DETAILED ACTION
Notice of Pre-AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election of Group I, claims 33-34 and 41-42 in the reply filed on 05 December 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Status of Application
Claims 33-52 are pending; Claims 35-40 and 43-52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Thus, claims 33-34 and 41-42 are subject to examination on the merits.
Priority
The instant application is a CON of US 16358609 (US Patent 11485959), which is a CON of US 15221777 (US Patent 10287559), which is a CON of US 13774718 (US Patent 9546382) which is a DIV of US 12712504 (US Patent 8399643), which claims benefit of US Provisional 61155804 filed 26 February 2009.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05 December 2025 and 22 August 2023 have been considered by the examiner. See initialed and signed PTO/SB/08’s.
Claim Objections
Claim 33 is objected to because of the following informalities: the word “proline” is misspelled twice in the claim as “pro line”, lines 8 and 17. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – 2nd paragraph
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 41 and 42 are rejected under 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 applicant regards as the invention.
Claim 41 recites “wherein the hyperactive transposase protein further comprises an amino acid substitution at positions 30, 165 and 282, wherein the substitution at position 30 is a substitution of a Valine for an Isoleucine (I30V), and wherein the substitution at position 165 is a substitution of a Serine for a Glycine (G165S).”
The claim construction is ambiguous as to whether or not only one of the substitutions at positions 30, 165 or 282 is necessary. That is, “comprises an amino acid substitution”, suggests only one of the three substitutions is necessary. But then the claim also recites “comprises an amino acid substitution at positions 30, 165 and 282”. The plural “positions” as well as an “and” suggests all three may be required. Clarification and amendments are requested. Claim 42 is included as it does not remedy the noted deficiency.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 33-34 and 41-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 8399643. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘643 patent render the instant claims obvious.
The instant claims in their broadest are drawn to: a hyperactive transposase protein comprising an amino acid sequence having at least 90% amino acid sequence identity to the protein encoded by the nucleotide sequence of SEQ ID NO: 1 and comprising at least one of the following amino acid substitutions as compared to the protein encoded by the nucleotide sequence of SEQ ID NO: 1: an asparagine for the serine at position 3; a valine for the isoleucine at position 30; a serine for the alanine at position 46; a threonine for the alanine at position 46; a tryptophan for the isoleucine at position 82; a proline for the serine at position 103; a pro line for the arginine at position 119; an alanine for the cysteine at position 125; a leucine for the cysteine at position 125; a serine for the glycine at position 165; a lysine for the tyrosine at position 177; a histidine for the tyrosine at position 177; a leucine for the phenylalanine at position 180; an isoleucine for the phenylalanine at position 180; a valine for the phenylalanine at position 180; a leucine for the methionine at position 185; a glycine for the alanine at position 187; a tryptophan for the phenylalanine at position 200; a proline for the valine at position 207; a phenylalanine for the valine at position 209; a phenylalanine for the methionine at position 226; an arginine for the leucine at position 235; a lysine for the valine at position 240; a leucine for the phenylalanine at position 241; a lysine for the pro line at position 243; a serine for the asparagine at position 258; a glutamine for the methionine at position 282; a tryptophan for the leucine at position 296; a tyrosine for the leucine at position 296; a phenylalanine for the leucine at position 296; a leucine for the methionine at position 298; an alanine for the methionine at position 298; a valine for the methionine at position 298; an isoleucine for the proline at position 311; a valine for the proline at position 311; a lysine for the arginine at position 315; a glycine for the threonine at position 319; an arginine for the tyrosine at position 327; a valine for the tyrosine at position 328; a glycine for the cysteine at position 340; a leucine for the cysteine at position 340; a histidine for the aspartic acid at position 421; an isoleucine for the valine at position 436; a tyrosine for the methionine at position 456; a phenylalanine for the leucine at position 470; a lysine for the serine at position 486; a leucine for the methionine at position 503; an isoleucine for the methionine at position 503; a lysine for the valine at position 552; a threonine for the alanine at position 570; a proline for the glutamine at position 591; or an arginine for the glutamine at position 591.
