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 .
Applicant’s cancellation of claims 1-5, 9-12, 15-17, 19, 21, amendment of claim 28-30, 32, and the addition of new claims 36-41, in the paper of 6/30/2026, is
acknowledged. Applicants' arguments filed on 6/30/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 28-32 and 36-41 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
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 28-32, 36-41 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.
Newly amended claim 28 (claims 29-32, 36-41 dependent from) is indefinite in that in that it is unclear as to whether newly added part (a) and (b) are intended to limit the engineered fusion reverse transcriptase or the method for performing a reverse transcriptase reaction. In the interest of advancing prosecution parts (a) and (b) are interpreted as limitations of the engineered fusion reverse transcriptase and not the method for performing a reverse transcriptase reaction.
Claim 31 is indefinite because it is drawn to the method of claim 28, wherein the engineered fusion reverse transcriptase comprises the amino acid sequence of SEQ ID NO:1. This is indefinite in that SEQ ID NO:1 comprises a methionine at position 39 but claim 28 from which claim 31 depends requires that the methionine at position 39 be mutated.
Newly added claim 38 is indefinite because it is drawn to the method of claim 28, wherein the engineered fusion reverse transcriptase comprises the amino acid sequence of SEQ ID NO:1. This is indefinite in that SEQ ID NO:1 comprises a methionine at position 39 but claim 28 from which claim 38 depends requires that the methionine at position 39 be mutated. Similarly claim SEQ ID NO:1 comprises an D653, which must be mutated as par claim 28. Similarly claim SEQ ID NO:1 comprises an L671 which must be mutated as par claim 28Similarly claim SEQ ID NO:1 comprises an D653, which must be mutated as par claim 28. Thus claim 30 conflicts with claim 28 from which it depends.
Appropriate correction and/or comment is required.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 31 and 38 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
As stated above, newly added claims 31 and 38 are indefinite in that they are drawn to the method of claim 28, wherein the engineered fusion reverse transcriptase comprises the amino acid sequence of SEQ ID NO:3 (claim 31) or SEQ ID NO:1 (claim 38). These claims improperly depend from claim 28 because SEQ ID NO:3 (claim 31) and SEQ ID NO:1 (claim 38) comprise a methionine at position 39 but claim 28, from which claims 31 and 38 depend, requires that the methionine at position 39 be mutated.
Applicants may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
The rejection of 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) is withdrawn based upon applicants amendment of the claims in the paper of 6/30/2026.
Claim(s) 28-32, 36, 37-41 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 Clark et al. (WO 2021/119320).
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.
Clark et al. (WO 2021/119320) 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 Clark et al. (WO 2021/119320) 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. Clark et al. (WO 2021/119320) 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 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, wherein said mutant reverse transcriptase has improved ability to capture full-length transcripts and higher resistance to cell lysates. Clark et al. (WO 2021/119320) further teach methods of performing a reverse transcriptase reaction for generating a nucleic acid comprising using the above mutant reverse transcriptases (see claims 2-10 and supporting text). Clark et al. (WO 2021/119320) teach additional mutant MMLV reverse transcriptase comprising SEQ ID NO:3 (which has greater than 90% sequence identity to instant SEQ ID NO:1) and a an E69 mutation, an L139 mutation, a D200 mutation, an E302 mutation, a T306 mutation, a W313 mutation, a T330 mutation, a P448 mutation, an N454 mutation, and an L603 mutation, as indexed to SEQ ID NO:7. Clark et al. (WO 2021/119320) further teach the following mutations E69K mutation, an E302R mutation, a T306K mutation, a W313F mutation, an L435G mutation, an N454K mutation, M39V mutation, an M66L mutation, an L139P mutation, an F155Y 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, H638G mutation; an L139P mutation, a D200N mutation, a T330P mutation, an L603W mutation, an E607K mutation, an M39V mutation, an M66L mutation, an E69K mutation, an F155Y mutation, an E201Q 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, an H638G mutation; an A32V mutation, an L72R mutation, a D200C mutation, a G248C mutation, an E286R mutation, an E302R mutation, a W388R mutation, an L435G mutation; and a Y344L as well as combinations of the above and others.
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 (which has greater than 90% sequence identity to instant SEQ ID NO:1) and a 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, as taught by Clark et al. (WO 2021/119320) 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 Clark et al. (WO 2021/119320) 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 mutant MMLV reverse transcriptase comprising SEQ ID NO:3 (which has greater than 90% sequence identity to instant SEQ ID NO:1) and a 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, taught by Clark et al. (WO 2021/119320) 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 Clark et al. (WO 2021/119320) teach that the mutant MMLV reverse transcriptase comprising SEQ ID NO:3 (which has greater than 90% sequence identity to instant SEQ ID NO:1) and a 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 have 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 Clark et al. (WO 2021/119320) who teach all the materials and methodology required to make and use the obvious engineered fusion reverse transcriptase comprising an archaeal DNA binding domain and 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 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.
Thus, claim(s) 28-32, 36, 37-41 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 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 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.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicants are reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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
8/20/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
Prosecution Insights