DETAILED ACTION
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 .
Response to Amendment
Applicant’s amendment filed 01/23/2026 is acknowledged. Claims 27, 31, 37, 51 and 55 are amended and claims 29, 30, 35, 53, 54 and 59 are newly canceled. Claims 27, 28, 31-34, 36, 37, 51, 52, 55-58 and 60 are under examination.
Sequence Rules
This application now complies with the requirements of 37 CFR 1.821 through 1.825 and MPEP 2422.04 because a sequence identifier (“SEQ ID NO: X”) is used in the amendment to Figures 3C, 9C, 12C, 14C, 15C, 27B and 28B filed 01/23/2026.
Specification
The objection to the title of the invention for not being descriptive is withdrawn in response to Applicant’s amendment of the title to read: AtaA Fragment with an Adhesive Property and Reduced Self-aggregation.
Rejections Withdrawn
Any previous rejections over claims 29, 30, 35, 53, 54 and 59 are withdrawn in response to Applicant’s cancelation of those claims.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 27, 28, 31, 37 and 55 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in response to Applicant’s amendment of the claims. Specifically, independent claims 27 and 37 have been amended to define the “functionality-imparting entity” to comply with MPEP 2173.05(g). Further, claim 37 part (ii) has been amended to clearly define that the polypeptide is not AtaA, as suggested at p. 6 of the Office action mailed 09/24/2025.
New Objection/Rejections Maintained
Claim Objections
Claims 27 and 37 are objected to because of the following informalities. The amendment to claims 27 and 37 add the following wherein clause: “wherein the polypeptide comprises an amino acid sequence having at least 80% identity to an amino acid sequence of amino acid positions 2-257 of SEQ ID NO: 1 and does not comprises an amino acid sequence corresponding to an amino acid sequence of amino acid positions 2855-3093 of SEQ ID NO: 1”, which contains a grammatical error and is redundant. The clause should be amended to recite: “wherein the polypeptide comprises an amino acid sequence having at least 80% identity to
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.
The following is a quotation of the first paragraph of pre-AIA 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.
Enablement
The rejection of claims 27, 28, 31-34, 36, 37, 51, 52, 55-58 and 60 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is maintained for reasons of record and the following. The amendment addresses the issue with regard to the functionality-imparting entities and clearly defines the second substance as comprising a support. Nevertheless, Applicant’s amendment to independent claims 27 and 37 still encompasses an amino acid sequence having only 80% identity to residues 2-257 of SEQ ID NO: 1 or a variant sequence thereof wherein the polypeptide does not have a self-aggregation property and has an adhesive property. Further, since claims 27 and 37 recite “a polypeptide which comprises a fragment of the amino acid sequence set forth in SEQ ID NO: 1 or a variant sequence thereof, wherein the polypeptide comprises an amino acid sequence having at least 80% identity to an amino acid sequence of amino acid positions 2-257 of SEQ ID NO: 1”, the fragment and variant of the polypeptide need not comprise residues 2-257 of SEQ ID NO: 1. In other words, Applicant’s amendment defines the polypeptide, not the fragment or variant to which the claim is drawn. Further, the recitation of “an amino acid sequence that is different from the amino acid sequence of AtaA” in claim 37 still represents a large genus of proteins.
Response to Arguments
Applicant argues at p. 11 of the Remarks filed 01/23/2026, 1st paragraph that the amendment “correspond[s] directly to the region the examiner refers to as being supported by the experimental evidence”.
This argument has been fully considered, but is not found persuasive. As noted above, since claims 27 and 37 recite “a polypeptide which comprises a fragment of the amino acid sequence set forth in SEQ ID NO: 1 or a variant sequence thereof, wherein the polypeptide comprises an amino acid sequence having at least 80% identity to an amino acid sequence of amino acid positions 2-257 of SEQ ID NO: 1”, the fragment and variant of the polypeptide need not comprise residues 2-257 of SEQ ID NO: 1. In other words, Applicant’s amendment defines the polypeptide, not the fragment or variant to which the claim is drawn.
