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 .
Claims 33-52 are still at issue and are present for examination.
Election/Restrictions
Applicant's election with traverse of the invention of Group I, claims 33-46, drawn to a engineered reverse transcriptase reaction, in the paper of 3/13/2026, is acknowledged. Applicants traverse the restriction requirement on the grounds that the search and examination of the two different groups does not present an undue burden to the Office.
Applicants traversal is acknowledged and has been considered, however, is found non-persuasive for the reasons previously made of record. As stated in the restriction requirement of 12/29/2026, the inventions of Group I and Group II are related as product and process of use. Invention I and invention II are related as product and processes of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product (MPEP § 806.05(h)). In the instant case, the genetically engineered fusion reverse transcriptase can be used in a materially different process such as one in which the genetically engineered fusion reverse transcriptase is used to make an antibody. Further while a search of the different groups may overlap, it is not coextensive and thus there would be an additional burden on the office should the restriction requirement not be made.
The requirement is still deemed proper and is therefore made FINAL.
Applicant's election with traverse of the invention of the following species:
Species Group 1: “D449G”.
Species Group 2: 1) P448A and D449G
Species Group 3: SEQ ID NO: 22.
in the paper of 3/13/2026, is acknowledged
Claims 39-46, 47-52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
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."
Applicants filing of information disclosure statements on 12/13/2023, 4/3/2024, 7/24/2024 and 11/13/2024 are acknowledged and have been considered.
Specification
The disclosure is objected to because of the following informalities:
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth: The following portions of the specification list sequences which appear to meet the definition for an nucleic acid sequence, but do not have an associated SEQ ID No: Figure 17.
Further applicants are advised that when an amino acid sequence or nucleic acid sequence appear in a figure that an associated sequence identifier must also appear in the figure itself or in the description of the figure.
Appropriate correction is required.
Claim Objections
Claim 33 is objected to because of the following informalities:
Claim 33 recites “a_M66L”. It is suggested this be “a M66L”.
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) 33-35 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) 33-35 are directed to all possible engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptases comprising relative to SEQ ID NO: 15: (a) a M66L mutation and an L435G mutation; and (b) one or more additional mutations selected from the group consisting of M39V, H503V, H634Y, P448A, and D449G. The specification, however, only provides the representative species of that engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptase comprising relative to SEQ ID NO: 15: (a) a M66L mutation and an L435G mutation; and (b) one or more additional mutations selected from the group consisting of M39V, H503V, H634Y, P448A, and D449G wherein said MMLV reverse transcriptase comprises the amino acid sequence of SEQ ID NO:22, 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 engineered Moloney Murine Leukemia Virus reverse transcriptases 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(s) 33-35 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for that engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptase comprising relative to SEQ ID NO: 15: (a) a M66L mutation and an L435G mutation; and (b) one or more additional mutations selected from the group consisting of M39V, H503V, H634Y, P448A, and D449G wherein said MMLV reverse transcriptase comprises the amino acid sequence of SEQ ID NO:22, does not reasonably provide enablement for all possible engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptases comprising relative to SEQ ID NO: 15: (a) a M66L mutation and an L435G mutation; and (b) one or more additional mutations selected from the group consisting of M39V, H503V, H634Y, P448A, and D449G. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
Claim(s) 33-35 are so broad as to encompass all possible engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptases comprising relative to SEQ ID NO: 15: (a) a M66L mutation and an L435G mutation; and (b) one or more additional mutations selected from the group consisting of M39V, H503V, H634Y, P448A, and D449G. The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of engineered MMLV reverse transcriptase and variants encompassed by the claims. The claims rejected under this section of U.S.C. 112, first paragraph, place minimal structural limits on the engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptases encompassed by the claims. Since the amino acid sequence of a protein determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence, if any, are tolerant of modification and which are conserved (i.e. expectedly intolerant to modification), and detailed knowledge of the ways in which the proteins' structure relates to its function. However, in this case the disclosure is limited to that engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptase comprising relative to SEQ ID NO: 15: (a) a M66L mutation and an L435G mutation; and (b) one or more additional mutations selected from the group consisting of M39V, H503V, H634Y, P448A, and D449G wherein said MMLV reverse transcriptase comprises the amino acid sequence of SEQ ID NO:22.
