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 371 of PCT/EP2022/067738, filed on 01/08/2024.
Claims 1-11, 13, and 14-15 are currently pending in the instant application.
The preliminary amendment filed on 01/08/2024, amending claims 4-7, 9 and 13, canceling claims 12, and adding new claims 14-15 is acknowledged.
Election/Restriction
Applicant's election without traverse of species E40-encoded by the polynucleotide sequence of SEQ ID NO: 6, the expression cassette of SEQ ID NO: 21 in the response filed on 07/21/2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-11 and 13-15 are present for examination.
Priority
Acknowledgement is made of applicants claim for foreign priority under 35 U.S.C. 119(a)-(d) to a foreign patent application ITALY 102021000018254, filed on 07/07/2021 with English translation. The Examiner also acknowledging the filing of PCT/EP2022/067738, filed on 06/28/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/08/2024 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. 1, 2, 3, 6, 5, 6, 7 and 8). 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. 1, 2, 3, 6, 5, 6, 7 and 8 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, 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. 1, 2, 3, 6, 5, 6, 7 and 8 in the Drawings). See particularly 37 CFR 1.821(d).
Appropriate correction is required.
Drawings Objections
Drawings submitted on 01/08/2024 are not accepted by the Examiner because Fig. 1, 2, 3, 6, 5, 6, 7 and 8 in drawings are not compliance to the sequence rule. Appropriate correction is required.
Claim Objections
Claims 1, 2, 4 7, 11 are objected to in the recitation “TK24”, “SR40”, “E40”, “KasO”, “vsi”, “attB”; as abbreviations should not be used without at least once fully setting forth what they are used for. Appropriate correction is required.
Claims 1, 4- 6, and 8 are objected to in the recitation “sequence”, which should be changed to “the sequence”. 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:
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 of carrying out his invention.
Claims 10-11 are rejected under 35 U.S.C. 112(a), as failing to comply with the enablement requirement. The claim(s) contains 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.
The invention appears to employ novel microorganisms (RedStrep 1.3, 1.6, 1.9, DSM 33930, or DSM 33931). Since the microorganisms are essential to the claimed invention, they must be obtainable by a repeatable method set forth in the specification or otherwise be readily available to the public. The recited microorganisms have not been shown to be publicly known and freely available. The enablement requirements of 35 U.S.C. 112 may be satisfied by a deposit of the microorganisms. The specification does not disclose a repeatable process to obtain the microorganisms and it is not apparent if the microorganisms are readily available to the public. Accordingly, it is deemed that a deposit of these plasmids should have been made in accordance with 37 CFR 1.801-1.809.
It is noted that applicants have deposited some of the organisms but there is no indication in the specification as to public availability. If the deposit was made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants, or a statement by an attorney of record over his or her signature and registration number, stating that the specific strain has been deposited under the Budapest Treaty and that the strain will be available to the public under the conditions specified in 37 CFR 1.808, would satisfy the deposit requirement made herein.
If the deposit has not been made under the Budapest treaty, then in order to certify that the deposit meets the criteria set forth in 37 CFR 1.801-1.809, applicants may provide assurance or compliance by an affidavit or declaration, or by a statement by an attorney of record over his or her signature and registration number, showing that:
1. during the pendency of this application, access to the invention will be afforded to the Commissioner upon request;
2. upon granting of the patent the strain will be available to the public under the conditions specified in 37 CFR 1.808;
3. the deposit will be maintained in a public repository for a period of 30 years or 5 years after the last request or for the effective life of the patent, whichever is longer; and
4. the deposit will be replaced if it should ever become unavailable.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 2-3 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 2 is indefinite in the recitation of “biologically active fragment ” in the context of E40 protein, as it is unclear what the scope of activities that is encompassed by this term includes. At page 8 of the specification characterize the term “biologically active fragment” of naturally occurring E40 protein as portion of the endopeptidase, which maintain its specific glutenase activity. As the number of naturally occurring molecules is vast, and the scope of possible structural, or biochemical functions is even broader with no clear boundaries of what these terms include, the scope of “biologically active fragments” of E40 is vague and indefinite.
Claims 2-3 are rejected under 35 U.S.C. 112(b), as being indefinite and vague for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. In the present instance, claim 2 recites the broad recitation 60%, and the claim also recites 70, 80, 90, or 95%, which is the narrower statement of the range/limitation.