The instant specification defines fragments at paragraph [0042]:
As used herein, “fragment” refers to a polypeptide or polynucleotide with a sequence length of 1 to n-1 with respect to a full-length polypeptide or polynucleotide (with the length of n). The length of the fragment can be varied as appropriate according to the objective thereof, and the lower limit of the length thereof, in the case of polypeptides, includes, for example, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50 and more amino acids; and lengths represented by integers not specifically listed here (e.g., 11) can also be appropriate as lower limits. A fragment of the polypeptide of the present disclosure consists of preferably 237 or more and 3364 or less amino acids and more preferably 256 or more and 2846 or less amino acids. Examples of the lower limit include, but are
not limited to, 237 amino acids, 256 amino acids, 300 amino acids, 400 amino acids, 500 amino acids, 600 amino acids, 700 amino acids, 800 amino acids, 900 amino acids, 1000 amino acids, and the like. Examples of the upper limit include but are not limited to, 1000 amino acids, 1100 amino acids, 1200 amino acids, 1300 amino acids, 1400 amino acids, 1500 amino acids, 1600 amino acids, 1700 amino acids, 1800 amino acids, 1900 amino acids, 2000 amino acids, 2100 amino acids, 2200 amino acids, 2300 amino acids, 2400 amino acids, 2500 amino acids, 2600 amino acids, 2700 amino acids, 2800 amino acids, 2846 amino acids, 2900 amino acids, 3000 amino acids, 3100 amino acids, 3200 amino acids, 3300 amino acids, and 3364 amino acids. The length can be any other length, as long as a desired property (e.g., lack of self-aggregation property or maintaining an adhesive property) is maintained.
Even with Applicant’s amendment defining the polypeptide as having 80% identity to an amino acid sequence having residues 2-257 of SEQ ID NO: 1, the specification still encompasses a vast number of fragments. In addition, the claims still recite variants of the fragments of SEQ ID NO: 1, defined at paragraph [0031] of the instant specification:
The “variant”, “derivative”, “analog” or “mutant” (of adhesive polypeptides and the like) as used herein are used interchangeably, and the above terms preferably include molecules including regions that are substantially homologous to the protein (e.g., adhesive polypeptide) of interest, although not intended to be limiting; and in the case of amino acid sequence, nucleic acid sequence (nucleotide sequence, base sequence), such sequences are referred to as “altered sequence”, “derived sequence”, “analogous sequence”, and “mutated sequence”. Such molecules, in various embodiments, are at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% identical, throughout amino acid sequences of the same size, or in comparison with sequences to be aligned by conducting alignment with a computer homology program that is known in the art; or nucleic acids encoding such molecules can hybridize to sequences encoding component proteins under (highly) stringent, moderately stringent, or non-stringent conditions. This means that each is a product of protein alteration by amino acid substitutions, deletions and additions, in which the variant or derivative thereof still exhibits the biological function of the original protein, but not necessarily to the same degree. The variant may have a sequence that is preferably 70% or more identical, more preferably 80% or more identical, even more preferably 90% or more identical, still even more preferably 95% or more identical, 98% or more identical, 99% or more identical, to the original sequence. For example, it is also possible to investigate the biological function of such a protein by appropriate and available in vitro assays described herein or known in the art. “Functionally active” as used herein refers to a polypeptide, i.e., a fragment or derivative, having a structural, regulatory, or biochemical function of protein, such as biological activity, according to aspects to which the polypeptide, i.e., the fragment or derivative, of the present disclosure is associated herein. Accordingly, in one embodiment, the variant of the present disclosure refers to a functional equivalent.
Thus, the specification encompasses variants having as little as 30% sequence homology to the fragments. Further, the claims require the AtaA fragments and variants thereof must retain the properties of having reduced self-aggregation while maintaining an adhesive function. The specification does not disclose any representative species of variants containing mutations, additions and deletions of the functionally defined fragments of SEQ ID NO: 1.
The instant specification discloses the difficulty of designing a recombinant AtaA protein with the Nhead domain at paragraph [0094]:
It is extremely challenging to design a construct of a recombinant protein. It is not easy, even for a protein engineering specialist, to design a trimer to properly form and correctly fold. It was inferred that the structure of Nhead is primarily comprised of a β strand from the primary structure (amino acid sequence). It was expected that formation of a trimer through association of a β strand would be difficult. It was understood that the neck, which is present on the C-terminus side of Nhead, also needed to be included in a construct.
