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 .
Election/Restrictions
Applicant’s election without traverse of claims 1-3, 5, 12, 14-15, 19, 22, and 25; as well as the species elections of SEQ ID NO: 1, option (iii) in claim 5, option (v) in claim 12, option (iv) in claim 15, and option (i) in claim 22; in the reply filed on 10/27/2025 is acknowledged.
Claims 24, 29-33, 37-38, and 40-41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/27/2025.
In view of the prior art search, the species election is expanded to include option (iii) in claim 12.
Priority
This application is a 371 of PCT/GB2021/053304 (12/15/2021) which claims priority to GB2019817.2 (12/15/2020).
Information Disclosure Statement
The information disclosure statements (IDS) filed on 6/14/2023, 9/7/2023, and 12/16/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings are objected to for the following reasons:
37 CFR 1.84(u)(1) states “View numbers must be preceded by the abbreviation “FIG.”.
In the current case, the view numbers for Figures 1-11 are preceded by the word “Figure” instead of the abbreviation “FIG.”. View numbers should be updated to recite the abbreviation “FIG.”. Any changes to the drawings should also be reflected in the specification.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
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.
Claims 1-3, 5, 12, 14-15, 19, 22, and 25 are rejected 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. 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.
Regarding written description, 35 U.S.C. 112(a) and the first paragraph of pre-AlA 35 U.S.C. 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010). To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention (MPEP § 2163(I)).
MPEP 2163(II)(A)(3)(a)(i and ii) states that 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., .759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, claim 1 is directed to a mutant Kunitz-type soybean trypsin inhibitor (SBTI) family polypeptide comprising two or more amino acid mutations compared to the corresponding unmutated SBTI family polypeptide, with one or more mutations in positions 22-25 of SEQ ID NO: 1 and one or more mutations in positions 47-50 of SEQ ID NO: 1. Mutations to the amino acid sequence include any substitution, insertion, or deletion. This encompasses an infinite number of potential sequences. Any of these residues may be substituted with any amino acid, any of the residues may be deleted, and any number of amino acid residues may be inserted in the claimed regions. There is not a disclosed structure-function relationship to make clear which of these infinite mutant polypeptides would have the claimed function, i.e. binding selectively to a ligand and resistance to cleavage by pepsin.
Additionally, claim 14 recites that the mutant SBTI polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NO: 1. SEQ ID NO: 1 has 181 residues. This means that up to 54 residues may differ from the wildtype sequence. There is not sufficient structure-function information to indicate which residues are critical for enzyme function, i.e. which residues can or cannot be mutated while maintaining the claimed function.
There is written description support for specific amino acid mutations in the claimed regions that result in the claimed function (see instant specification pp. 40-42, for example). However, these examples are not representative of the entire genus of claimed polypeptides, which encompasses infinite possibilities for mutation, especially given the multiple roles of SBTI family proteins and the unpredictability of modifications on function (see instant specification p. 3). Thus, it is not clear that the applicant was in possession of the full scope of the invention at the time of filing.
Claims 2-3, 5, 12, 15, 19, 22, and 25 are included in this rejection because they depend on claim 1 and do not clarify the issue.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5, 12, 14-15, 19, 22, and 25 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 applications subject to pre-AIA 35 U.S.C. 112, the 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) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 2 recites the broad recitation “serine protease inhibitor”, and the claim also recites “preferably a trypsin and/or chymotrypsin inhibitor” which is the narrower statement of the range/limitation.
Claim 19 recites the broad recitation “inflammatory disease or condition”, and the claim also recites “such as an inflammatory bowel disease” which is the narrower statement of the range/limitation. Claim 19 also recites “neoplastic disease or condition”, and the claim also recites “such as a GI tract cancer” which is the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claims 1 and 15 recite “unmutated (e.g. wild-type)”. Claim 3 recites “(e.g. SBTI, Uniprot ID P01070)”. Claim 14 recites “(e.g. 75%, 80%, 85% or 90%)”. Claim 19 recites “(such as inflammatory bowel disease”) and “(such as a GI tract cancer)”. Claim 25 recites “(optionally formulated for oral administration)”. The parentheses, as well as the use of “e.g.”, make it unclear whether these are intended to be required or optional claim elements. It is suggested that the claims be amended to remove the parentheses and “e.g.” to clarify the limitations required by each of these claims.
