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
Application Status
This application is a Non-Provisional patent application filed on 01/13/2025.
Claims 1-17 are currently pending in the instant application.
Election/Restriction
Applicant's election without traverse of Group I, Claims 1-9, drawn to a non-naturally occurring Clostridium thermocellum comprising an exogenous gene encoding for β-xylosidase wherein the Clostridium thermocellum metabolizes cellulose and xylan to xylose in the response filed on 08/27/2026 is acknowledged.
Claims 10-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicants request for rejoinder is noted. However, current claims of elected Group I are not allowable at this time. When Group I would be allowable, rejoinder request would be evaluated at that time.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-9 are present for examination.
Priority
Acknowledgement is made of applicants claim for priority of US Provisional application 63/620,497, filed on 01/12/2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/04/2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is considered by the examiner. The signed copy of 1449 is enclosed herewith.
Drawings objections-Non-Compliance of Sequence Rule
The disclosure is objected to because of the following informalities:
2422.01-.04 The Requirement for Exclusive Conformance; Sequences Presented
in the Drawing Figures (see, Fig.10 and 11). 37 CFR 1.821(b) requires….Any sequence more than 10 nucleotides or more than 3 amino acids, regardless of the format or the manner of presentation of that sequence in the Claims, Specification or Drawings the sequence must still be included in the Sequence Listing and the sequence identifier (“SEQ ID NO:X”) must be used (see, Fig. 10 and 11 in the Drawings). It should be noted, though, that when a sequence is presented in a drawing, regardless of the format or the manner of presentation of that sequence in the drawing, more than 10 nucleotides or more than 3 amino acids, regardless of the format or the manner of presentation of that sequence in the Claims, Specification or Drawing the sequence must still be included in the Sequence Listing and the sequence identifier (“SEQ ID NO:X”) must be used (see, Fig. 510 and 11 in the Drawings). See particularly 37 CFR 1.821(d).
Appropriate correction is required.
Drawings
Drawings submitted on 01/13/2025 are not accepted by the Examiner because of non-compliance of the sequence rule. Appropriate correction is required.
Claim Objections
Claims 2-8 are objected to in the recitation “xylA”, “xylB”, and “xylD”; as abbreviations should not be used without at least once fully setting forth what they are used for. Appropriate correction is required.
Claim Rejections - 35 USC § 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.
A. Written Description
Claims 1-9 are rejected under 35 U.S.C. 112(a), 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.
Claims are directed to a non-naturally occurring Clostridium thermocellum comprising an exogenous gene encoding for β-xylosidase wherein the Clostridium thermocellum metabolizes cellulose and xylan to xylose, wherein the endogenous xylA and xylB genes are about 70% identical to SEQ ID NO: 1-2 of the instant application, and the exogenous xylD gene, which is about 70% identical to SEQ ID NO: 3 that derived from any unknown sources wherein the genes encompass many such genes and many mutants, variants and fragments thereof in the context of 70% identity, i.e., 30% non-identity.
The Court of Appeals for the Federal Circuit has 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).
Thus, Claims are drawn to a non-naturally occurring Clostridium thermocellum comprising an exogenous gene encoding for β-xylosidase wherein the Clostridium thermocellum metabolizes cellulose and xylan to xylose, wherein the endogenous xylA and xylB genes are about 70% identical to SEQ ID NO: 1-2 of the instant application, and the exogenous xylD gene, which is about 70% identical to SEQ ID NO: 3 that derived from any unknown sources wherein the genes encompass many such genes and many mutants, variants and fragments thereof in the context of 70% identity, i.e., 30% non-identity to SEQ ID NO: 1, 2 and 3, that encompasses many mutants, variants, and many fragments of said β-xylosidase enzymes comprising xylA, xylB and xylD genes encoding β-xylosidase enzymes derived from many unknown sources and many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, i.e. No Structure-Function correlation, which is required to fulfill the Written Description (WD) requirement.