Figure 3C depicts the amino acid sequence of the fusion protein AtaA59-325-GCN4PII-His, which comprises amino acids 1-268 of SEQ ID NO: 1, which includes the Nhead domain, the neck, the leading CC of the Nstalk domain and the sequence of GCN4PII-His. Figure 9C depicts the same AtaA fragment (Nhead, neck, leading CC of Nstalk) plus GCN4PII, a glycine linker, a SNAP protein and a His tag; Figure 12C depicts the same AtaA fragment, but with the SNAP protein and the GCN4PII reversed and Figure 14C depicts the same AtaA fragment, but missing GCN4PII. Figure 15C depicts a slightly shorter fragment of AtaA (residues 1-257 of SEQ ID NO: 1, which includes the head and neck) followed by GCN4PII, a glycine linker, SNAP protein and a His tag. Finally, Figure 27 depicts the SpyCatcher protein attached to the 1-268 AtaA fragment of SEQ ID NO: 1 followed by GCN4PII-His. In summary, the specification discloses several experimental fusion proteins comprising the same or highly homologous fragment of SEQ ID NO: 1 (residues 1-268 or 1-257).
Applicant does not teach how up to 70% of the residues in SEQ ID NO: 1, a protein containing over 3500 amino acids, can be mutated in to result in a fragment or variant capable of maintaining adhesive function while having reduced self-aggregation. The number of mutations generally possible in any given protein that can be made with a reasonable expectation of success are limited. Certain positions in the sequence are critical to the protein's structure/function relationship, e.g., such as various sites or regions directly involved in binding, activity and in providing the correct three-dimensional spatial orientation of binding and active sites. The specification explicitly states it “is extremely challenging to design a construct of a recombinant protein…even for a protein engineering specialist”.
Further, the amendment to recite of “an amino acid sequence that is different from the amino acid sequence of AtaA” in claim 37 represents a large genus of proteins. The instant specification discloses the specific example of SNAP protein (paragraph [0064]). Again, without knowing the identity of this “amino acid sequence that is different from the amino acid sequence of AtaA”, the skilled artisan does not know how to carry out the claimed methods. Due to the large quantity of experimentation necessary to design AtaA fragments and variants having an adhesive function and reduced self-aggregation and test the same for function, the lack of direction/guidance presented in the specification regarding the same, the complexity of designing recombinant AtaA fragments and variants with the required properties, the unpredictability of the effects of mutation on protein structure and function, and the breadth of the claims which fail to recite limitations on the AtaA fragments/variants and “an amino acid sequence that is different from the amino acid sequence of AtaA”, all of which makes it difficult to carry out the claimed methods, undue experimentation would be required of the skilled artisan to make and use the claimed invention.
Written Description
The rejection of claims 27, 28, 31-34, 36, 37, 51, 52, 55-58 and 60 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is maintained for reasons of record and the following. The amendment addresses the issue with regard to the functionality-imparting entities and clearly defines the second substance as comprising a support. Nevertheless, Applicant’s amendment to independent claims 27 and 37 still encompasses an amino acid sequence having only 80% identity to residues 2-257 of SEQ ID NO: 1 or a variant sequence thereof wherein the polypeptide does not have a self-aggregation property and has an adhesive property. Further, since claims 27 and 37 recite “a polypeptide which comprises a fragment of the amino acid sequence set forth in SEQ ID NO: 1 or a variant sequence thereof, wherein the polypeptide comprises an amino acid sequence having at least 80% identity to an amino acid sequence of amino acid positions 2-257 of SEQ ID NO: 1”, the fragment and variant of the polypeptide need not comprise residues 2-257 of SEQ ID NO: 1. In other words, Applicant’s amendment defines the polypeptide, not the fragment or variant to which the claim is drawn. Further, the recitation of “an amino acid sequence that is different from the amino acid sequence of AtaA” in claim 37 still represents a large genus of proteins.
Response to Arguments
Applicant argues at p. 10, 2nd paragraph of the Remarks filed 01/23/2026 that the claims have been amended to encompass to the Nhead-containing region (residues 2-257), exclude the Chead region and impose an 80% identity limitation, “which results in a claim scope that reflects the constructs the examiner acknowledged as described”.
This argument has been fully considered, but is not found persuasive. To clarify, the examiner did not argue that an 80% identity limitation reflects the constructs the examiner acknowledged were described. As noted above, since claims 27 and 37 recite “a polypeptide which comprises a fragment of the amino acid sequence set forth in SEQ ID NO: 1 or a variant sequence thereof, wherein the polypeptide comprises an amino acid sequence having at least 80% identity to an amino acid sequence of amino acid positions 2-257 of SEQ ID NO: 1”, the fragment and variant of the polypeptide need not comprise residues 2-257 of SEQ ID NO: 1. In other words, Applicant’s amendment defines the polypeptide, not the fragment or variant to which the claim is drawn.
