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 .
Detail Action
Claims 1- 20 submitted on 7/12/23 are pending for examination.
Applicants without traverse elected Claims 1-6, 10-20; directed to method for producing an objective substance, the method comprising: cultivating yeast having an ability to produce the objective substance in a culture medium containing a fatty acid, wherein the objective substance is selected from the group consisting of phytosphingosine (PHS) and phytoceramide (PHC) and species selection of NEM1 from claim 4, myristic acid from claim 2 and cyclodextrin from claims 12-13. Claims 7-9 are withdrawn belonging to claims comprising non-elected species.
Claims 1-6, 10-20 are for examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/12/2023, 5/5/2026 in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the IDS statement.
Claim Rejections
Claim Rejections, 35 U.S.C 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-6, 10-20 are rejected under 35 U.S.C. 112, first paragraph, as containing 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(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed to method of producing an objective comprising cultivating yeast having an ability to produce the objective substance in a culture medium containing a fatty acid, wherein the objective substance is selected from the group consisting of phytosphingosine (PHS) and phytoceramide (PHC) wherein expression and/or activity of a protein encoded by a gene selected from the group consisting of LAG1, LAC1, LIP1, NEM1, SPO7, LCB4, LCB5, ELO3, CKA2, ORM2, CHA1, and combinations thereof is reduced as compared with a non-modified yeast, or wherein the objective substance is PHC, and the yeast has been modified so that expression and/or activity of a protein encoded by a gene selected from the group consisting of YPC1, NEM1, SPO7, LCB4, LCB5, ORM2, CHA1 ( claims 4-7).
It is noted that MPEP 2111.01 states that "[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow." In this case, in light of the specification, the examiner has broadly interpreted the claims by reciting “ any yeast ( claims 1-3, 10-20 or modified yeast having its some genes having any structure modified or expressed ( claims 4-6) or , gene reduced from any source comprising any structure that capable of producing any phytosphingosine (PHS) and phytoceramide (PHC).
Therefore in light of the above interpretation the claims are broadly interpreted any yeast or modified yeast having its few genes reduced wherein said genes having any structure reduced or modified by any means.
The Court of Appeals for the Federal Circuit has recently held that 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." University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical).University of Rochester v. G.D. Searle & Co. (69 USPQ2d 1886 (2004)) specifically points to the applicability of both Lilly and Enzo Biochemical to methods of using products, wherein said products lack adequate written description. While in University of Rochester v. G.D. Searle & Co. the methods were held to lack written description because not a single example of the product used in the claimed methods was described, the same analysis applies wherein the product, used in the claimed methods, must have adequate written description (see Enzo paraphrased above).
In this case, there is no structure associated with function with regard to the members of the genus of yeast or modified yeast having its genes LAG1, LAC1, LIP1, NEM1, SPO7, LCB4 of any structure reduced by any means so that said yeast having specific activity of producing any phytosphingosine (PHS) and phytoceramide (PHC).. The specification discloses the Saccharomyces cerevisiae strains BY4742 (ATCC 201389; EUROSCARF Y10000), S288C (ATCC 26108) and modified yeast strain which CKA2 gene of nucleotide sequence of SEQ ID NO: 29 is deleted and overexpressed LCB1.
The genus of yeast strain or modified yeast strain having any polypeptides and encoding polynucleotides having specified activity modified in the claimed invention is an extremely large structurally and functionally variable genus. An argument can be made that the recited genus of polypeptides is adequately described by the disclosure of the structure of Saccharomyces cerevisiae strains BY4742 (ATCC 201389; EUROSCARF Y10000), S288C (ATCC 26108) and modified yeast strain BY4742 which CKA2 gene of nucleotide sequence of SEQ ID NO:29. However, the art clearly teaches there is a practical limits to predict function of a polypeptide based structural homology:
A. Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that "Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, and page 105).
B. Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340,) also highlight the difficulties associated with "Prediction of protein function from protein sequence and structure": "To reason from sequence and structure to function is to step onto much shakier ground", closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein's role fundamentally (page 323, paragraph 1).
