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 1-5, 9-12, 15-17, 19, 21, 27-32 are still at issue and are present for examination.
Election/Restrictions
Applicant's election with traverse of the invention of Group II, claims 28-32, drawn to a method of performing a reverse transcriptase reaction, in the paper of 1/29/2026, 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: “altered template switching efficiency”.
Species Group 2: “Sto7”.
Species Group 3: “a K13L mutation”.
Species Group 4: “SEQ ID NO: 12”.
Species Group 5: “SEQ ID NO: 12”.
Species Group 6: “SEQ ID NO: 3”.
Species Group 7: “ M66L mutation”.
Species Group 8: Each of the mutations (an M39 mutation, an M66 mutation, a D653 mutation, an L671 mutation; or an M39V mutation and an M66L mutation) listed in claim 12 is a distinct species.
Species Group 9: “structural options (a)”.
Species Group 10: “mutation set (b)”.
Species Group 11: “SEQ ID NO: 3”.
Species Group 12: “mutation set (b(ii)”,
in the paper of 1/29/2026, is acknowledged
Claims 1-5, 9-12, 15-17, 19, 21, 27 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 10/27/2023, 2/13/2024, 7/24/2024 and 11/13/2024 are acknowledged and have been considered.
Claim Objections
Claim 28 are objected to because of the following informalities:
Claim 28 recites “from claim”, while claims 29-31 recite “of claim”. It is suggested that applicants maintain consistency throughout the claims.
Appropriate correction and/or comment is required.
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.
Claim 30 is 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 30 is indefinite in the recitation “the engineered fusion reverse transcriptase comprises a DNA binding domain comprising a mutation selected from the group consisting of a K13 mutation, a K13L mutation, a D36 mutation, and a D36L in SEQ ID NO: 2,SEQ ID NO: 12, or SEQ ID NO: 13” in that it is drawn to the method of claim 28, which lists mutation positions relative to SEQ ID NO:7. The referencing to different mutation positions in the same polypeptide using two different index sequences is indefinite in that it is unclear and confusing. The reference to a mutation position in SEQ ID NO:12 is indefinite because it is indefinite as to where the corresponding position occurs in SEQ ID NO:7 as an alignment of SEQ ID NO:2 and SEQ ID NO:7 does not fully align (see alignment below).
SEQ 7: 252 YRASAKKAQICQ-KQVKYLGYLLKEGQRWLTEARKETVMGQPTPK-TPRQLREFLGTAG 308
|: |: | : |:| :| :: : : :| | : | |::| : | :|
SEQ 12: 8 YKGEEKEVDISKIKKVWRVGKMIS----FTYDDNGKTGRGAVSEKDAPKELLQMLEKSG 62
It is suggested that when referencing mutation positions in the same polypeptide, applicants use a single reference amino acid sequence.
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) 32 is 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) 32 is directed to all possible methods for performing a reverse transcription reaction for generating a nucleic acid product from an RNA template using an engineered fusion reverse transcriptase, wherein the engineered fusion reverse transcriptase comprises: (a) at least one archaeal DNA binding domain; and
(b) an engineered reverse transcriptase, wherein the amino acid sequence of T330P mutation, an R411F mutation, a P448A mutation, a D449G mutation, an H503V mutation, an H594K mutation, L603W mutation, an E607K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (ii) an L139P mutation, a D200N mutation, a T330P mutation, an L603W mutation, and an E607K mutation, and further comprising at least one mutation selected from the group consisting of: an M39V mutation, an M66L mutation, an E69K mutation, an F155Y mutation, an E2010 mutation, a T287A mutation, an E302R mutation, a T306K mutation, a W313F mutation, an R411F mutation, an L435G mutation, a P448A mutation, a D449G mutation, an N454K mutation, an H503V mutation, an H594K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (iii) an A32V mutation, an L72R mutation, a D200C mutation, a G248C mutation, an E286R mutation, an E302R mutation, a W388R mutation, and an L435G mutation; and (iv) a Y344L mutation and an I347L mutation.