The claims to the ‘643 patent in their broadest are drawn to an isolated nucleic acid encoding a protein comprising at least 90% sequence identity to SEQ ID NO:2, and comprising at least one of the following amino acid substitutions in SEQ ID NO:2: a serine for the alanine at position 46; a threonine for the alanine at position 46; a proline for the arginine at position 119; an alanine for the cysteine at position 125; a leucine for the cysteine at position 125; a lysine for the tyrosine at position 177; a histidine for the tyrosine at position 177; a leucine for the phenylalanine at position 180; an isoleucine for the phenylalanine at position 180; a valine for the phenylalanine at position 180; a leucine for the methionine at position 185; a glycine for the alanine at position 187; a tryptophan for the phenylalanine at position 200; a proline for the valine at position 207; a phenylalanine for the valine at position 209; a phenylalanine for the methionine at position 226; an arginine for the leucine at position 235; a lysine for the valine at position 240; a leucine for the phenylalanine at position 241; a lysine for the proline at position 243; a glutamine for the methionine at position 282; a tryptophan for the leucine at position 296; a tyrosine for the leucine at position 296; a phenylalanine for the leucine at position 296; a leucine for the methionine at position 298; an alanine for the methionine at position 298; a valine for the methionine at position 298; an isoleucine for the proline at position 311; a valine for the proline at position 311; a lysine for the arginine at position 315; a glycine for the threonine at position 319; an arginine for the tyrosine at position 327; a valine for the tyrosine at position 328; a glycine for the cysteine at position 340; a leucine for the cysteine at position 340; a histidine for the aspartic acid at position 421; an isoleucine for the valine at position 436; a tyrosine for the methionine at position 456; a phenylalanine for the leucine at position 470; a lysine for the serine at position 486; a leucine for the methionine at position 503; an isoleucine for the methionine at position 503; a lysine for the valine at position 552; a threonine for the alanine at position 570.
Thus, the claims differ on two matters: First, the claims to the ‘643 patent are drawn to nucleic acids encoding a transposase having at least 90% amino acid sequence identity to SEQ ID NO: 2. The instant claims, however, are drawn to hyperactive piggybac transposase encoded by a nucleic acid sequence, the encoded transposase having at least 90% amino acid sequence identity to SEQ ID NO: 2. Thus, the claims differ in that the nucleic acids encoding SEQ ID NO: 2 having 90% identity thereto and specific substitutions. Nonetheless, the nucleic acids encode the same proteins/transposases with the same amino acid sequences. The nucleic acids are thus an obvious variation of because they encode the transposase with the same/overlapping substitutions. The second difference between the sets of claims is the instant claims recite an additional seven amino acid substitutions to choose from (those underlined above). Nonetheless, every substitution recited in the ‘643 patent claims are recited in the instant claims and given both sets of claims recite the transposase/encoded transposase has at least one substitution selected from 44 out 51 of the same substitutions, then this renders the selected positions as obvious.
It is noted, instant SEQ ID NO: 1 encodes a protein having 99.8% sequence identity to SEQ ID NO: 2 of the ‘643 patent, there being a single mismatch at amino acid 303 - See Supplemental Content, file 20260122_085950_us-18-051-109a-1.rai, Result #6, there being a Tyr at this position. In SEQ ID NO: 2, position 303 is a Tyr. It is noted, however, the codon “ACC” does not encode Tyr, instead it encodes Thr. This seems to be a peristent inconsistency/error throughout the family of patents.
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For example, in the sequence listing in the 13774718 child application also shows this in the sequence listing for SEQ ID NO: 1 and its supposed encoded amino acid sequence.
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Again, “ACC” does not encode Tyr, it encodes Thr.
Instant SEQ ID NO: 1 supposedly encodes instant SEQ ID NO: 2, but there is Tyr at instant amino acid 303 (throughout the entire patent family for SEQ ID NO: 2) and not a Thr.
Nonetheless, even with a Tyr at position 303 instead of Thr, the encoded amino acid sequence of the instant claims has 99.8% sequence identity with SEQ ID NO: 2 of the ‘643 patent.
Finally, with regard to a NLS as in claim 34, while the patented claims do not recite said NLS, it is clear when construing the scope of the patented claims in understanding a hyperactive piggybac transposase and as defined in the specification (See MPEP 804(II)(B)(1)), NLS sequences are clearly envisaged – See Col. 27, lines 42-67).
Claims 33-34 and 41-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 9546382. Although the claims at issue are not identical, they are not patentably distinct from each other because the expressed proteins of the ‘382 patent claims render obvious the instant claims.
The instant claims in their broadest are drawn to: a hyperactive transposase protein comprising an amino acid sequence having at least 90% amino acid sequence identity to the protein encoded by the nucleotide sequence of SEQ ID NO: 1 and comprising at least one of the following amino acid substitutions as compared to the protein encoded by the nucleotide sequence of SEQ ID NO: 1: an asparagine for the serine at position 3; a valine for the isoleucine at position 30; a serine for the alanine at position 46; a threonine for the alanine at position 46; a tryptophan for the isoleucine at position 82; a proline for the serine at position 103; a pro line for the arginine at position 119; an alanine for the cysteine at position 125; a leucine for the cysteine at position 125; a serine for the glycine at position 165; a lysine for the tyrosine at position 177; a histidine for the tyrosine at position 177; a leucine for the phenylalanine at position 180; an isoleucine for the phenylalanine at position 180; a valine for the phenylalanine at position 180; a leucine for the methionine at position 185; a glycine for the alanine at position 187; a tryptophan for the phenylalanine at position 200; a proline for the valine at position 207; a phenylalanine for the valine at position 209; a phenylalanine for the methionine at position 226; an arginine for the leucine at position 235; a lysine for the valine at position 240; a leucine for the phenylalanine at position 241; a lysine for the pro line at position 243; a serine for the asparagine at position 258; a glutamine for the methionine at position 282; a tryptophan for the leucine at position 296; a tyrosine for the leucine at position 296; a phenylalanine for the leucine at position 296; a leucine for the methionine at position 298; an alanine for the methionine at position 298; a valine for the methionine at position 298; an isoleucine for the proline at position 311; a valine for the proline at position 311; a lysine for the arginine at position 315; a glycine for the threonine at position 319; an arginine for the tyrosine at position 327; a valine for the tyrosine at position 328; a glycine for the cysteine at position 340; a leucine for the cysteine at position 340; a histidine for the aspartic acid at position 421; an isoleucine for the valine at position 436; a tyrosine for the methionine at position 456; a phenylalanine for the leucine at position 470; a lysine for the serine at position 486; a leucine for the methionine at position 503; an isoleucine for the methionine at position 503; a lysine for the valine at position 552; a threonine for the alanine at position 570; a proline for the glutamine at position 591; or an arginine for the glutamine at position 591.