As discussed in the written description guidelines the Written Description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. A representative number of species means that the species, which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Furthermore, the genus of polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides are adequately described by the disclosure of the structures of prior art. However, the art clearly teaches the “Practical Limits of Function Prediction”: Whisstock et al., (2003) 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, it is difficult to state criteria for successful prediction of function, since function is a vague concept. 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., (1999) teaches that one conservative amino acid substitution transforms a -ketoacyl synthase into a malonyl decarboxylase and completely eliminates -ketoacyl synthase activity. Similarly, the art also teaches that functionally similar molecules have different structures; Kisselev L., (2002) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
Furthermore, the genus of polynucleotide encoding polypeptides or variants required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides are adequately described by the disclosure of the structures of prior art, i.e., β-xylosidase enzymes. However, the art clearly teaches the “Practical Limits of Function Prediction”: Whisstock et al., (2003) 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, it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. 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., (1999) teaches that one conservative amino acid substitution transforms a -ketoacyl synthase into a malonyl decarboxylase and completely eliminates -ketoacyl synthase activity. Similarly, the art also teaches that functionally similar molecules have different structures; Kisselev L., (2002) teaches that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
Claims 1-5 are drawn to very broadly a non-naturally occurring Clostridium thermocellum comprising an exogenous gene encoding for β-xylosidase wherein the Clostridium thermocellum metabolizes cellulose and xylan to xylose, wherein the endogenous xylA and xylB genes are about 70% identical to SEQ ID NO: 1-2 of the instant application, and the exogenous xylD gene, which is about 70% identical to SEQ ID NO: 3 that derived from any unknown sources wherein the genes encompass many such genes and many mutants, variants and fragments thereof in the context of 70% identity, i.e., 30% non-identity to SEQ ID NO: 1, 2 and 3, that encompasses many mutants, variants, and many fragments of said β-xylosidase enzymes comprising xylA, xylB and xylD genes encoding β-xylosidase enzymes derived from many unknown sources and many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, whose structures are not fully described in the specification. No information, beyond the characterization of few genes of xylA, xylB and xylD encoding β-xylosidase enzymes has been provided, which would indicate that applicants had possession of the claimed genus. The specification does not contain sufficient disclosure of the structure with function of all the genes encoding β-xylosidase enzymes, within the scope of the claimed genus. The genus of polypeptides claimed is a large variable genus including many mutants, variants and fragments thereof, which can have wide variety of structures. Therefore, many structurally unrelated enzymes (β-xylosidase enzymes) within the scope of these claims. The specification discloses the structure of only few representative species of the claimed genus, which is insufficient to put one of skill in the art in possession of the attributes and features of all species within the claimed genus. Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed.
Applicant is 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.
Claim Rejections - 35 U.S.C. § 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 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 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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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 predictable
results;
(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 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Shao et al. (Characterization of a Novel _-Xylosidase, XylC, from Thermoanaerobacterium saccharolyticum JW/SL-YS485. Appl and Environ Microbiol (2011); 77(3): 719-726) in view of Argyros et al. (Genetically modified Clostridium thermocellum engineered to ferment xylose. WO 2012/088467A2, publication 06/28/2012, see IDS).
The Broadest Reasonable Interpretation (BRI) of claims 1-5, which are drawn to Claims 1-5 are drawn to very broadly a non-naturally occurring Clostridium thermocellum comprising an exogenous gene encoding for β-xylosidase wherein the Clostridium thermocellum metabolizes cellulose and xylan to xylose, wherein the endogenous xylA and xylB genes are about 70% identical to SEQ ID NO: 1-2 of the instant application, and the exogenous xylD gene, which is about 70% identical to SEQ ID NO: 3 that derived from any unknown sources wherein the genes encompass many such genes and many mutants, variants and fragments thereof in the context of 70% identity, i.e., 30% non-identity to SEQ ID NO: 1, 2 and 3, that encompasses many mutants, variants, and many fragments of said β-xylosidase enzymes comprising xylA, xylB and xylD genes encoding β-xylosidase enzymes derived from many unknown sources and many mutants, variants, and fragments thereof.
Regarding claims 1-9, Shao et al. teach characterization of a Novel beta-Xylosidase XylC, (encoding beta-xylosidase, which is equivalent to xylD as claimed) from Thermoanaerobacterium saccharolyticum JW/SL-YS485, which is 100% identical to SEQ ID NO: 3 of the instant applicationand. Shao et al. further teach The 1,914-bp open reading frame of xylC from Thermoanaerobacterium saccharolyticum JW/SL-YS485 encodes a calculated 73-kDa _-xylosidase, wherein XylC, different from any other glycosyl hydrolase in the database and representing a novel glycohydrolase family, and hydrolysis occurred under retention of the anomeric configuration, and trans glycosylation occurred in the presence of alcohols as acceptors, wherein with the use of vector pHsh, expression of XylC, the third -xylosidase in this bacterium, increased approximately 4-fold when a loop within the translational initiation region in the mRNA was removed by site-directed mutagenesis, and the express of the increased expression of xylCm is due to removal of a stem-loop structure without a change of the amino acid sequence of the heterologous expressed enzyme (XylCrec) in Escherichia coli as exogenous and heterologous expression. Shao et al. also teach endogenous xylA and xylB expression, which are at least 90% identity to SEQ ID NO: 1 and 2 of the instant application, and when gel filtration was applied, purified XylC had molecular masses of 210 kDa and 265 kDa using native gradient gel electrophoresis. The protein consisted of 78-kDa subunits based on SDS gel electrophoresis and contained 6% carbohydrates. XylC and XylCrec exhibited maximum activity at 65°C and pH65°C 6.0, a 1-h half-life at 67°C, a Km for p-nitrophenyl-_-D-xyloside of 28 mM, and a Vmax of 276 U/mg and retained 70% activity in the presence of 200 mM xylose, suggesting potential for industrial applications. (see, Title, abstract, pg721, left Col, para 3-8, Table 2, and Fig. 1-4).