Claims 5, 12, and 22 are included in this rejection because they depend on a rejected claim and do not clarify the issue.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 12, 14-15, and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pasquali et al., BR102018008975A2 (published 11/19/2019).
Regarding claim 1, Pasquali teaches mutating a Glycine max (soybean) Kunitz trypsin inhibitor (KTI3) by replacing Ile or Leu codons with Met (Pasquali para. 42). The amino acid sequence of the mutated polypeptide comprises a mutation at position 23 and a mutation at position 50 relative to instant SEQ ID NO: 1 (see sequence alignment in OA Appendix). Thus, Pasquali teaches a mutant Kunitz-type SBTI comprising two or more amino acid mutations relative to wildtype, including a mutation in a first domain corresponding to positions 22-25 of instant SEQ ID NO: 1 and a mutation in a second domain corresponding to positions 47-50 of instant SEQ ID NO: 1.
Regarding the limitations “wherein the mutant SBTI family polypeptide (a) binds selectively to a ligand that does not bind to the corresponding unmutated (e.g. wild-type) SBTI family polypeptide; and (b) is resistant to cleavage by pepsin”, these are functional limitations of the claimed mutant SBTI polypeptide. Any polypeptide having this same structure (i.e., a mutation in positions 22-25 and in positions 47-50) must necessarily have the same function, absent any unclaimed features necessary for such a function. Therefore, the polypeptide taught by Pasquali, which has the same structure as the claimed polypeptide, anticipates claim 1.
Regarding claim 2, Pasquali teaches that the unmutated polypeptide is a trypsin inhibitor (Pasquali para. 42).
Regarding claim 3, Pasquali teaches that the sequence of KTI3 is mutated by replacing Ile or Leu codons with Met (Pasquali para. 42). The wildtype sequence of KTI3, with no mutations to Met, is 100% identical to instant SEQ ID NO: 1 (see sequence alignment in OA Appendix). Thus, Pasquali teaches that the unmutated SBTI polypeptide has an amino acid sequence as set forth in SEQ ID NO: 1.
Regarding claim 12, Pasquali teaches that the SBTI polypeptide further comprises a mutation in a domain corresponding to positions 63-65, specifically position 64 (see sequence alignment in OA Appendix).
Regarding claim 14, Pasquali teaches that the mutant SBTI polypeptide is 84% identical to instant SEQ ID NO: 1 (see sequence alignment in OA Appendix).
Regarding claims 15 and 19, “the ligand that does not bind to the corresponding unmutated (e.g. wild-type) SBTI family polypeptide” refers to a functional limitation of the claimed polypeptide, as discussed above. Any polypeptide having this same structure (i.e., a mutation in positions 22-25 and in positions 47-50) must necessarily have the same function, absent any unclaimed features necessary for such a function. Therefore, the polypeptide taught by Pasquali, which has the same structure as the claimed polypeptide, anticipates claims 15 and 19.
Claims 1 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Oman et al., US20190128896A1.
Regarding claim 1, Oman teaches protein sequences for Kunitz trypsin inhibitors from soybean (Oman Abstract; p. 24 Ex. 4). Oman teaches a Kunitz trypsin inhibitor amino acid sequence according to SEQ ID NO: 23, which has substitutions at all of positions 22-25 and at position 47 relative to instant SEQ ID NO: 1 (see sequence alignment in OA appendix; Oman p. 24 para. 112). Thus, Oman teaches a Kunitz-type SBTI comprising two or more amino acid mutations relative to wildtype, including at least one mutation in a first domain corresponding to positions 22-25 of instant SEQ ID NO: 1 and at least one mutation in a second domain corresponding to positions 47-50 of instant SEQ ID NO: 1.