The specification, however, only provides the representative species of that method for performing a reverse transcription reaction for generating a nucleic acid product from an RNA template using an engineered fusion reverse transcriptase, wherein the engineered fusion reverse transcriptase comprises: (a) at least one archaeal DNA binding domain; and (b) an engineered reverse transcriptase, wherein the amino acid sequence of the engineered reverse transcriptase comprises the amino acid sequence of SEQ ID NO:7 and an M39 mutation, an L435 mutation, a D449 mutation, a D524 mutation, an E607 mutation, a D653 mutation and an L671 mutation as indexed to SEQ ID NO:7, and further comprises a second combination of mutations indexed to SEQ ID NO:7 selected from the group consisting of: (i) an E69K mutation, an E302R mutation, a T306K mutation, a W313F mutation, an L435G mutation, and an N454K mutation, and further comprising at least one mutation selected from the group consisting of an M39V mutation, an M66L mutation, an L139P mutation, an F 155Y mutation, a D200N mutation, an E201Q mutation, a T287A mutation, a T330P mutation, an R411F mutation, a P448A mutation, a D449G mutation, an H503V mutation, an H594K mutation, L603W mutation, an E607K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (ii) an L139P mutation, a D200N mutation, a T330P mutation, an L603W mutation, and an E607K mutation, and further comprising at least one mutation selected from the group consisting of: an M39V mutation, an M66L mutation, an E69K mutation, an F155Y mutation, an E2010 mutation, a T287A mutation, an E302R mutation, a T306K mutation, a W313F mutation, an R411F mutation, an L435G mutation, a P448A mutation, a D449G mutation, an N454K mutation, an H503V mutation, an H594K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (iii) an A32V mutation, an L72R mutation, a D200C mutation, a G248C mutation, an E286R mutation, an E302R mutation, a W388R mutation, and an L435G mutation; and (iv) a Y344L mutation and an I347L mutation, 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 fusion 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) 32 is rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for that method for performing a reverse transcription reaction for generating a nucleic acid product from an RNA template using an engineered fusion reverse transcriptase, wherein the engineered fusion reverse transcriptase comprises: (a) at least one archaeal DNA binding domain; and (b) an engineered reverse transcriptase, wherein the amino acid sequence of the engineered reverse transcriptase comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:7 and an M39 mutation, an L435 mutation, a D449 mutation, a D524 mutation, an E607 mutation, a D653 mutation and an L671 mutation as indexed to SEQ ID NO:7, and further comprises a second combination of mutations indexed to SEQ ID NO:7 selected from the group consisting of: (i) an E69K mutation, an E302R mutation, a T306K mutation, a W313F mutation, an L435G mutation, and an N454K mutation, and further comprising at least one mutation selected from the group consisting of an M39V mutation, an M66L mutation, an L139P mutation, an F 155Y mutation, a D200N mutation, an E201Q mutation, a T287A mutation, a T330P mutation, an R411F mutation, a P448A mutation, a D449G mutation, an H503V mutation, an H594K mutation, L603W mutation, an E607K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (ii) an L139P mutation, a D200N mutation, a T330P mutation, an L603W mutation, and an E607K mutation, and further comprising at least one mutation selected from the group consisting of: an M39V mutation, an M66L mutation, an E69K mutation, an F155Y mutation, an E2010 mutation, a T287A mutation, an E302R mutation, a T306K mutation, a W313F mutation, an R411F mutation, an L435G mutation, a P448A mutation, a D449G mutation, an N454K mutation, an H503V mutation, an H594K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (iii) an A32V mutation, an L72R mutation, a D200C mutation, a G248C mutation, an E286R mutation, an E302R mutation, a W388R mutation, and an L435G mutation; and (iv) a Y344L mutation and an I347L mutation, does not reasonably provide enablement for all possible methods for performing a reverse transcription reaction for generating a nucleic acid product from an RNA template using an engineered fusion reverse transcriptase, wherein the engineered fusion reverse transcriptase comprises: (a) at least one archaeal DNA binding domain; and (b) an engineered reverse transcriptase, wherein the amino acid sequence of the engineered fusion reverse transcriptase comprises an M39 mutation, an L435 mutation, a D449 mutation, a D524 mutation, an E607 mutation, a D653 mutation and an L671 mutation as indexed to SEQ ID NO:7, and further comprises a second combination of mutations indexed to SEQ ID NO:7 selected from the group consisting of: (i) an E69K mutation, an E302R mutation, a T306K mutation, a W313F