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, 2, 6-9, 10-11, and 13-15 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.
Claim 1 is directed to a recombinant vector for heterologous expression of a recombinant protein in a Streptomyces host cell bearing an expression cassette comprising: a promoter, a regulatory element, and a polynucleotide encoding a recombinant protein operably linked to said promoter and regulatory element; wherein: - said promoter is an engineered kasO promoter (kasOp*) having sequence SEQ ID NO: 10; - said regulatory element is an optimized synthetic SR40 ribosome-binding site (RBS) having sequence SEQ ID NO: 11; - the polynucleotide encoding for the recombinant protein of interest encodes for a recombinant protein that includes a N-terminal signal peptide; and - the recombinant vector is a single-site integrating vector. Claim 2 is drawn to a recombinant vector of claim 1, wherein the recombinant protein is an Actinoallomurus endopeptidase of sequence comprising or consisting of SEQ ID NO: 1; a biologically active fragment of E40; a naturally occurring allelic variant of E40; or an endopeptidase of sequence having at least 60%, 70%, 80%, 90% or 95% of identity to SEQ ID NO: 1
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 any recombinant vector for heterologous expression of any recombinant protein derived from any source having no structural feature, in a Streptomyces host cell bearing any expression cassette comprising: any promoter, any regulatory element, and any polynucleotide encoding any recombinant protein derived from any source having no structural feature operably linked to said promoter and regulatory element; wherein: - said promoter is an engineered kasO promoter (kasOp*) having sequence SEQ ID NO: 10; - said regulatory element is an optimized synthetic SR40 ribosome-binding site (RBS) having sequence SEQ ID NO: 11; - the polynucleotide encoding for the recombinant protein of interest encodes for a recombinant protein that includes a N-terminal signal peptide; and - the recombinant vector is a single-site integrating vector, wherein the recombinant protein is an Actinoallomurus endopeptidase of sequence comprising or consisting of SEQ ID NO: 1; any biologically active fragment of E40; a naturally occurring allelic variant of E40; or any endopeptidase of sequence having at least 60%, 70%, 80%, 90% or 95% of identity to SEQ ID NO: 1, i.e., 40% non-identity to SEQ ID NO: 1, that encompasses many mutants, many variants of endopeptidase 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., lipase variant 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) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
Claims are drawn to very broadly any recombinant vector for heterologous expression of any recombinant protein derived from any source having no structural feature, in a Streptomyces host cell bearing any expression cassette comprising: any promoter, any regulatory element, and any polynucleotide encoding any recombinant protein derived from any source having no structural feature operably linked to said promoter and regulatory element; wherein: - said promoter is an engineered kasO promoter (kasOp*) having sequence SEQ ID NO: 10; - said regulatory element is an optimized synthetic SR40 ribosome-binding site (RBS) having sequence SEQ ID NO: 11; - the polynucleotide encoding for the recombinant protein of interest encodes for a recombinant protein that includes a N-terminal signal peptide; and - the recombinant vector is a single-site integrating vector, wherein the recombinant protein is an Actinoallomurus endopeptidase of sequence comprising or consisting of SEQ ID NO: 1; any biologically active fragment of E40; a naturally occurring allelic variant of E40; or any endopeptidase of sequence having at least 60%, 70%, 80%, 90% or 95% of identity to SEQ ID NO: 1, i.e., 40% non-identity to SEQ ID NO: 1, that encompasses many mutants, many variants of endopeptidase enzymes derived from many unknown sources and many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, any variant of a parent lipase, wherein said variant has: a) at least 80% but less than 100% sequence identity (for claim 18), and comprises a substitution corresponding to F51I in SEQ ID NO: 2, i.e., 20% non-identity to SEQ ID NO: 2, that encompasses many variant lipase enzymes derived from many unknown sources and many mutants, variants, and fragments thereof, which can have wide variety of unknown structures, which can have wide variety of unknown structures, whose structures are not fully described in the specification. No information, beyond the characterization of variant endopeptidases 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 variant endopeptidase enzymes, within the scope of the claimed genus. The genus of polypeptides claimed is a large variable genus including many mutants, variant and fragments thereof, which can have wide variety of structures. Therefore, many structurally unrelated enzymes (variant endopeptidase) 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.
Conclusion
Status of the claims:
Claims 4 and 5 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 1-2, 3, 6-11, and 13-15 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, 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
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