DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. The Preliminary Amendment filed on September 3, 2024, has been received and entered.
3. Applicant’s election without traverse of Group I on November 11, 2025, is acknowledged.
Claim Disposition
4. Claims 20-75 and 77-118 have been cancelled. Claims 1-19 and 76 are pending. Claims 1 and 5-19 are under examination. Claims 2-4 and 76 are withdrawn from further consideration pursuant to 37 CFR 1.12(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Information Disclosure Statement
5. The Information Disclosure Statements filed on November 7, 2023, June 7, 2024, November 5, 2024, January 27, 2025, April 15, 2025 and November 11, 2025, have been received and entered. The references cited on the PTO-1449 Form have been considered by the examiner and a copy is attached to the instant Office action. Note that references have been lined through based on an incomplete dates.
Drawing
6. The drawings filed on August 10, 2023, have been accepted by the examiner.
Specification Objection
7. The specification is objected to for the following informalities:
The specification is objected to because Table 5 (page 138); and Table 6 on page 142 (also see pages 28-30) has a sequences without a sequence notation.
The specification is objected to because organism names are not italicized, see ‘Bacillus subtilis’ on page 145, among others throughout.
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The following is suggested: "Method for stabilizing a polypeptide and fusion proteins".
Appropriate correction is required.
Claim objection
8. Claims 1 and 5-19 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that 1 recite the specific polypeptide deemed as first and second in the fusion and the conditions that the fusion is exposed to and the activity that is retained. The dependent claims hereto are also included.
For clarity it is suggested that claim 5 is amended to read, “The method of claim 1, further comprising removing the fusion protein….”.
For clarity and precision of claim language it is suggested that claim 18 is amended to read, “wherein the one or more conditions is heat shock….”.
Appropriate correction is required.
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.
9. Claims 1 and 5-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), 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.
The claimed invention is directed to “a method for stabilizing a first polypeptide comprising expressing a fusion that comprises the first polypeptide and a second polypeptide having phase behavior, however, the fusion is not defined as the first and second polypeptide are not described and the conditions that the fusion is exposed to is not defined and the activity that is asserted as substantially retained is not defined (see claim 1 in its entirety). Thus the claimed invention is not adequately described for an ordinary skilled worker to ascertain what polypeptide in the vast amounts that exist could be the first or the second and the criteria of phase behavior does not limit to the just the second polypeptide nor limit necessarily the types of polypeptides. The claimed embodiments encompasses a large variable genus of polypeptides that can be construed as first and second and conditions that could destabilize the first and second polypeptide. In addition, there are no indicia in the claims about a quantifiable amount for the recited “substantial activity”. The claimed invention is not adequately described because the specification at page 2 discloses that the second polypeptide with phase behavior can be an enzyme or a derivative or catalytic fragment thereof, an antibody or derivative/fragment, a signaling molecule or fragment/derivative, a structural protein or fragment/derivative, or a hormone/fragment/derivative. Note also that although not asserted the first polypeptide encompasses a polypeptide with phase behavior. The claims are clearly not commensurate in scope with the disclosure in the specification.
The art generally recognizes that polypeptides with phase behavior, most notably elastin-like polypeptides (ELPs), undergo stimuli-responsive phase separation in aqueous solutions, commonly exhibiting Lower Critical Solution Temperature (LCST) behavior, where they transition from soluble to insoluble upon heating. These materials, composed of VPGXG pentapeptide repeats, form a polymer-rich phase (coacervation) above a, tunable temperature, making them essential for drug delivery, tissue engineering, and protein purification. The specification discloses that phase behavior refers to any polypeptide capable of undergoing phase transition due to the application of an environmental factor thus the first and second polypeptide claimed are capable of undergoing a phase transition or phase behavior, and note claim 1 recites exposure to one or more conditions.
The specification also discloses that the first polypeptide is an enzyme and the activity is kcat [0022] and retains activity at 4 degrees Celcius for about 1 week and can retain from 65% to 100% of activity after exposure to a condition. Note that the claims are not limited to said disclosure. The claimed invention is overly broad and not commensurate in scope with the disclosure and no correlation is made between structure and function. The specification fails to provide a representative number of species for the claimed genus to show that 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.
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
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.
10. Claims 1 and 5-19 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.
Claims 1 and the dependent claims hereto are rejected as being indefinite because the claim does not set forth what conditions the polypeptide is exposed it could be temperature, acid, radiation, or simply a pH change and there’s no indication that the second polypeptide that is fused to first polypeptide is safe guarded from the undefined conditions. In addition, there are no quantifiable measurements for ‘substantial activity retained’ and said activity is not defined thus it is not clear if the activity remaining is the desired activity. The dependent claims hereto are also included.
Claim 5 lacks clear antecedent basis for the recitation of ‘retains its activity’ when the independent claim recites “substantially retains its activity”.
Claim 6 lacks clear antecedent basis for the recitation of “the one or more conditions that unfold, degrade, misfold or destabilize the first polypeptide” because claim 1 recites “conditions that would destabilize”. See also claims 7-17 with similar language or that depend from claim 6.
Claim 19 is indefinite for the recitation of exposure time periods when there is no indication in the claim of what specific condition or polypeptide being exposed to be able to garner retention of activity. The length of exposure would correlate with the type of protein and condition and both are unknown, thus the claim language lacks clarity.
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.
11. Claim(s) 1 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by ISOLERE BIO., INC.( WO 2020/037100A1, 2020, of record in the application).
The primary reference teaches a fusion protein comprising a polypeptide having phase behavior (expressing a capture fusion protein comprising a polypeptide with phase behavior fused to an affinity capture molecule, (see paragraphs [0005] and [0016]). Therefore, the limitations of the claims are met by the reference.
12. Claim(s) 1 and 5 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Chilkoti ( US Patent No. 6,852,834, of record in the application).
The primary reference teaches a method for stabilizing a first polypeptide, the method comprising expressing a fusion protein (first polypeptide) that were stable at greater than 55°C and salt concentrations of 1, 2, and 3 M (see column 27, line 10 to 25; and claim 1 of Chilkoti). Claim one of the reference teaches the first polypeptide and a second polypeptide, wherein the second polypeptide is a polypeptide having phase behavior (fusion protein comprising a first and second polypeptide with one of the polypeptides comprising one or more phase transition proteins (see claim 1 of the reference); wherein when the fusion protein is exposed to one or more conditions that would be stable the first polypeptide, the first polypeptide substantially retains its activity (the biological active polypeptide (first polypeptide) in the fusion protein remain stable (retains its activity)) after repeated challenges in one or more conditions that would be stable the first polypeptide such as temperature above 55°C and salt concentrations of 1, 2,and 3 M; (see column 11, line 65 to 67; column 12, lines 1 to 4; and column 27, lines 10 to 25). Regarding claim five the reference discloses comprising removing the fusion protein from the conditions and cleaving the first polypeptide from the second polypeptide, wherein the first polypeptide retains is activity compared to a control first polypeptide that has not been exposed to the conditions(fusion protein that may be isolated with phase transition(removing the fusion protein from the conditions) comprising a proteolytic cleavage site (for cleaving the first from the second polypeptide) wherein the target protein retains is activity after the cleavage tag is removed (see col. 11, lines 56-67, col. 12, lines 1-4 and claim 17 of Chilkoti). Therefore, the limitations of the claims are met by the reference.
Conclusion
13. No claims are presently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652