While recombinant and mutagenesis techniques are known, it is not routine in the art to screen for multiple substitutions or multiple modifications, as encompassed by the instant claims, and the positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
The specification does not support the broad scope of the claims which encompass any possible engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptases comprising relative to SEQ ID NO: 15: (a) a M66L mutation and an L435G mutation; and (b) one or more additional mutations selected from the group consisting of M39V, H503V, H634Y, P448A, and D449G, because the specification does not establish: (A) regions of the engineered MMLV reverse transcriptase which may be modified effecting the reverse transcriptase activity; (B) the general tolerance of engineered MMLV reverse transcriptases to modification and extent of such tolerance; (C) a rational and predictable scheme for modifying any amino acid residue of an engineered MMLV reverse transcriptase with an expectation of obtaining the desired biological function; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful. Because of this lack of guidance, the extended experimentation that would be required to determine which substitutions would be acceptable to retain the required lipase activities and the fact that the relationship between the sequence of a peptide and its tertiary structure (i.e. its activity) are not well understood and are not predictable (e.g., see Ngo et al. in The Protein Folding Problem and Tertiary Structure Prediction, 1994, Merz et al. (ed.), Birkhauser, Boston, MA, pp. 433 and 492-495; Franceus et al., J. Ind. Microbiol. Biotechnol. Vol 44, pp 687-695, 2017), it would require undue experimentation for one skilled in the art to arrive at the majority of those MMLV reverse transcriptases of the claimed genus.
Thus, applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including any engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptases comprising relative to SEQ ID NO: 15: (a) a M66L mutation and an L435G mutation; and (b) one or more additional mutations selected from the group consisting of M39V, H503V, H634Y, P448A, and D449G. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of those engineered MMLV reverse transcriptases having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 33-38 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Clark et al. (WO 2021/119320).
Clark et al. (WO 2021/119320) disclose a number of engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptase comprising a M66L mutation, an L/K435G mutation; a D448A mutation and a D449G mutation relative to the wild type of SEQ ID NO:15 (see paragraph [00017], page 7, claim 1 and supporting text). Clark et al. further teach the above MMLV mutations in the background of SEQ ID NO:1 which has greater than 99% sequence identity to instant SEQ ID NO:22 and comprises an amino acid sequence as set forth in SEQ ID NO:22.
Thus claim(s) 33-38 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Clark et al. (WO 2021/119320).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 33-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-26 of copending Application No. 18/744,254 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 12-26 of copending Application No. 18/744,254 (reference application) drawn to an engineered fusion reverse transcriptase comprising:(a) at least one DNA binding domain selected from a DNA binding domain from an archaeal DNA binding protein, wherein the archaeal DNA binding protein is selected from the group consisting of Sto7d, Sso7d, Sis7b, Sis7a, Ssh7b, Sto7, Aho7C, Aho7B, Aho7A, Mcu7, Mse7, Sac7e, and Sac7d and (b) an engineered reverse transcriptase, wherein the engineered reverse transcriptase comprises the combination of the following amino acid substitutions in SEQ ID NO: 7: (i) E69K, L139P, E302R, T306K, W313F, T330P, and N454K; and one or more of M39V, P47L, M66L, F155Y, D200N, D200E, H204R, G429S, L435G, L435K,P448A, D449G, H503V, D524N, T542D, E545G, D583N, H594Q, L603W, L603F,E607K, E607G, P627S, H634Y, H638G, A644V, D653H, K658R and L671P; or (ii) E69K, L139P, D200N, E302R, T306K, W313F, T330P, L435G, P448A,D449G, N454K, D524N, L603W, and E607K and one or more of M39V, P47L, M66L,F155Y, H204R, G429S, H503V, T542D, E545G, D583N, H594Q, P627S, H634Y,H638G, A644V, D653H, K658R and L671P, anticipate/make obvious instant claims 33-38 drawn to a engineered Moloney Murine Leukemia Virus (MMLV) reverse transcriptases comprising relative to SEQ ID NO: 15: (a) a M66L mutation and an L435G mutation; and (b) one or more additional mutations selected from the group consisting of M39V, H503V, H634Y, P448A, and D449G.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 6-3 EST Mon-Fri.
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rgh
4/17/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
Prosecution Insights