinal, which is required for vision (see Figure1), and 13- cis -retinoic acid (or isotretinoin), which is used as an anti-acne drug. Retinol is a specific type of retinoid.
WO2019/058,000A1 teaches (page 1, lines 2-6; page 2, lines 1-6; examples 1-5; claims 1,2) a carotenoid-producing host cell, particularly fungal host cell, comprising: (a) stereoselective beta-carotene oxidizing enzyme (BCO), said host cell producing a retinal mix comprising cis- and trans-retinal, wherein the percentage of trans-retinal in the mix is at least about 65-98% or up to 100% produced by said host cell; and (b) an acetyl transferase (ATF) [EC 2.3.1.84] enzyme that catalyzes the conversion of retinol to a retinyl acetate mix, wherein the mix comprises at least about 65-98% or up to 100% retinyl acetate, at least 65-90% retinyl acetate, in trans- isoform.
Surprisingly, we now could identify a process for production of retinyl esters, particularly retinyl acetate, using a modified host organism, such as a carotenoid-producing host cell, particularly fungal host cell, comprising and expressing genes involved in the conversion of beta-carotene to retinyl acetate, 5 with a total conversion of at least about 10% towards generation of retinal and with a percentage of trans-retinyl acetate of at least 65%. The reference does not teach two-phase culture system of microorganisms producing isoprenoids
In situ extraction process from a two-phase culture system of microorganisms producing isoprenoids such as e.g. retinoids are known from Jang et al. (2014).
AS indicated in the written description requirement in paragraph 6, Claim 1 and claim 2, are described as a result-to-be-achieved which merely amounts to a statement of the underlying problem, without providing the technical features necessary for achieving this result. The skilled person trying to solve the problem posed by claims 1-2 would need to test a vast amount of lipophilic solvents under different culture/fermentation conditions using many different suitable host cells which cultivated in the presence of said solvent would produce isoprenoids with less than 40 carbons as backbone and, wherein the solvent would be present at the end of the fermentation process with minimal loss.
Based on the above facts It would have been obvious before the effective filing date of the claimed invention for one of ordinary skill in the art of enzymology/biochemistry to combine the teachings of WO2019/058,000A1 and Jang et al. (2014) Biotech. Letters 36: 497-505 in order to develop the process of claims 1 & 2 and do so with a reasonable expectation of success. One of ordinary skill in the art would have been motivated in view of the importance of retinoid production industrially, shorten the production process or cost and its use in cosmetic industry for one as shown in the concluding paragraph of Jang et al. Thus, the claimed invention was within the ordinary skill in the art to make and use at the time was made and was as a whole, prima facie obvious.
8. No claim is allowed.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. 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, Robert B Mondesi can be reached on 408 918 7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940