C. This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polypeptides do not necessarily share the same function and many functionally similar proteins will have little or no structural homology to disclosed proteins. For example, proteins having similar structure have different activities (structure does not always correlate to function); Witkowski et al., (Biochemistry 38:11643-11650, 1999) teaches that one conservative amino acid substitution transforms a beta -ketoacyl synthase into a malonyl decarboxylase and completely eliminates beta-ketoacyl synthase activity. The art also teaches that functionally similar molecules have different structures; Kisselev L., (Structure, 2002, Vol. 10: 8-9) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
As stated above, no information beyond the characterization of a few species; Saccharomyces cerevisiae strains BY4742 (ATCC 201389; EUROSCARF Y10000), S288C (ATCC 26108) and modified yeast strain which CKA2 gene of nucleotide sequence of SEQ ID NO: 29 having specific activity, has been provided by the applicants’, which would indicate that they had the possession of the claimed genus of polypeptides. The claimed genera of polypeptides and the encoding polynucleotides have widely variable structures and associated functions. As it is discussed above, a minor changes in structure may result in changes affecting function, since, the specification provided no additional information (species/variant/mutant) correlating structure with function, and one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Furthermore, "Possession may not be shown by merely describing how to obtain possession of members of the claimed, genus or how to identify their common structural features" (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895). A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the .gene does (function), rather what it is (structure), see University of California v. Eli Lilly & Co., 43 USPQ2d 1938, thus above claims lack adequate written description.
Applicants' are referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.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:
Claim Rejections, 35 U.S.C 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.
Claims 1-2, 10-12 and 16-20 are rejected under 35 U.S.C. 102(a)(1)
as being anticipated by Manor et al.( WO94/10131,1994, , pp 1-54 ids).
Manor et al.disclose an efficient method of producing phytosphingosine-containing ceramide one having general structure (1), comprising: (a) obtaining a phytosphingosine base from tetraacetylphytosphingosine (TAPS) by 3 deacetylation reaction wherein the TAPS is produced by fermentation of yeast cells of the F-60-10 mating type strain of Hansenula ciferril using a fed-batch mode and a non-fermentable carbon source; and (b) coupling together the phytosphingosine base and a fatty acid/m-hydroxy fatty acid component wherein the m-hydroxy fatty acid component is prepared by a process which includes Kolbé synthesis ( abstract), --reads on claims -1-2, 10-11 and 16 ).
Reference discloses that additionally yields are noted to be improved when the fermentation of Hansenula ciferrii is carried out in the presence of a surfactant. Examples of suitable surfactants are Tween and Triton. The fermentation is therefore preferably conducted in the presence of such surfactants. Furthermore, yields are noted to be improved when the fermentation of Hansenula ciferrii is carried out in the presence of selected precursors e.g. palmitic acid, serine and mixtures thereof. The fermentation is therefore preferably conducted in the presence of such precursors. TAPS is conveniently extracted from the fermentation products by solvent extraction. The fermentation process produces a mixture of products, namely phytosphingesines with some sphingosines, of mixed chain lengths. The main product is TAPS, with some triacetylphytosphingosine and also some triacetylsphingosine. The products are a mixture of C16-20 of odd and even chain length, mainly straight chain but possibly with some branched chain products. The main product is C18 straight chain TAPS.
TAPS can be readily converted to phytosphingosine by a suitable deacetylation reaction, as is well known to those skilled in the field, e.g. by base catalyzed hydrolysis for example using potassium hydroxide. The phytosphingosine obtained via fermentation of Hansenula ciferrii is then used for the preparation of other ( teach claims 1-2, 10-12, 16-20).
Claim Rejections: 35 USC § 103
The following is a quotation of 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.
This application currently names joint inventors. In considering patentability of the claims under 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 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
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 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.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
According to MPEP 2143:"Exemplary rationales that may support a conclusion of obviousness include:(A) Combining prior art elements according to known methods to yield predictable results;(B) Simple substitution of one known element for another to obtain predictableresults;(C) Use of known technique to improve similar devices (methods, or products) in the same way;(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel."
Claims 1-6, 10-18, 20 are rejected under 35 U.S.C. 103 as being unpatentable over Schwab et al.( US PAT 11155841, US20180179563 priority 08/24/2015) in view of Manor et al.(WO/9410131 ids)
Schwab et a. disclosed ( abstract, Para 009-0024) a method for producing an objective substance such as sphingoid bases and sphingolipids using yeast is provided. An objective substance is produced by cultivating yeast having an ability to produce the objective substance in a culture medium containing an additive , such as cyclodextrin and zeolite that is able to associate with, bind to, solubilize, and/or capture the objective substance, and collecting the objective substance from cells of the yeast and/or the culture medium. wherein the objective substance is selected from the group consisting of phytosphingosine (PHS), sphinganine (DHS), phytosphingosine is selected from the group consisting of C16 PHS, C18 PHS, C20 PHS. S Schwab et al. aforementioned method, wherein the activity or activities of the one or more proteins are reduced by attenuating the expression of the respective genes encoding the one or more proteins, or by disrupting the respective genes encoding the one or more proteins. Also Schwab et a. teach the yeast is Saccharomyces cerevisiae.
