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 Response of 5 May 2026 has been entered.
Claims 16-18 and 24-42 are currently pending.
Any rejection of objection not reiterated herein has been withdrawn.
Response to Arguments
Applicant's arguments filed 5 May 2026 have been fully considered but they are not persuasive.
Applicant argues that the disclosure in the specification of SEQ ID 2 along with the description/definition of sequence identity (Spec., p. 7) provides for a precise definition of the claimed subject matter sufficient to distinguish it from other materials. This is not persuasive because, while the specification describes various genera of peptides based on structural similarity to SEQ ID 2 (80% identity as in claim 16, or having 1, 2, 3, or 4 alterations as in claims 39-42), the claims are directed to a "signal peptide", which is defined in the specification as "amino acid sequences present in the amino terminus of many newly synthesized polypeptides that target these into or across cellular membranes" (Published Spec. US20260117210, [0004]). Thus, the claims are effectively drawn to a subgenus of peptides capable of functional as a signal peptide within the claimed genera relating to SEQ ID 2. The written description requirement requires that the specification evidences possession of the subgenus, e.g. by disclosure of relevant, identifying characteristics and/or by functional characteristics coupled with a known or disclosed correlation between function and structure (MPEP 2163). A “representative number of species” means that the species which are adequately described are representative of the variation within the genus, and the disclosure of only a single species within a genus is generally insufficient where the unpredictability in the art is such that one of ordinary skill could not predict the operability of other species than the one disclosed (MPEP 2163). The instant specification discloses only the species of SEQ ID 2, and does not provide any other guidance such as a structure-function relationship that would allow one of ordinary skill in the art to identify additional signal peptides from the describes genera. Moreover, the DUF3298 domain-containing polypeptide from which SEQ ID 2 is derived has an unknown function (Spec., p. 5, lines 5-13), and thus the identification of additional signal peptides within the claimed genera would have been unpredictable. Finally, the instant claims are not similar to situations where one species has been found to adequately support a genus, such as where the genus relates to a functionally unimportant or auxiliary aspect of the invention or where the specification provides other means of identifying members of the genus (see MPEP 2163, II., A., 3., ii.).
Applicant further argues that Caspers (relied on in the written description rejection to evidence unpredictability in the art of signal peptides) predates the instant application by ten years. This is not persuasive because the evidence of Caspers regarding the general lack of a defined relationship between signal peptide sequences and functionality is consistent with the statement in the specification 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). Such evidence, together with the fact that the DUF3298 domain-containing polypeptide from which the claimed signal peptide is derived has a unknown function, is sufficient to reasonably establish unpredictability in the relevant art. Applicant has not provided any evidence rebutting the finding of unpredictability.
Applicant further argues that Caspers teaches that mutations in the signal peptide mostly did not significantly change cutinase activity. This is not persuasive to overcome the written description rejection because the mutational study of Caspers was conducted on a signal peptide distinct from that instantly claimed and the specific findings related to such peptide would thus not be attributable to the claimed invention. Moreover, the analysis of Caspers involved mutation of only a single amino acid at a time within a limited 5-residue segment of the signal peptide (residues 2-7), and the analysis did in fact reveal a large proportion of species having significantly reduced activity (see Fig. 1B).
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 16-18, 25-34 and 36-42 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 80% sequence identity to SEQ ID 2 (claims 16-18, 24-34, 36 and 37) or has 1, 2, 3, or 4 alterations with respect to SEQ ID 2 (claims 39-42). The specification defines "signal peptide" as "amino acid sequences present in the amino terminus of many newly synthesized polypeptides that target these into or across cellular membranes" (Published Spec. US20260117210, [0004]). The specification further states that 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 the claims allow for alterations of any kind along any residue of the sequence (e.g., the 80% (or 65%) identity limitation allows for 5 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 up to 5 positions at any point along the length of the sequence).
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) (indefiniteness)
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 35 is 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 35 depends from claim 19, which has been cancelled. The scope of claim 35 is thus unclear (it is unclear which bacterial host cell is being referred to).
Allowable Subject Matter
Claim 24 is 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
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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
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