mutation, an L435G mutation, and an N454K mutation, and further comprising at least one mutation selected from the group consisting of an M39V mutation, an M66L mutation, an L139P mutation, an F 155Y mutation, a D200N mutation, an E201Q mutation, a T287A mutation, a T330P mutation, an R411F mutation, a P448A mutation, a D449G mutation, an H503V mutation, an H594K mutation, L603W mutation, an E607K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (ii) an L139P mutation, a D200N mutation, a T330P mutation, an L603W mutation, and an E607K mutation, and further comprising at least one mutation selected from the group consisting of: an M39V mutation, an M66L mutation, an E69K mutation, an F155Y mutation, an E2010 mutation, a T287A mutation, an E302R mutation, a T306K mutation, a W313F mutation, an R411F mutation, an L435G mutation, a P448A mutation, a D449G mutation, an N454K mutation, an H503V mutation, an H594K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (iii) an A32V mutation, an L72R mutation, a D200C mutation, a G248C mutation, an E286R mutation, an E302R mutation, a W388R mutation, and an L435G mutation; and (iv) a Y344L mutation and an I347L mutation. 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) 32 is so broad as to encompass all possible methods for performing a reverse transcription reaction for generating a nucleic acid product from an RNA template using an engineered fusion reverse transcriptase, wherein the engineered fusion reverse transcriptase comprises: (a) at least one archaeal DNA binding domain; and (b) an engineered reverse transcriptase, wherein the amino acid sequence of the engineered fusion reverse transcriptase comprises an M39 mutation, an L435 mutation, a D449 mutation, a D524 mutation, an E607 mutation, a D653 mutation and an L671 mutation as indexed to SEQ ID NO:7, and further comprises a second combination of mutations indexed to SEQ ID NO:7 selected from the group consisting of: (i) an E69K mutation, an E302R mutation, a T306K mutation, a W313F mutation, an L435G mutation, and an N454K mutation, and further comprising at least one mutation selected from the group consisting of an M39V mutation, an M66L mutation, an L139P mutation, an F 155Y mutation, a D200N mutation, an E201Q mutation, a T287A mutation, a T330P mutation, an R411F mutation, a P448A mutation, a D449G mutation, an H503V mutation, an H594K mutation, L603W mutation, an E607K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (ii) an L139P mutation, a D200N mutation, a T330P mutation, an L603W mutation, and an E607K mutation, and further comprising at least one mutation selected from the group consisting of: an M39V mutation, an M66L mutation, an E69K mutation, an F155Y mutation, an E2010 mutation, a T287A mutation, an E302R mutation, a T306K mutation, a W313F mutation, an R411F mutation, an L435G mutation, a P448A mutation, a D449G mutation, an N454K mutation, an H503V mutation, an H594K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (iii) an A32V mutation, an L72R mutation, a D200C mutation, a G248C mutation, an E286R mutation, an E302R mutation, a W388R mutation, and an L435G mutation; and (iv) a Y344L mutation and an I347L mutation. The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of engineered fusion reverse transcriptases, variants and methods of use broadly encompassed by the claims. The claims rejected under this section of U.S.C. 112, first paragraph, place minimal structural limits on the engineered fusion 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 the engineered fusion reverse transcriptase having the amino acid sequence of SEQ ID N0: 7 and the specified mutations.
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 methods for performing a reverse transcription reaction for generating a nucleic acid product from an RNA template using an engineered fusion reverse transcriptase, wherein the engineered fusion reverse transcriptase comprises: (a) at least one archaeal DNA binding domain; and (b) an engineered reverse transcriptase, wherein the amino acid sequence of the engineered reverse transcriptase comprises an M39 mutation, an L435 mutation, a D449 mutation, a D524 mutation, an E607 mutation, a D653 mutation and an L671 mutation as indexed to SEQ ID NO:7, and further comprises a second combination of mutations indexed to SEQ ID NO:7 selected from the group consisting of: (i) an E69K mutation, an E302R mutation, a T306K mutation, a W313F mutation, an L435G mutation, and an N454K mutation, and further comprising at least one mutation selected from the group consisting of an M39V mutation, an M66L mutation, an L139P mutation, an F 155Y mutation, a D200N mutation, an E201Q mutation, a T287A mutation, a T330P mutation, an R411F mutation, a P448A mutation, a D449G mutation, an H503V mutation, an H594K mutation, L603W mutation, an E607K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (ii) an L139P mutation, a D200N mutation, a T330P mutation, an L603W