Schwab et a. also disclosed the yeast has been modified so that the expression and/or activity or activities of one or more proteins selected from proteins encoded by LCB1, LCB2, TSC10, SUR2, SLI1, ATF2, LAG1, LAC1, LIP1, and UGCG genes are increased. ( obvious over applicants claim 1-6, 10-18, 20).
However Schwab et al. silent about adding fatty acid in yeast cell fermentation media.
Manor et al disclosed Manor et al.disclose an efficient method of producing phytosphingosine-containing ceramide one having general structure (1), comprising: (a) obtaining a phytosphingosine base from tetraacetylphytosphingosine (TAPS) by 3 deacetylation reaction wherein the TAPS is produced by fermentation of yeast cells of the F-60-10 mating type strain of Hansenula ciferril using a fed-batch mode and a non-fermentable carbon source; and (b) coupling together the phytosphingosine base and a fatty acid/m-hydroxy fatty acid component wherein the m-hydroxy fatty acid component is prepared by a process which includes Kolbé synthesis.
Manor et al disclose yields are noted to be improved when the fermentation of Hansenula ciferrii is carried out in the presence of a surfactant. The fermentation is therefore preferably conducted in the presence of such surfactants. Furthermore, yields are noted to be improved when the fermentation of Hansenula ciferrii is carried out in the presence of selected precursors e.g. palmitic acid, serine and mixtures thereof. The fermentation is therefore preferably conducted in the presence of such precursors.
Regarding claim 3 none of the teach adding myristic acid C14 long fatty acid is tetradecanoyl fatty acid is myristic acid , CH3(CH2)12COOH. Since Manor et al. teach adding fatty acid like palmitic acid yields are noted to be improved when the fermentation of Hansenula ciferrii is carried out , one of skill in art would try to replace one fatty acid like palmitic acid with other fatty acid, like myristic acid , CH3(CH2)12COOH.
Consequently, It would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was effectively filed to combine the teaching of Schwab et al. and Manor et al. to modify the method of Schwab et al to add yeast cultural media precursors e.g. fatty acids like palmitic acid, and serine. Because Manor et al. noted yields are improved when the fermentation of Hansenula ciferrii yeast is carried out in the presence of selected precursors e.g. palmitic acid, serine and mixtures thereof. One o skilled in art therefore motivated to combine fatty acid in the yeast culture media for the production of phytosphingosine (PHS), sphinganine (DHS).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir.
1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum,
686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321 (c) or 1.321 (d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321 (b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-l.jsp.
Claims 1-6, 10-20 are rejected obviousness double patenting rejection as being unpatentable over claims 1-11 of U.S. Patent 11155841 in view of Manor et al.( WO94/10131,1994, , pp 1-54 ids. Although the claims at issue are not identical, they are not patentably distinct from each other because they are claiming common subject matter, as follows: Claims 1-7, 10-14 of the instant application and claims 1 -11 of the reference patent 11155841 are both directed to a method of producing an objective substance using yeast wherein substance is sphingoid or sphingolipids. However Reference Patent is silent of adding fatty acid in the yeast culture media. Manor et al disclose yields are noted to be improved when the fermentation of Hansenula ciferrii is carried out in the presence of a surfactant. The fermentation is therefore preferably conducted in the presence of such surfactants. Furthermore, yields are noted to be improved when the fermentation of Hansenula ciferrii is carried out in the presence of selected precursors e.g. palmitic acid, serine and mixtures thereof.
Consequently, It would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was effectively filed to combine the teaching of Schwab et al. and Manor et al. to modify the method of Schwab et al to add yeast cultural media precursors e.g. fatty acids like palmitic acid, and serine. Because Manor et al. noted yields are improved when the fermentation of Hansenula ciferrii yeast is carried out in the presence of selected precursors e.g. palmitic acid, serine and mixtures thereof. One of skilled in art therefore motivated to combine fatty acid in the yeast culture media for the production of phytosphingosine (PHS), sphinganine (DHS).
Td is needed to overcome the above ODP rejection..
Conclusion
Claims 1-6, 10-20 are rejected and no claim is allowable.
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/MOHAMMAD Y MEAH/Examiner, Art Unit 1652
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