Regarding the limitations “wherein the mutant SBTI family polypeptide (a) binds selectively to a ligand that does not bind to the corresponding unmutated (e.g. wild-type) SBTI family polypeptide; and (b) is resistant to cleavage by pepsin”, these are functional limitations of the claimed mutant SBTI polypeptide. Any polypeptide having this same structure (i.e., mutations in positions 22-25 and in positions 47-50) must necessarily have the same function, absent any unclaimed features necessary for such a function. Therefore, the polypeptide taught by Oman, which has the same structure as the claimed polypeptide, anticipates claim 1.
Regarding claim 5, Oman teaches a Kunitz-type SBTI amino acid sequence according to SEQ ID NO: 23, which comprises two or more amino acid substitutions in the first domain, specifically at all of positions 22-25 (see sequence alignment in OA appendix). Option (iii) of claim 5 recites “the first domain comprises two or more amino acid substitutions and/or insertions and/or the second domain comprises two or more amino acid substitutions and/or insertions”. Given the use of and/or, it is considered that only one of either the first or second domain is required to have two or more amino acid substitutions. Thus, the polypeptide sequence taught by Oman, which has two amino acid substitutions relative to instant SEQ ID NO: 1 in the first domain, anticipates claim 5.
Claim Rejections - 35 USC § 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 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.
Claims 22 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Pasquali et al. as applied to claims in view of Takakura et al., Journal of pharmaceutical sciences; 78(3):219-22.
Pasquali teaches the mutant SBTI family polypeptide of claim 1, as discussed above. Pasquali does not teach that the polypeptide is conjugated to another molecule (claim 22) or a composition comprising the polypeptide as recited in claim 25.
Regarding claim 22, Takakura teaches a Kunitz-type soybean trypsin inhibitor (STI) polypeptide conjugated to another molecule, dextran (Takakura Abstract). Takakura teaches that conjugation of peptides to biocompatible macromolecules including dextran is of interest for controlling pharmaceutical properties of peptides (Takakura p. 219 para. 1). Takakura teaches that dextran is a desirable material for chemical modification of proteins (Takakura p. 219 para. 1). Takakura teaches that dextran conjugation of STI resulted in the reduction of urinary excretion and a prolonged persistence in plasma in mice (Takakura p. 221 para. 1). Takakura teaches that immunogenicity is one of the most important problems for protein drugs and this might be overcome by dextran conjugation and that dextran conjugation is useful for the control of the biopharmaceutical and pharmacological properties of protein drugs (Takakura p. 221 para. 8-9).
Regarding claim 25, Takakura teaches that the SBTI family polypeptide, or STI, is included in a pharmaceutical composition that is administered to mice (Takakura p. 219 “Experimental Section”).
It would have been obvious for a skilled artisan to combine the teachings of Pasquali and Takakura and conjugate the SBTI family polypeptide of Pasquali to another molecule. As taught by Takakura, conjugation of molecules such as dextran to soybean trypsin inhibitor proteins is an established technique in the art. Based on the teachings of Takakura it would have been obvious to a skilled artisan that the polypeptide of Pasquali could be conjugated to another molecule, and used in a pharmaceutical composition.
A person of ordinary skill in the art would have been motivated to conjugate the polypeptide of Pasquali to another molecule such as dextran because the conjugation of peptides to biocompatible macromolecules is beneficial for controlling the pharmaceutical properties of polypeptides, including soybean trypsin inhibitors. Takakura teaches that conjugation of dextran to STI resulted in improved pharmaceutical properties when given to mice, and thus a skilled artisan would have been motivated to create a conjugated SBTI polypeptide to achieve improved properties. An ordinary artisan would have similarly been motivated to use the polypeptide of Pasquali in a composition, such as a pharmaceutical composition, as Takakura has shown that similar STI polypeptide conjugates are useful as biopharmaceuticals.
A skilled artisan would have had a reasonable expectation of success in creating a polypeptide according to Pasquali conjugated to a molecule such as dextran because this is an established and beneficial technique for soybean trypsin inhibitor polypeptides similar to the polypeptide taught by Pasquali, and thus an ordinary artisan could reasonably expect success in obtaining a conjugate and composition comprising the SBTI of Pasquali.
Conclusion
Claims 1-3, 5, 12, 14-15, 19, 22, and 25 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY F EIX/Examiner, Art Unit 1653
/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
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