mutation, and an E607K mutation, and further comprising at least one mutation selected from the group consisting of: an M39V mutation, an M66L mutation, an E69K mutation, an F155Y mutation, an E2010 mutation, a T287A mutation, an E302R mutation, a T306K mutation, a W313F mutation, an R411F mutation, an L435G mutation, a P448A mutation, a D449G mutation, an N454K mutation, an H503V mutation, an H594K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (iii) an A32V mutation, an L72R mutation, a D200C mutation, a G248C mutation, an E286R mutation, an E302R mutation, a W388R mutation, and an L435G mutation; and (iv) a Y344L mutation and an I347L mutation, because the specification does not establish: (A) regions of the engineered fusion reverse transcriptase which may be modified effecting the reverse transcriptase activity; (B) the general tolerance of engineered fusion reverse transcriptases to modification and extent of such tolerance; (C) a rational and predictable scheme for modifying any amino acid residue of an engineered fusion 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 methods of use of the engineered fusion 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 possible methods for performing a reverse transcription reaction for generating a nucleic acid product from an RNA template using an engineered fusion reverse transcriptase, wherein the engineered fusion reverse transcriptase comprises: (a) at least one archaeal DNA binding domain; and (b) an engineered reverse transcriptase, wherein the amino acid sequence of the engineered fusion reverse transcriptase comprises an M39 mutation, an L435 mutation, a D449 mutation, a D524 mutation, an E607 mutation, a D653 mutation and an L671 mutation as indexed to SEQ ID NO:7, and further comprises a second combination of mutations indexed to SEQ ID NO:7 selected from the group consisting of: (i) an E69K mutation, an E302R mutation, a T306K mutation, a W313F mutation, an L435G mutation, and an N454K mutation, and further comprising at least one mutation selected from the group consisting of an M39V mutation, an M66L mutation, an L139P mutation, an F 155Y mutation, a D200N mutation, an E201Q mutation, a T287A mutation, a T330P mutation, an R411F mutation, a P448A mutation, a D449G mutation, an H503V mutation, an H594K mutation, L603W mutation, an E607K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (ii) an L139P mutation, a D200N mutation, a T330P mutation, an L603W mutation, and an E607K mutation, and further comprising at least one mutation selected from the group consisting of: an M39V mutation, an M66L mutation, an E69K mutation, an F155Y mutation, an E2010 mutation, a T287A mutation, an E302R mutation, a T306K mutation, a W313F mutation, an R411F mutation, an L435G mutation, a P448A mutation, a D449G mutation, an N454K mutation, an H503V mutation, an H594K mutation, an H634Y mutation, a G637R mutation and an H638G mutation; (iii) an A32V mutation, an L72R mutation, a D200C mutation, a G248C mutation, an E286R mutation, an E302R mutation, a W388R mutation, and an L435G mutation; and (iv) a Y344L mutation and an I347L mutation. 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 fusion reverse transcriptases and methods of use 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 § 103
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 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.
Claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. ( US 8,828,700), Kowalczykowski et al. (US 7,666,591) and Lee et al. (WO 2018/200867).
Lee et al. ( US 8,828,700) teach fusion proteins comprising a single strand DNA binding protein and a nucleic acid polymerase (e.g. DNA polymerase or reverse transcriptase) (see claims 1-3 and supporting text). Lee et al. ( US 8,828,700) teach these high fidelity proteins are suitable for use in nucleic acid amplification methods, including the polymerase chain reaction (PCR), especially reverse transcriptase polymerase chain reaction (RT-PCR). Lee et al. ( US 8,828,700) further teach the above single stranded DNA binding proteins (SSBs) are proteins that preferentially bind single stranded DNA (ssDNA) over double-stranded DNA in a nucleotide sequence independent manner. Lee et al. ( US 8,828,700) further teach the above reverse transcriptases of the fusion can be any of a number of reverse transcriptases such as M-MLV reverse transcriptase (column 4 line 64-column 5, line 33).
Kowalczykowski et al. (US 7,666,591) teach a number of single stranded DNA binding proteins from Archaea and their uses in a variety of biotechnical processes including polymerase chain reaction (PCR). Kowalczykowski et al. (US 7,666,591) teach a number of ssDNA-binding protein from the genomes of several archaeons. Kowalczykowski et al. (US 7,666,591) teach nucleic acid sequences encoding an ssDNA-binding protein from an several Archaeon, including Methanococcus jannaschii, Methanobacter theromoautotrophicum, and Archaeoglobus fulgidus.