The claims to the ‘382 patent in their broadest are drawn to: a non-human, transgenic animal whose genome comprises a nucleic acid molecule encoding a protein comprising at least 90% sequence identity to SEQ ID NO:2, and comprising at least one of the following amino acid substitutions in SEQ ID NO:2: a serine for the alanine at position 46; a threonine for the alanine at position 46; a proline for the arginine at position 119; an alanine for the cysteine at position 125; a leucine for the cysteine at position 125; a lysine for the tyrosine at position 177; a histidine for the tyrosine at position 177; a leucine for the phenylalanine at position 180; an isoleucine for the phenylalanine at position 180; a valine for the phenylalanine at position 180; a leucine for the methionine at position 185; a glycine for the alanine at position 187; a tryptophan for the phenylalanine at position 200; a proline for the valine at position 207; a phenylalanine for the valine at position 209; a phenylalanine for the methionine at position 226; an arginine for the leucine at position 235; a lysine for the valine at position 240; a leucine for the phenylalanine at position 241; a lysine for the proline at position 243; a glutamine for the methionine at position 282; a tryptophan for the leucine at position 296; a tyrosine for the leucine at position 296; a phenylalanine for the leucine at position 296; a leucine for the methionine at position 298; an alanine for the methionine at position 298; a valine for the methionine at position 298; an isoleucine for the proline at position 311; a valine for the proline at position 311; a lysine for the arginine at position 315; a glycine for the threonine at position 319; an arginine for the tyrosine at position 327; a valine for the tyrosine at position 328; a glycine for the cysteine at position 340; a leucine for the cysteine at position 340; a histidine for the aspartic acid at position 421; an isoleucine for the valine at position 436; a tyrosine for the methionine at position 456; a phenylalanine for the leucine at position 470; a lysine for the serine at position 486; a leucine for the methionine at position 503; an isoleucine for the methionine at position 503; a lysine for the valine at position 552; or a threonine for the alanine at position 570, operably linked to a promoter, wherein the protein is expressed.
Dependent claims recite, for example, generating non-human, transgenic animals by germline mutation, wherein the non-human, transgenic animals comprise cells comprising vectors comprising vectors encoding the transposases as above (See claim 11).
Thus, the claims differ on two matters: First, the claims to the ‘382 patent are drawn to non-human, transgenic animals whose genomes comprise nucleic acids encoding a transposase having at least 90% amino acid sequence identity to SEQ ID NO: 2. The instant claims, however, are drawn to hyperactive piggybac transposase encoded by a nucleic acid sequence, the encoded transposase having at least 90% amino acid sequence identity to SEQ ID NO: 2. Thus, the claims differ in that the cells comprise nucleic acids encoding SEQ ID NO: 2 having 90% identity thereto and specific substitutions. Nonetheless, both nucleic acids encode the same proteins/transposases with the same amino acid sequences. The nucleic acids are thus an obvious variation of because they encode the transposase with the same/overlapping substitutions. The second difference between the sets of claims is the instant claims recite an additional seven amino acid substitutions to choose from (those underlined above). Nonetheless, every substitution recited in the ‘382 patent claims are recited in the instant claims and given both sets of claims recite the transposase/encoded transposase has at least one substitution selected from 44 out 51 of the same substitutions, then this renders the selected positions as obvious.
It is noted, instant SEQ ID NO: 1 encodes a protein having 99.8% sequence identity to SEQ ID NO: 2 of the ‘382 patent, there being a single mismatch at amino acid 303 - See Supplemental Content, file 20260122_085950_us-18-051-109a-1.rai, Duplicates for Result #6, there being a Tyr at this position. In SEQ ID NO: 2, position 303 is a Tyr. It is noted, however, the codon “ACC” does not encode Tyr, instead it encodes Thr. This seems to be a peristent inconsistency/error throughout the family of patents.
