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 .
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 114 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 114 recites the limitation "the purification tag" in line 2. There is insufficient antecedent basis for this limitation in the claim. There is no claim limitation that provides for a literal antecedent basis nor a reasonable inherent antecedent basis for “the purification tag” such that it is unclear what claim feature is referenced.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 104, 107, 113-116, and 118-123 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Reed et al. (U.S. 2018/0208911 A1) (see IDS, 06/03/24).
Reed, abstract, states:
Compositions comprising modified recombinant polymerizing enzymes are provided, along with nucleic acid molecules encoding the modified polymerizing enzymes. In some aspects, methods of using such polymerizing enzymes to synthesize a nucleic acid molecule or to sequence a nucleic acid template are provided.
Compositions comprising modified recombinant polymerizing enzymes are provided, along with nucleic acid molecules encoding the modified polymerizing enzymes. In some aspects, methods of using such polymerizing enzymes to synthesize a nucleic acid molecule or to sequence a nucleic acid template are provided.
“In some aspects, the disclosure provides a modified polymerizing enzyme (e.g., a nucleic acid polymerizing enzyme, or a nucleic acid polymerase) having an amino acid sequence that is based on a naturally occurring polymerase (e.g., selected from Table 1) and that includes one or more amino acid mutations and/or segment substitutions.” Reed, para. [0005].
“In some embodiments, a modified polymerase sequence comprises a majority sequence further comprising one or more amino acid mutations. In some embodiments, one or more amino acid mutations comprise amino acids at positions corresponding to positions in homologous proteins. For example, in some embodiments, a modified polymerase comprises a mutation at a position corresponding to A484 in Φ29 polymerase (SEQ ID NO: 1). An amino acid corresponding to A484 in other polymerases can be determined by any method known in the art, including homology alignment. As a non-limiting example of this analysis, a homology alignment was conducted with a number of the polymerases reported in Table 1, and it was determined that A484 in Φ29 polymerase corresponds to A481 in M2Y, A492 in Bacillus phage VMY22, K500 in Enterococcus faecium, and K827 in Lucilia cuprina.” Reed, para. [0043].
Enterococcus faecium polymerase is SEQ ID NO: 5 as shown in Table 1 of Reed. SEQ ID NO: 5 of Reed is over 99% identical to recited SEQ ID NO: 2 as shown in the following alignment:
PNG
media_image1.png
448
760
media_image1.png
Greyscale
PNG
media_image2.png
361
742
media_image2.png
Greyscale
“In some embodiments, a modified polymerase has at least 25% amino acid sequence identity to one or more of the polymerases listed in Table 1 (e.g., to SEQ ID NO: 1, SEQ ID NO: 5, or other sequence listed in Table 1). In some embodiments, a modified polymerase has 25-50%, 50-60%, 60-70%, 70-80%, 80-90%, 90-95%, or 95-99%, or higher amino acid sequence identity to one or more of the polymerases listed in Table 1 (e.g., to SEQ ID NO: 1, SEQ ID NO: 5, or other sequence listed in Table 1).” Reed, para. [0044].
The above is considered to be an anticipatory disclosure of a modified DNA polymerase having at least 95% or 99% identity to recited SEQ ID NO: 2, where modification is a substitution of K500 as to anticipate all of the features of claims 104 and 107.
Regarding claims 113-116 and 118-119, the following disclosure of Reed is noted:
“In some embodiments, a recombinant polymerizing enzyme further comprises a purification tag. In some embodiments, the purification tag is covalently bound to a region within the polymerizing enzyme sequence. In some embodiments, the purification tag is covalently bound at a terminal end of the polymerizing enzyme sequence. In some embodiments, the purification tag is a C-terminal tag. In some embodiments, the purification tag is an N-terminal tag. In some embodiments, the purification tag is a His tag (e.g., a sequence of repeating histidine residues, such as a hexahistidine sequence).” Reed, para. [0008]. “In some embodiments, a recombinant polymerizing enzyme further comprises a coupling group. In some embodiments, the coupling group is attached at a region within the polymerizing enzyme sequence. In some embodiments, the coupling group is attached at a terminal end of the polymerizing enzyme. In some embodiments, the coupling group is attached at a C-terminal end of the recombinant polymerizing enzyme. In some embodiments, the coupling group is attached at an N-terminal end of the recombinant polymerizing enzyme. In some embodiments, the coupling group is a biotinylation sequence.” Reed, para. [0009].
“In some embodiments, a recombinant polymerizing enzyme is immobilized on a surface. In some embodiments, the surface comprises a coupling group configured to bind the recombinant polymerizing enzyme. In some embodiments, the surface comprises a nanoaperture.” Reed, para. [0010].
As such, Reed is considered to disclose in an anticipatory manner that any modified DNA polymerase consistent with the disclosure of Reed can have the features of claims 113-116 and/or immobilized on a surface with a nanoaperture as recited in claims 118-119.
Regarding claims 120-121, the abstract of Reed indicates that any DNA polymerase disclosed by Reed can be in a composition and/or encoded by an nucleic acid sequence. “In some aspects, the disclosure provides an isolated nucleic acid molecule that encodes a recombinant polymerizing enzyme described herein.” Reed, para. [0011].
