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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/15/2025 has been entered.
Applicant’s cancellation of claims 23, 27, 29, amendment of claims 11, 16, in the paper of 9/15/2025, is acknowledged. Applicants' arguments filed on 9/15/2025, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Claims 11, 12, 14-22, 25, 26. 28 are still at issue and are present for examination.
Amendments of Claims
Applicants attention is directed to the proper method of amending the claims as per MPEP 714, 37 CFR 1.121 Manner of making amendments in application. Applicants attention is directed to the currently amended claim 11 as and example (also claims 12, 14, 15, 16, 20) which appears to be amended from that of previous claim 11, as it existed in the paper of 4/7/2025. It appears that applicants have included amendments to the claims submitted on 9/2/2025 that were not entered, as indicated in the advisory of 9/11/2025. Applicants filing of the RCE on 9/15/2025 does not indicate that the previous un-entered amendment be entered, only that the “enclosed” amendment be entered. Applicants “enclosed” amendment includes amendments made and not entered in the amendment of 9/2/2025. Further these amendment are not properly made with underlining and/or strike through. The failure to follow proper amendment procedures may introduce confusion into the record and prosecution. Applicants are requested to follow proper amendment procedure in the future to avoid confusion and lack of clarity in prosecution.
Election/Restrictions
Applicant's election with traverse of the invention of Group 1, claims 11-28, to a room temperature amplification reaction system comprising a cold-active bacteriophage uvsX protein, in the paper of 11/12/2024, is acknowledged. Applicant's election with traverse of the following species:
Species Group 1: the uvsX protein of SEQ ID No. 3 ;
Species Group 2: the uvsY protein of SEQ ID No. 27;
Species Group 3: the gp32 protein of SEQ ID Nos. 24;
Species Group 4: E. coli polymerase klenow fragment (exo-)
Species Group 5: polyethylene glycol;
Species Group 6: PEG3000;
Species Group 7: SEQ ID Nos. 3;
in the paper of 11/12/2024, is acknowledged.
Claim 12 and 28 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
It is noted that while the subject matter of claims 14 and 15 are drawn to non-elected subject matter, these claims are included in the rejections below because claim 11 from which they depend is formatted such that claims 14 and 15 continue to read on the elected UvsX protein.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper."
Currently there are no information disclosure statements in the application file.
Claim Rejections - 35 USC § 112
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 11, 14, 15, 16-22, 25, 26 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.
Claim 11 (claims 14, 15, 16-23, 25, 26 dependent on) is indefinite in that it is unclear and confusing as to exactly what the requirements of the claimed room temperature system are with regard to the recitation “and/or a variant protein having the same function with the cold-active bacteriophage uvsY protein or the cold-active bacteriophage gp32 protein respectively”. While the claimed room temperature nucleic acid amplification reaction system is interpreted as a composition which must comprise each of the specified components (uvsX, uvsY or gp32) the use of “and/or” with regard to the variant protein having the same function is confusing and unclear. In the interest of advancing prosecution this recitation is interpreted as “or a variant protein having the same function with the cold-active bacteriophage uvsY protein or the cold-active bacteriophage gp32 protein respectively”.
Claim 11 (claims 14, 15, 16-23, 25, 26 dependent on) is further indefinite in the newly added recitation (see above comments regarding applicants amendment) “wherein the system further comprises a creatine kinase, wherein the creatine kinase is a variant on which G in position 268 is mutated into N, and wherein the creatine kinase is an amino acid sequence of SEQ ID NO: 37. The basis of the indefiniteness is that reference to a position of a mutation (i.e. 268) is unclear absent a reference amino acid sequence. While it is recognized that applicants amended claims states the creatine kinase is an amino acid sequence of SEQ ID NO:37, position 268 of SEQ ID NO:37 is not a “G” (glycine) residue.
Claim 21 is indefinite in the reference that “Tris” is a “salt ion” as “Tris” is an organic compound with the formula “(HOCH2)3CNH2”. Tris is not a salt ion.
Claim 25 is indefinite in the recitation “wherein a reaction time is 20-40 min” in that it is unclear how it further limits claim 11 drawn to a room temperature nucleic acid amplification reaction system which is interpreted as a composition.
Appropriate correction and/or comment 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.
Claim(s) 11, 14, 15, 16-23, 25, 26 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim(s) 11, 14, 15, 16-23, 25, 26 are directed to all possible room temperature nucleic acid amplification reaction systems, wherein the system comprises: a cold-active bacteriophage uvsX mutated protein having an amino acid sequence of SEQ ID NO: 3, a uvsY protein or a gp32 protein; and/or a variant protein having the same function with the cold-active bacteriophage uvsY protein or the cold-active bacteriophage gp32 protein respectively, wherein the room temperature nucleic acid amplification reaction system further comprises a fluorescent probe sequence, wherein the room temperature nucleic acid amplification is Recombinase Polymerase Amplification (RPA) and has a reaction temperature of 35-40oC, wherein the system further comprises a creatine kinase, wherein the creatine kinase is a variant on which G in position 268 is mutated into N, and wherein the creatine kinase is an amino acid sequence of SEQ ID NO: 37 (see also above rejection under 35 U.S.C. 112(b)). The specification, however, only provides the representative species of that room temperature nucleic acid amplification reaction system, wherein the system comprises: a cold-active bacteriophage uvsX protein having the amino acid sequence of SEQ ID NO: 3, wherein the room temperature nucleic acid amplification reaction system further comprises a fluorescent probe sequence, wherein the system further comprises a creatine kinase, having the amino acid sequence of SEQ ID NO: 37, encompassed by these claims. There is no disclosure of any particular structure to function/activity relationship in the disclosed species. The specification also fails to describe additional representative species of these uvsX and creatine kinase enzymes by any identifying structural characteristics or properties, for which no predictability of structure is apparent.
Regarding the level of skill and knowledge in the art of amino acid mutation, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top). Also, the unpredictability associated with amino acid mutations is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a mutation of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
Given this lack of additional representative species as encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Claim Rejections - 35 USC § 102
The rejection of claim(s) 11, 14, 15, 16-23, 25-28, 29 under 35 U.S.C. 102(a)(1) as being anticipated by Piepenburg et al. (US 8,071,308) is withdrawn based upon applicants amendment of the claims in the paper of 17/601,381.
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached on 6-3 EST Mon-Fri.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached on (571) 272-0956. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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rgh
10/6/2025
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652aa