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For example, in the sequence listing of this patent, shows this in the sequence listing for SEQ ID NO: 1 and its supposed encoded amino acid sequence.
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Again, “ACC” does not encode Tyr, it encodes Thr.
Instant SEQ ID NO: 1 supposedly encodes instant SEQ ID NO: 2, but there is Tyr at instant amino acid 303 (throughout the entire patent family for SEQ ID NO: 2) and not a Thr.
Nonetheless, even with a Tyr at position 303 instead of Thr, the encoded amino acid sequence of the instant claims has 99.8% sequence identity with SEQ ID NO: 2 of the ‘382 patent.
Finally, with regard to a NLS as in claim 34, while the patented claims do not recite said NLS, it is clear when construing the scope of the patented claims in understanding a hyperactive piggybac transposase and as defined in the specification (See MPEP 804(II)(B)(1)), NLS sequences are clearly envisaged – See Col. 28, lines 40-67).
Claims 33-34 and 41-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10287559. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims to the 559’ patent render obvious the instant claims.
The instant claims in their broadest are drawn to: a hyperactive transposase protein comprising an amino acid sequence having at least 90% amino acid sequence identity to the protein encoded by the nucleotide sequence of SEQ ID NO: 1 and comprising at least one of the following amino acid substitutions as compared to the protein encoded by the nucleotide sequence of SEQ ID NO: 1: an asparagine for the serine at position 3; a valine for the isoleucine at position 30; a serine for the alanine at position 46; a threonine for the alanine at position 46; a tryptophan for the isoleucine at position 82; a proline for the serine at position 103; a pro line for the arginine at position 119; an alanine for the cysteine at position 125; a leucine for the cysteine at position 125; a serine for the glycine at position 165; a lysine for the tyrosine at position 177; a histidine for the tyrosine at position 177; a leucine for the phenylalanine at position 180; an isoleucine for the phenylalanine at position 180; a valine for the phenylalanine at position 180; a leucine for the methionine at position 185; a glycine for the alanine at position 187; a tryptophan for the phenylalanine at position 200; a proline for the valine at position 207; a phenylalanine for the valine at position 209; a phenylalanine for the methionine at position 226; an arginine for the leucine at position 235; a lysine for the valine at position 240; a leucine for the phenylalanine at position 241; a lysine for the pro line at position 243; a serine for the asparagine at position 258; a glutamine for the methionine at position 282; a tryptophan for the leucine at position 296; a tyrosine for the leucine at position 296; a phenylalanine for the leucine at position 296; a leucine for the methionine at position 298; an alanine for the methionine at position 298; a valine for the methionine at position 298; an isoleucine for the proline at position 311; a valine for the proline at position 311; a lysine for the arginine at position 315; a glycine for the threonine at position 319; an arginine for the tyrosine at position 327; a valine for the tyrosine at position 328; a glycine for the cysteine at position 340; a leucine for the cysteine at position 340; a histidine for the aspartic acid at position 421; an isoleucine for the valine at position 436; a tyrosine for the methionine at position 456; a phenylalanine for the leucine at position 470; a lysine for the serine at position 486; a leucine for the methionine at position 503; an isoleucine for the methionine at position 503; a lysine for the valine at position 552; a threonine for the alanine at position 570; a proline for the glutamine at position 591; or an arginine for the glutamine at position 591. Dependent claim 41 recites the hyperactive piggybac transposase of claim 33, comprises an amino acid substitution at positions 30, 165 and 282, wherein the substitution at position 30 is a substitution of a Valine for an Isoleucine (I30V), and wherein the substitution at position 165 is a substitution of a Serine for a Glycine (G165S). Dependent claim 42 recites the hyperactive piggbac transposase of claim 41, wherein the substitution at position 282 is a substitution of any amino acid (X) for a Methionine (M282X), the amino acid (X) selected from the group consisting of a Leucine (L), an Isoleucine (I), a Valine (V), and an Alanine (A).
The claims to the ‘559 patent in their broadest are drawn to A hyperactive transposase protein comprising at least 90% sequence identity to SEQ ID NO: 2, and comprising: (a) an amino acid substitution at position 30 and 282, or (b) an amino acid substitution at position 165 and 282, wherein the substitution at position 30 is a substitution of a Valine for an Isoleucine (I30V), wherein the substitution at position 165 is a substitution of a Serine for a Glycine (G165S), wherein the substitution at position 282 is a substitution of any amino acid (X) for a Methionine (M282X), the amino acid (X) selected from the group consisting of a Leucine (L), an Isoleucine (I), a Valine (V), and an Alanine (A), and wherein the hyperactive transposase protein is capable of mediating transposon integration at a higher frequency when compared to a wild type transposase having the sequence of SEQ ID NO: 2. Dependent claim 2 recites nucleic acids encoding said hyperactive piggybac transposase.