Lee et al. (WO 2018/200867) teach engineered reverse transcription enzymes that exhibit several desired properties such as thermal stability, processive reverse transcription, non-templated base addition, and template switching ability (see abstract and supporting text). The engineered reverse transcription enzymes described by Lee et al. (WO 2018/200867) demonstrate unexpectedly higher resistance to cell lysate inhibition, greater ability to capture full-length mRNA transcripts, and demonstrate improved results in small reaction volumes as compared to other engineered reverse transcription enzymes. Lee et al. (WO 2018/200867) teach a mutant MMLV reverse transcriptase comprising SEQ ID NO:3 (which has greater than 90% sequence identity to instant SEQ ID NO:1) and a L435 mutation, a D449 mutation, a D524 mutation, and an E607 mutation, wherein said mutant reverse transcriptase has improved ability to capture full-length transcripts and higher resistance to cell lysates. Lee et al. (WO 2018/200867) further teach methods of performing a reverse transcriptase reaction for generating a nucleic acid comprising using the above mutant reverse transcriptases (see claims 22-26 and supporting text).
One of skill in the art before the effective filing date would have been motivated to substitute the single stranded DNA binding proteins from Archaea as taught by Kowalczykowski et al. (US 7,666,591) and the mutant MMLV reverse transcriptase comprising SEQ ID NO:3 and a L435 mutation, a D449 mutation, a D524 mutation, and an E607 mutation, as taught by Lee et al. (WO 2018/200867) in the fusion proteins comprising a single strand DNA binding protein and a reverse transcriptase taught by Lee et al. ( US 8,828,700) as a means of improving the methods of nucleic acid amplification through reverse transcriptase. The motivation for the substitution of the single stranded DNA binding proteins from Archaea as taught by Kowalczykowski et al. (US 7,666,591) in the fusion proteins comprising a single strand DNA binding protein and a reverse transcriptase taught by Lee et al. ( US 8,828,700) is that Lee et al. ( US 8,828,700) teach that any single stranded DNA binding protein can be substituted in the fusions and Kowalczykowski et al. (US 7,666,591) teach single stranded DNA binding proteins having the same single stranded DNA binding activities. The motivation for the substitution of the mutant MMLV reverse transcriptase comprising SEQ ID NO:3 and a L435 mutation, a D449 mutation, a D524 mutation, and an E607 mutation, taught by Lee et al. (WO 2018/200867) in the fusion proteins comprising a single strand DNA binding protein and a reverse transcriptase taught by Lee et al. ( US 8,828,700) is that is that Lee et al. ( US 8,828,700) teach that any reverse transcriptase can be substituted in the fusions and Lee et al. (WO 2018/200867) teach that the mutant MMLV reverse transcriptase comprising SEQ ID NO:3 and a L435 mutation, a D449 mutation, a D524 mutation, and an E607 mutation have improved has improved activities such as the ability to capture full-length transcripts and higher resistance to cell lysates. The expectation of success is high based upon the high level of skill in the art of recombinant DNA and protein engineering as exemplified by Lee et al. ( US 8,828,700), Kowalczykowski et al. (US 7,666,591) and Lee et al. (WO 2018/200867) who teach all the materials and methodology required to make and use the obvious engineered fusion reverse transcriptase comprising an archaeal DNA binding domain; an engineered reverse transcriptase having an amino acid sequence that is at least 90% identical to SEQ ID NO: 1, wherein said engineered reverse transcriptase comprises an L435 mutation, a D449 mutation, a D524 mutation, and an E607 mutation, as indexed to SEQ ID NO:7.
Thus, claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. ( US 8,828,700), Kowalczykowski et al. (US 7,666,591) and Lee et al. (WO 2018/200867).
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 28-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 67 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 claim 67 of copending Application No. 18/744,254 (reference application) drawn to method of using the 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 28-32 drawn to a method for performing a reverse transcription reaction for generating a nucleic acid product from an RNA template using [[an]]the engineered fusion reverse transcriptase comprising:
(a) at least one archaeal DNA binding domain; and (b) an engineered reverse transcriptase having an amino acid sequence that is at least 90% identical to SEQ ID NO: 1, wherein said engineered reverse transcriptase comprises an L435 mutation, a D449 mutation, a D524 mutation, and an E607 mutation, as indexed to SEQ ID NO:7.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Remarks
No claim is allowed.
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rgh
3/30/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652