Applicant’s amendment still encompasses a method that utilizes fragments and variants that require adhesion or immobilization of a first and second substance. Applicant defines fragments at paragraph [0042]:
As used herein, “fragment” refers to a polypeptide or polynucleotide with a sequence length of 1 to n-1 with respect to a full-length polypeptide or polynucleotide (with the length of n). The length of the fragment can be varied as appropriate according to the objective thereof, and the lower limit of the length thereof, in the case of polypeptides, includes, for example, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50 and more amino acids; and lengths represented by integers not specifically listed here (e.g., 11) can also be appropriate as lower limits. A fragment of the polypeptide of the present disclosure consists of preferably 237 or more and 3364 or less amino acids and more preferably 256 or more and 2846 or less amino acids. Examples of the lower limit include, but are
not limited to, 237 amino acids, 256 amino acids, 300 amino acids, 400 amino acids, 500 amino acids, 600 amino acids, 700 amino acids, 800 amino acids, 900 amino acids, 1000 amino acids, and the like. Examples of the upper limit include but are not limited to, 1000 amino acids, 1100 amino acids, 1200 amino acids, 1300 amino acids, 1400 amino acids, 1500 amino acids, 1600 amino acids, 1700 amino acids, 1800 amino acids, 1900 amino acids, 2000 amino acids, 2100 amino acids, 2200 amino acids, 2300 amino acids, 2400 amino acids, 2500 amino acids, 2600 amino acids, 2700 amino acids, 2800 amino acids, 2846 amino acids, 2900 amino acids, 3000 amino acids, 3100 amino acids, 3200 amino acids, 3300 amino acids, and 3364 amino acids. The length can be any other length, as long as a desired property (e.g., lack of self-aggregation property or maintaining an adhesive property) is maintained.
Thus, the specification encompasses a vast genus of fragments. In addition, the recited variants are defined at paragraph [0031] of the instant specification:
The “variant”, “derivative”, “analog” or “mutant” (of adhesive polypeptides and the like) as used herein are used interchangeably, and the above terms preferably include molecules including regions that are substantially homologous to the protein (e.g., adhesive polypeptide) of interest, although not intended to be limiting; and in the case of amino acid sequence, nucleic acid sequence (nucleotide sequence, base sequence), such sequences are referred to as “altered sequence”, “derived sequence”, “analogous sequence”, and “mutated sequence”. Such molecules, in various embodiments, are at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 99% identical, throughout amino acid sequences of the same size, or in comparison with sequences to be aligned by conducting alignment with a computer homology program that is known in the art; or nucleic acids encoding such molecules can hybridize to sequences encoding component proteins under (highly) stringent, moderately stringent, or non-stringent conditions. This means that each is a product of protein alteration by amino acid substitutions, deletions and additions, in which the variant or derivative thereof still exhibits the biological function of the original protein, but not necessarily to the same degree. The variant may have a sequence that is preferably 70% or more identical, more preferably 80% or more identical, even more preferably 90% or more identical, still even more preferably 95% or more identical, 98% or more identical, 99% or more identical, to the original sequence. For example, it is also possible to investigate the biological function of such a protein by appropriate and available in vitro assays described herein or known in the art. “Functionally active” as used herein refers to a polypeptide, i.e., a fragment or derivative, having a structural, regulatory, or biochemical function of protein, such as biological activity, according to aspects to which the polypeptide, i.e., the fragment or derivative, of the present disclosure is associated herein. Accordingly, in one embodiment, the variant of the present disclosure refers to a functional equivalent.
The specification encompasses variants having as little as 30% sequence homology to the fragments. Thus, Applicant’s claims are drawn to a large genus of AtaA fragments and variants thereof that must retain the properties of having reduced self-aggregation while maintaining an adhesive function. However, the specification only discloses the Nhead domain (residues 1-268 of SEQ ID NO: 1), which must be recombinantly produced in E. coli to have reduced self-aggregation properties, as a starting point for designing Nhead domain containing recombinant proteins. Moreover, the specification does not disclose any representative species of variants containing mutations, additions and deletions of the functionally defined fragments of SEQ ID NO: 1. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics of the recited fragments, the specification does not provide adequate written description of the claimed genus. Finally, the amendment to claim 37, part (a)(ii) recites “an amino acid sequence that is different from the amino acid sequence of AtaA”, which still represents a large genus of proteins. The instant specification discloses the specific example of SNAP protein (paragraph [0064]). Again, in the absence of sufficient recitation of distinguishing identifying characteristics of the recited amino acid sequences different from AtaA, the specification does not provide adequate written description of the claimed genus.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 5712720911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675