Thus the difference between the ‘559 patent claims and the instant patent claims is the nucleic acid encoding the hyperactive piggybac transposase is not defined. However, the claims are not drawn to nucleic acids and therefore not limited by SEQ ID NO: 1, rather they are drawn to and limited to the encoded hyperactive transposase protein comprising SEQ ID NO: 2 or sequences having 90% identity thereto along with the requisite substitutions. Thus, claims 1 and 2 of the ‘559 would render obvious the instant claims when claims 33, 41 and 42 are combined.
It is noted, instant SEQ ID NO: 1 encodes a protein having 99.8% sequence identity to SEQ ID NO: 2 of the ‘559 patent, there being a single mismatch at amino acid 303 - See Supplemental Content, file 20260122_085950_us-18-051-109a-1.rai, Duplicates for Result #6, there being a Tyr at this position. In SEQ ID NO: 2, position 303 is a Tyr. It is noted, however, the codon “ACC” does not encode Tyr, instead it encodes Thr. This seems to be a peristent inconsistency/error throughout the family of patents.
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58
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For example, in the sequence listing in the 13774718 parent application also shows this in the sequence listing for SEQ ID NO: 1 and its supposed encoded amino acid sequence.
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96
528
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Again, “ACC” does not encode Tyr, it encodes Thr.
Instant SEQ ID NO: 1 supposedly encodes instant SEQ ID NO: 2, but there is Tyr at instant amino acid 303 (throughout the entire patent family for SEQ ID NO: 2) and not a Thr.
Nonetheless, even with a Tyr at position 303 instead of Thr, the encoded amino acid sequence of the instant claims has 99.8% sequence identity with SEQ ID NO: 2 of the ‘599 patent.
Finally, with regard to a NLS as in claim 34, while the patented claims do not recite said NLS, it is clear when construing the scope of the patented claims in understanding a hyperactive piggybac transposase and as defined in the specification (See MPEP 804(II)(B)(1)), NLS sequences are clearly envisaged – See Col. 28, lines 10-38).
Claims 33-34 and 41-42 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10131885. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims to the 885’ patent render obvious the instant claims.
The instant claims in their broadest are drawn to: a hyperactive transposase protein comprising an amino acid sequence having at least 90% amino acid sequence identity to the protein encoded by the nucleotide sequence of SEQ ID NO: 1 and comprising at least one of the following amino acid substitutions as compared to the protein encoded by the nucleotide sequence of SEQ ID NO: 1: an asparagine for the serine at position 3; a valine for the isoleucine at position 30; a serine for the alanine at position 46; a threonine for the alanine at position 46; a tryptophan for the isoleucine at position 82; a proline for the serine at position 103; a pro line for the arginine at position 119; an alanine for the cysteine at position 125; a leucine for the cysteine at position 125; a serine for the glycine at position 165; a lysine for the tyrosine at position 177; a histidine for the tyrosine at position 177; a leucine for the phenylalanine at position 180; an isoleucine for the phenylalanine at position 180; a valine for the phenylalanine at position 180; a leucine for the methionine at position 185; a glycine for the alanine at position 187; a tryptophan for the phenylalanine at position 200; a proline for the valine at position 207; a phenylalanine for the valine at position 209; a phenylalanine for the methionine at position 226; an arginine for the leucine at position 235; a lysine for the valine at position 240; a leucine for the phenylalanine at position 241; a lysine for the pro line at position 243; a serine for the asparagine at position 258; a glutamine for the methionine at position 282; a tryptophan for the leucine at position 296; a tyrosine for the leucine at position 296; a phenylalanine for the leucine at position 296; a leucine for the methionine at position 298; an alanine for the methionine at position 298; a valine for the methionine at position 298; an isoleucine for the proline at position 311; a valine for the proline at position 311; a lysine for the arginine at position 315; a glycine for the threonine at position 319; an arginine for the tyrosine at position 327; a valine for the tyrosine at position 328; a glycine for the cysteine at position 340; a leucine for the cysteine at position 340; a histidine for the aspartic acid at position 421; an isoleucine for the valine at position 436; a tyrosine for the methionine at position 456; a phenylalanine for the leucine at position 470; a lysine for the serine at position 486; a leucine for the methionine at position 503; an isoleucine for the methionine at position 503; a lysine for the valine at position 552; a threonine for the alanine at position 570; a proline for the glutamine at position 591; or an arginine for the glutamine at position 591. Dependent claim 41 recites the hyperactive piggybac transposase of claim 33, comprises an amino acid substitution at positions 30, 165, 282, wherein the substitution at position 30 is a substitution of a Valine for an Isoleucine (I30V), and wherein the substitution at position 165 is a substitution of a Serine for a Glycine (G165S). Dependent claim 42 recites the hyperactive piggbac transposase of claim 41, wherein the substitution at position 282 is a substitution of any amino acid (X) for a Methionine (M282X), the amino acid (X) selected from the group consisting of a Leucine (L), an Isoleucine (I), a Valine (V), and an Alanine (A).
