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
The Preliminary Amendment of 18 Dec. 2023 has been entered.
Claims 16-34 are currently pending.
Claim Objections
Claims 21 and 26 are objected to because of the following informalities:
Claim 21 should be amended to delete “6.” and as follows: “the signal peptide
Claim 26 should be amended as follows: “wherein the polypeptide having cutinase activity is a bacterial polypeptide”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a) (written description)
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 16-21, 23 and 25-34 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to a nucleic acid construct comprising a first sequence encoding a signal peptide operably linked to a second sequence encoding a polypeptide having cutinase activity, wherein the signal peptide has at least 60% sequence identity to SEQ ID 2 (or 65% in the case of claim 23). According to the specification, the “present invention is based on the surprising and inventive finding that expression of several cutinases with a signal peptide (SP32) obtained from a bacterial DUF3298 domain-containing polypeptide provides an improved yield of the cutinases compared to expression of the same cutinases with other signal peptides, i.e. a 2.2-fold to 4.6-fold increase in cutinase expression” (Spec., p. 2, lines 18-20). SEQ ID 2 is a 28-amino acid sequence, and thus the 60% (or 65%) identity limitation allows for 11 (or 9 in the case of 65% identity) mismatched amino acids, that can be any amino acid at any point along the 28-amino acid sequence. Moreover, the specification defines sequence identity as the longest identity between two sequences excluding gaps (Spec., p. 7, lines 19-22). The claimed signal peptide thus includes longer sequences that include a shorter stretch having the claimed identity to SEQ ID 2, such as the 225-amino acid polypeptide of SEQ ID 4 in dependent claim 22. Thus, the instant claims encompass a large genus of signal polypeptides.
To show possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus, which in the case of a chemical invention such as a polypeptide requires a precise definition, such as by structure, formula, chemical name, or physical properties (MPEP 2163). The requirement may be satisfied through sufficient description of a representative number of species 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 (MPEP 2163). For inventions in an unpredictable art, adequate written description of a genus embracing widely variant species cannot be achieved by disclosing only one species within the genus (MPEP 2163, II. 3.).
The instant specification discloses the signal peptide of SEQ ID 2 as the only disclosed species within the claimed genus. While Example 8 of the specification describes production of a library of signal peptide sequences (referred to as SP1 to SP85, where SP32 is SEQ ID 2), the specification does not disclose any amino acid sequences other than SEQ ID 2 (the sequences of SP1-SP31 and SP33-SP85 are not disclosed), and does not provide any other identifying characteristics for the tested peptides nor any relationship (e.g., sequence identity) between such peptides and SEQ ID 2. The specification also fails to provide any other teachings or guidance that would allow one of ordinary skill in the art to identify additional species within the claimed genus, such as a structure-function relationship identifying which portions of SEQ ID 2 can be modified, which types of modifications would be suitable and/or which portions are critical for its functionality as a signal peptide. A sequence search of the prior art reveals that at the time of filing only two sequence variants of the signal peptide from the DUF3298 domain-containing polypeptide of Bacillus pumilus, from which SEQ ID 2 is derived, were known – a variant with an M8T substitution (e.g., Accession A0A2A5INW4_BACPU in the us-18-571-661-2.rup file) and a variant with M8T and A27V substitutions (A0A081LAC8_9BACI in us-18-571-661-2.rup). These two variants are not representative of the variability within the claimed genus. The specification further provides that it is difficult to predict the functionality of any given signal peptide for production of a particular enzyme (Spec., p. 1, line 27 to p. 2, line 2), and that the DUF3298 domain-containing polypeptide from which SEQ ID 2 is derived has an unknown function (Spec., p. 5, lines 5-13). Similarly, Caspers et al., Applied microbiology and biotechnology 86.6 (2010): 1877-1885, evidences that signal peptides do not comprise a recognizable consensus sequence and that in silico prediction of functional signal peptides for a given target protein is not possible (p. 1878, 2nd ¶; see also, p. 1883, last ¶ to p. 1884, 1st ¶ - “at the present time, it is still not possible to predict the effects of certain amino acid exchanges in a specific SP in combination with a selected target protein”). Thus, the specification describes an unpredictable art along with a single amino acid sequence within the claimed genus of signal peptides, and does not provide any additional teachings or guidance that would allow one of ordinary skill to identify additional species within the genus. While the specification describes a general methodology that could potentially be used to identify variants of SEQ ID 2 (e.g. using mutagenesis and screening procedures, such as taught by Caspers) (Spec., p. 10, lines 3-25), adequate written description of a chemical invention requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the claimed invention (MPEP 2163, II. 3.). For example, Caspers teaches that due to the unpredictability of the art, a mutagenesis and screening process to discover signal peptide variants for cutinase expression required generating and testing variants of all possible residues at each position (e.g., under Results). The mutagenesis also resulted in numerous clones having essentially no secretory activity (Fig. 1b), even though tested variants were mutated at only a single position of the signal peptide (in contrast, the claims encompass variants differing at 9-11 positions at any point along the length of the sequence). Regarding dependent claim 19, the specification defines the term “variant” as “a signal peptide … comprising a substitution, an insertion (including extension), and/or a deletion (including truncation), at one or more positions compared to the parent” (Spec., p. 8, lines 5-11). Since there is no limit to the extent of insertions, substitutions and deletions in the claimed variants, claim 19 does not effectively limit the size of the claimed genus of signal peptides. Regarding claim 20 (wherein the signal peptide is “from a DUF3298-containing polypeptide expressed by a Bacillus species”), the specification does not expressly define the term “from a DUF3298-containing polypeptide” but defines the similar terms “obtained” or “derived” as meaning “the molecule originally has been isolated from the given source and that the molecule can either be utilized in its native sequence or that the molecule is modified by methods known to the skilled person” (Spec., p. 6, lines 29-33). Since there are no limits on the extent of such modifications, claim 20 also fails to effectively limit the size of the claimed genus. Regarding claim 21, SEQ ID 4 is a 225-amino acid protein which comprises SEQ ID 2 as the first 28-amino acids. Since the claimed 80% identity could occur at any point along the sequence, the 80% identity limitation does not effectively limit the genus of signal peptide sequences beyond the 60% identity limitation of claim 1.
In light of the above, the claims do not provide adequate written description support for the genus of signal peptides encompassed by claims 16-21, 23 and 25-34.
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.
Claims 33 and 34 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 33 recites cultivating “under conditions conducive for production of the polypeptide having cutinase activity”. The term “conducive” in claim 33 is a term of degree which renders the claim indefinite. The term “conducive” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As a result, one of ordinary skill would not be able to reasonably ascertain whether a particular set of conditions are “conducive” for production. The rejection can be overcome by amending as follows: “under conditions effective for production of the polypeptide having cutinase activity”.
Allowable Subject Matter
Claims 22 and 24 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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT J YAMASAKI whose telephone number is (571)270-5467. The examiner can normally be reached M-F 930-6 PST.
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657