Claim 9 is included in this rejection because “reduce xylan degradation intermediates xylose and xylobiose” is the inherent property of the beta-Xylosidase of Shao et al.
Because the beta-xylosidase enzyme of the claimed invention and that the beta-xylosidase enzyme of the reference is one and the same, Examiner takes the position that the “reduce xylan degradation intermediates xylose and xylobiose” disclosed in the reference inherently associated with the beta-xylosidase enzyme as claimed in claim 9. Since the Office does not have the facilities for examining and comparing applicants' protein with the protein of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product (i.e., beta-xylosidase or xylan, xylose or xylobiose) and the product of the prior art (i.e., beta-xylosidase or xylan, xylose or xylobiose). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Shao et al. do not teach using Clostridium thermocellum as a host cell.
However, Argyros et al. teach genetically modified Clostridium thermocellum engineered to ferment xylose portion of biomass (Xylo oligosaccharide), and further teach industrial bioconversion of the xylose portion of biomass materials into fuels and chemicals, wherein industrial bioconversion of the xylan portion of biomass materials into fuels and chemicals, wherein the bacterium is Clostridium thermocellum, a highly cellulolytic organism that has much potential as a biocatalyst in a consolidated bioprocess configuration for genetic modification that confers the ability to ferment xylose oligosaccharide to D-xylose monomer using C. thermocellum expressing beta-xylosidase, and the strains created with this modification, wherein the genetic modification is composed of two genes contained in an operon from T. saccharolyticum as claimed wherein the genes express proteins with xylose isomerase (XI= SEQ ID NO: 1=xylA) and xylulokinase activates (XK= SEQ ID NO: 2= xylB), which are at least 90% identity to SEQ ID NO: 1 and 2 of the instant application, wherein the invention relates to a recombinant Clostridium thermocellum host cell capable of fermenting xylan, wherein the recombinant Clostridium thermocellum a host cell comprising one or more heterologous polynucleotides encoding one or more enzymes capable of metabolizing xylose, wherein Clostridium thermocellum host cell comprises a heterologous polynucleotide that encodes a xylose isomerase (XI) as well as xylulo kinase (XK), wherein said one or more heterologous polynucleotides are derived from Thermoanaerobacterium saccharolyticum, which are same genes of T. saccharolyticum as claimed, wherein the one or more heterologous polynucleotides are expressed, wherein expression of the one or more heterologous polynucleotides confers to the recombinant host cell the ability to ferment xylose, wherein the one or more heterologous polynucleotides encoding one or more enzymes is contained in an operon that beta-glycosidase, xylA (XI), and xylB (XK), wherein said host cell T. saccharolyticum ferments xylose to ethanol (Title, abstract, para 9-12, 13-23, 71, 92-94, 97, 101-103, 112-114, Table 1, and claims 1-82,
Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the claimed invention as a whole before the effective filing date, of the invention was made by combining the teachings of Shao et al. and Argyros et al. to use Clostridium thermocellum as a host cells instead of E. coli as taught by Argyros et al., and modify Shao et al. to express all the cellulolytic metabolizing genes including xylA, xylB and xylC encoding beta-xylosidase for fermenting xylose to ethanol by using C. thermocellum as a host cell to arrive the claimed invention.
One of ordinary skilled in the art would have been motivated to use Clostridium thermocellum to express genes of xylA, xylB and xylC (xylD) derived from Thermoanaerobacterium saccharolyticum to overexpress said genes in order to ferment lignocellulosic biomass produced xylose for producing ethanol by fermentation, which is commercially, industrially , and financially beneficial.
One of ordinary skilled in the art would have a reasonable expectation of success because Shao et al. and Argyros et al could successfully produce valuable fermentation product from lignocellulosic biomass.
Thus, the above references render the claims prima facie obvious to one of ordinary skill in the art.
Conclusion
Status of the claims:
Claims 1-9 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IQBAL H CHOWDHURY whose telephone number is (571)272-8137. The examiner can normally be reached on M-F, at 9:00-5:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Iqbal H. Chowdhury, Ph.D.
Primary Patent Examiner
Art Unit 1656 (Recombinant Enzymes and Protein Crystallography)
US Patent and Trademark Office
Ph. (571)-272-8137 and Fax (571)-273-8137
/IQBAL H CHOWDHURY/
Primary Examiner, Art Unit 1656
Prosecution Insights