The claims to the ‘885 patent in their broadest are drawn to hyperactive transposase protein comprising at least 90% sequence identity to SEQ ID NO: 2, and comprising an amino acid substitution at positions 30, 165 and 282,
wherein the substitution at position 30 is a substitution of a Valine for an Isoleucine (I30V),
wherein the substitution at position 165 is a substitution of a Serine for a Glycine (G165S),
wherein the substitution at position 282 is a substitution of an amino acid (X) for a Methionine (M282X), the amino acid (X) selected from the group consisting of a Leucine (L), an Isoleucine (I), a Valine (V), and an Alanine (A), and wherein the hyperactive transposase protein is capable of mediating transposon integration at a higher frequency when compared to a wild type transposase having the sequence of SEQ ID NO: 2
Thus the difference between the ‘885 patent claims and the instant patent claims is the nucleic acid encoding the hyperactive piggybac transposase is not defined. However, the claims are not drawn to nucleic acids and therefore not limited by SEQ ID NO: 1, rather they are drawn to and limited to the encoded hyperactive transposase protein comprising SEQ ID NO: 2 or sequences having 90% identity thereto along with the requisite substitutions. Thus, claims 1 and 2 of the ‘559 would render obvious the instant claims when claims 33, 41 and 42 are combined.
It is noted, instant SEQ ID NO: 1 encodes a protein having 99.8% sequence identity to SEQ ID NO: 2 of the ‘885 patent, there being a single mismatch at amino acid 303 - See Supplemental Content, file 20260122_085950_us-18-051-109a-1.rai, Duplicates for Result #6, there being a Tyr at this position. In SEQ ID NO: 2, position 303 is a Tyr. It is noted, however, the codon “ACC” does not encode Tyr, instead it encodes Thr. This seems to be a peristent inconsistency/error throughout the family of patents.
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For example, in the sequence listing in the 13774718 parent application also shows this in the sequence listing for SEQ ID NO: 1 and its supposed encoded amino acid sequence.
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Again, “ACC” does not encode Tyr, it encodes Thr.
Instant SEQ ID NO: 1 supposedly encodes instant SEQ ID NO: 2, but there is Tyr at instant amino acid 303 (throughout the entire patent family for SEQ ID NO: 2) and not a Thr.
Nonetheless, even with a Tyr at position 303 instead of Thr, the encoded amino acid sequence of the instant claims has 99.8% sequence identity with SEQ ID NO: 2 of the ‘885 patent.
Finally, with regard to a NLS as in claim 34, while the patented claims do not recite said NLS, it is clear when construing the scope of the patented claims in understanding a hyperactive piggybac transposase and as defined in the specification (See MPEP 804(II)(B)(1)), NLS sequences are clearly envisaged – See Col. 28, lines 28-56).
Claims 33-34 and 41-42 area rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11485959. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims to the ‘959 patent render obvious the instant claims.
The instant claims in their broadest are drawn to: a hyperactive transposase protein comprising an amino acid sequence having at least 90% amino acid sequence identity to the protein encoded by the nucleotide sequence of SEQ ID NO: 1 and comprising at least one of the following amino acid substitutions as compared to the protein encoded by the nucleotide sequence of SEQ ID NO: 1: an asparagine for the serine at position 3; a valine for the isoleucine at position 30; a serine for the alanine at position 46; a threonine for the alanine at position 46; a tryptophan for the isoleucine at position 82; a proline for the serine at position 103; a pro line for the arginine at position 119; an alanine for the cysteine at position 125; a leucine for the cysteine at position 125; a serine for the glycine at position 165; a lysine for the tyrosine at position 177; a histidine for the tyrosine at position 177; a leucine for the phenylalanine at position 180; an isoleucine for the phenylalanine at position 180; a valine for the phenylalanine at position 180; a leucine for the methionine at position 185; a glycine for the alanine at position 187; a tryptophan for the phenylalanine at position 200; a proline for the valine at position 207; a phenylalanine for the valine at position 209; a phenylalanine for the methionine at position 226; an arginine for the leucine at position 235; a lysine for the valine at position 240; a leucine for the phenylalanine at position 241; a lysine for the pro line at position 243; a serine for the asparagine at position 258; a glutamine for the methionine at position 282; a tryptophan for the leucine at position 296; a tyrosine for the leucine at position 296; a phenylalanine for the leucine at position 296; a leucine for the methionine at position 298; an alanine for the methionine at position 298; a valine for the methionine at position 298; an isoleucine for the proline at position 311; a valine for the proline at position 311; a lysine for the arginine at position 315; a glycine for the threonine at position 319; an arginine for the tyrosine at position 327; a valine for the tyrosine at position 328; a glycine for the cysteine at position 340; a leucine for the cysteine at position 340; a histidine for the aspartic acid at position 421; an isoleucine for the valine at position 436; a tyrosine for the methionine at position 456; a phenylalanine for the leucine at position 470; a lysine for the serine at position 486; a leucine for the methionine at position 503; an isoleucine for the methionine at position 503; a lysine for the valine at position 552; a threonine for the alanine at position 570; a proline for the glutamine at position 591; or an arginine for the glutamine at position 591. Dependent claim 41 recites the hyperactive piggybac transposase of claim 33, comprises an amino acid substitution at positions 30, 165, 282, wherein the substitution at position 30 is a substitution of a Valine for an Isoleucine (I30V), and wherein the substitution at position 165 is a substitution of a Serine for a Glycine (G165S). Dependent claim 42 recites the hyperactive piggbac transposase of claim 41, wherein the substitution at position 282 is a substitution of any amino acid (X) for a Methionine (M282X), the amino acid (X) selected from the group consisting of a Leucine (L), an Isoleucine (I), a Valine (V), and an Alanine (A).
The claims to the ‘959 patent in their broadest are drawn to a hyperactive transposase protein comprising at least 90% sequence identity to SEQ ID NO: 2, and comprising an amino acid substitution at position 226, wherein the substitution at position 226 is a Phenylalanine for a Methionine (M226F), and wherein the hyperactive transposase protein is capable of mediating transposon integration at a higher frequency when compared to a wild type transposase having the sequence of SEQ ID NO: 2. Dependent claim 6 recites the hyperactive transposase protein further comprises an amino acid substitution at positions 30, 165 and 282, wherein the substitution at position 30 is a substitution of a Valine for an Isoleucine (I30V), wherein the substitution at position 165 is a substitution of a Serine for a Glycine (G165S), wherein the substitution at position 282 is a substitution of any amino acid (X) for a Methionine (M282X), the amino acid (X) selected from the group consisting of a Leucine (L), an Isoleucine (I), a Valine (V), and an Alanine (A). Dependent claims 7 and 8 recite nucleic acids encoding the hyperactive piggybac transposases of claims 1 and 6.
Thus, the single or quadruple substitutions all defined in the claims of the ‘959 patent are all claimed in the instant claims 33, 41 and 42. The difference between the ‘959 patent claims and the instant patent claims is the nucleic acid encoding the hyperactive piggybac transposase is not defined. However, the claims are not drawn to nucleic acids and therefore not limited by SEQ ID NO: 1, rather they are drawn to and limited to the encoded hyperactive transposase protein comprising SEQ ID NO: 2 or sequences having 90% identity thereto along with the requisite substitutions. Thus, claims 1 and 6-8 of the ‘959 would render obvious the instant claims when claims 33, 41 and 42 are combined.
It is noted, instant SEQ ID NO: 1 encodes a protein having 99.8% sequence identity to SEQ ID NO: 2 of the ‘959 patent, there being a single mismatch at amino acid 303 - See Supplemental Content, file 20260122_085950_us-18-051-109a-1.rai, Duplicates for Result #6, there being a Tyr at this position. In SEQ ID NO: 2, position 303 is a Tyr. It is noted, however, the codon “ACC” does not encode Tyr, instead it encodes Thr. This seems to be a peristent inconsistency/error throughout the family of patents.
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For example, in the sequence listing in the 13774718 great-grand parent application also shows this in the sequence listing for SEQ ID NO: 1 and its supposed encoded amino acid sequence.
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96
528
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Greyscale
Again, “ACC” does not encode Tyr, it encodes Thr.
Instant SEQ ID NO: 1 supposedly encodes instant SEQ ID NO: 2, but there is Tyr at instant amino acid 303 (throughout the entire patent family for SEQ ID NO: 2) and not a Thr.
Nonetheless, even with a Tyr at position 303 instead of Thr, the encoded amino acid sequence of the instant claims has 99.8% sequence identity with SEQ ID NO: 2 of the ‘959 patent.
Finally, with regard to a NLS as in claim 34, while the patented claims do not recite said NLS, it is clear when construing the scope of the patented claims in understanding a hyperactive piggybac transposase and as defined in the specification (See MPEP 804(II)(B)(1)), NLS sequences are clearly envisaged – See Col. 28, lines 33-61).
Claims 33-34 and 41-42 area rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4-10 of U.S. Patent No. 10329543. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims to the ‘959 patent render obvious/anticipate the instant claims.
The instant claims in their broadest are drawn to: a hyperactive transposase protein comprising an amino acid sequence having at least 90% amino acid sequence identity to the protein encoded by the nucleotide sequence of SEQ ID NO: 1 and comprising at least one of the following amino acid substitutions as compared to the protein encoded by the nucleotide sequence of SEQ ID NO: 1: an asparagine for the serine at position 3; a valine for the isoleucine at position 30; a serine for the alanine at position 46; a threonine for the alanine at position 46; a tryptophan for the isoleucine at position 82; a proline for the serine at position 103; a pro line for the arginine at position 119; an alanine for the cysteine at position 125; a leucine for the cysteine at position 125; a serine for the glycine at position 165; a lysine for the tyrosine at position 177; a histidine for the tyrosine at position 177; a leucine for the phenylalanine at position 180; an isoleucine for the phenylalanine at position 180; a valine for the phenylalanine at position 180; a leucine for the methionine at position 185; a glycine for the alanine at position 187; a tryptophan for the phenylalanine at position 200; a proline for the valine at position 207; a phenylalanine for the valine at position 209; a phenylalanine for the methionine at position 226; an arginine for the leucine at position 235; a lysine for the valine at position 240; a leucine for the phenylalanine at position 241; a lysine for the pro line at position 243; a serine for the asparagine at position 258; a glutamine for the methionine at position 282; a tryptophan for the leucine at position 296; a tyrosine for the leucine at position 296; a phenylalanine for the leucine at position 296; a leucine for the methionine at position 298; an alanine for the methionine at position 298; a valine for the methionine at position 298; an isoleucine for the proline at position 311; a valine for the proline at position 311; a lysine for the arginine at position 315; a glycine for the threonine at position 319; an arginine for the tyrosine at position 327; a valine for the tyrosine at position 328; a glycine for the cysteine at position 340; a leucine for the cysteine at position 340; a histidine for the aspartic acid at position 421; an isoleucine for the valine at position 436; a tyrosine for the methionine at position 456; a phenylalanine for the leucine at position 470; a lysine for the serine at position 486; a leucine for the methionine at position 503; an isoleucine for the methionine at position 503; a lysine for the valine at position 552; a threonine for the alanine at position 570; a proline for the glutamine at position 591; or an arginine for the glutamine at position 591. Dependent claim 41 recites the hyperactive piggybac transposase of claim 33, comprises an amino acid substitution at positions 30, 165, 282, wherein the substitution at position 30 is a substitution of a Valine for an Isoleucine (I30V), and wherein the substitution at position 165 is a substitution of a Serine for a Glycine (G165S). Dependent claim 42 recites the hyperactive piggbac transposase of claim 41, wherein the substitution at position 282 is a substitution of any amino acid (X) for a Methionine (M282X), the amino acid (X) selected from the group consisting of a Leucine (L), an Isoleucine (I), a Valine (V), and an Alanine (A).
The claims to the ‘543 patent in their broadest are drawn to methods of producing a plurality of expanded modified T cells (claim 1) by utilizing a transposase, specifically a hyperactive piggybac transposes comprising SEQ ID NO: 4 which has substitutions at positions 30, 165, 282 and 538 of SEQ ID NO: 4 (Dependent claims 4-7); specifically: an I30V substitution (Dependent claim 8); a G165S substitution (Dependent claim 9); a M282V substitution (Dependent claim 10); all of which are recited instant claims 33 and 41-42.
It is noted, instant SEQ ID NO: 2 and SEQ ID NO: 4 of the ‘543 patent have 100% sequence identity with one another – See Supplemental Content, file 20250827_112244_us-18-051-109a-2.minpct90.rai, Duplicates for Result #1.
Thus, the difference between the claims is the claims of the ‘543 patent are drawn to methods of using the same/overlapping hyperactive piggybac transposes which have the same substitutions as claimed in claims 33 and 41-42. An additional difference is the ‘543 patent claims does not define any nucleic acid encoding the hyperactive piggybac transposase. However, the claims are not drawn to nucleic acids and therefore not limited by SEQ ID NO: 1, rather they are drawn to and limited to the encoded hyperactive transposase protein comprising SEQ ID NO: 2 or sequences having 90% identity thereto along with the requisite substitutions. Thus, claims 1 and 6-8 of the ‘959 would render obvious the instant claims when claims 33, 41 and 42 are combined.
It is noted, instant SEQ ID NO: 1 encodes a protein having 99.8% sequence identity to SEQ ID NO: 4 of the ‘543 patent, there being a single mismatch at amino acid 303 - See Supplemental Content, file 20260122_085950_us-18-051-109a-1.rai, Duplicates for Result #6, there being a Tyr at this position. In SEQ ID NO: 2, position 303 is a Tyr. It is noted, however, the codon “ACC” does not encode Tyr, instead it encodes Thr. This seems to be a peristent inconsistency/error throughout the family of patents.
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Instant SEQ ID NO: 1 supposedly encodes instant SEQ ID NO: 2, but there is Tyr at instant amino acid 303 (throughout the entire patent family for SEQ ID NO: 2) and not a Thr.
Nonetheless, even with a Tyr at position 303 instead of Thr, the encoded amino acid sequence of the instant claims has 99.8% sequence identity with SEQ ID NO: 2 of the ‘543 patent.
Conclusion
No claim is allowed.
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 22 January 2026