Regarding claims 122-123, “In some aspects, the disclosure provides a composition comprising a recombinant polymerizing enzyme described in this application. In some embodiments, the composition is used in a method of sequencing a nucleic acid. In some embodiments, the composition further comprises a sequencing reaction mixture. In some embodiments, the sequencing reaction mixture can include one or more of a nucleoside polyphosphate (e.g., a nucleoside comprising more than one phosphate group, such as a nucleotide or a nucleoside hexaphosphate), a template nucleic acid to be sequenced, a nucleic acid primer that serves as a starting point for complementary strand synthesis, a divalent metal ion, a buffer component, and a salt.” Reed, para. [0012]. “In some aspects, the disclosure provides a method of sequencing a nucleic acid by contacting a recombinant polymerizing enzyme described in this application with a sequencing reaction mixture. In some embodiments, the sequencing reaction mixture can include one or more of a nucleoside polyphosphate (e.g., a nucleoside comprising more than one phosphate group, such as a nucleotide or a nucleoside hexaphosphate), a template nucleic acid to be sequenced, a nucleic acid primer that serves as a starting point for complementary strand synthesis, a divalent metal ion, a buffer component, and a salt.” Reed, para. [0013]. As such, Reed discloses that any modified DNA polymerase as taught therein be employed for a method of sequencing as recited in claims 122-123.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 104, 106, 107, 113-116, and 118-123 is/are rejected under 35 U.S.C. 103 as being unpatentable over Reed et al. (U.S. 2018/0208911 A1).
The rejections of claims 104, 107, 113-116, and 118-123 as anticipated by Reed set forth above are incorporated herein by reference.
Regarding claim 106, as discussed above, Reed directly states modification of K500 in SEQ ID NO: 5 of Reed that corresponds to A484 in Φ29 polymerase (SEQ ID NO: 1). “In some embodiments, a modified polymerase comprises mutations at one or more positions (e.g., at 1-18 positions or any whole number in between, for example 2 or more, 5 or more, 10 or more, 15 or more, for example all) corresponding to K135, L142, Y224, E239, V250, L253, E375, A437, E466, D476, A484, E508, D510, K512, E515, K539, D570, and T571 in Φ29 polymerase. In some embodiments, a modified polymerase of the disclosure is a modified Φ29 polymerase comprising mutations at one or more of K135, L142, Y224, E239, V250, L253, E375, A437, E466, D476, A484, E508, D510, K512, E515, K539, D570, and T571. In some embodiments, the modified polymerase comprises one or more (e.g., 1-18 or any whole number in between, for example 2 or more, 5 or more, 10 or more, 15 or more, for example all) of K135Q, L142K, Y224K, E239G, V250I, L253A, E375Y, A437G, E466K, D476H, A484E, E508R, D510R, K512Y, E515Q, K539E, D570S, and T571V.” Reed, para. [0052].
Reed does not directly state that the substitution of K500 in SEQ ID NO: 5 of Reed be to Glu(E). However, in order to produce an embodiment of SEQ ID NO: 5 of Reed with substitution of K500 substitution to some other amino acid residue must be made. Since Reed directly teaches that K500 of SEQ ID NO: 5 of Reed corresponds to A484 of Reed, in performing a substitution of K500 of SEQ ID NO: 5 as discussed by Reed an ordinarily skilled artisan at the time of filing would have been motivated to utilize the same substitution as to SEQ ID NO: 1 of Reed, which is substitution to Glu(E). An ordinarily skilled artisan at the time of filing would have motivated to do the same since Reed expressly teaches that substitution to Glu(E) is a preferred substitution of a position corresponding to A484 of SEQ ID NO: 1 of Reed and by extension the substitution K500E in SEQ ID NO: 5 of Reed.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claim 112 and 117 is/are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 9 and 17 of prior U.S. Patent No. 11,959,105. This is a statutory double patenting rejection.
“A reliable test for double patenting under 35 U.S.C. 101 is whether a claim in the application could be literally infringed without literally infringing a corresponding claim in the patent.” MPEP 804(II)(A). Statutory double patenting therefore does not require claims to be completely verbally identical.
Patented claim 9 recites: The modified recombinant DNA polymerase of claim 8, wherein the modified recombinant DNA polymerase comprises the amino acid sequence of SEQ ID NO: 157.
Claim 112 recites: The modified recombinant DNA polymerase of claim 104, wherein the modified recombinant DNA polymerase comprises the amino acid sequence of SEQ ID NO: 157.
While patented claim 9 and claim 112 depend from claims with different scopes, patented claim 9 and claim 112 narrow the scope to DNA polymerases comprising the amino acid sequence of SEQ ID NO: 157 wherein there is no apparent way to infringe patented claim 9 without infringing claim 112, and vice versa.
Similarly, patented claim 11 and claim 117 are identical after the transitional phrase and appear to have the same scope. It is noted claim 117 depends from claim 116 reciting presence of a coupling group being a biotinylation sequence, while patented claim 11 depends from claim 10 reciting a bis-biotin tag. The specification gives SEQ ID NO: 843 as an example of a biotinylation sequence and gives SEQ ID NO: 844 as a bis-biotinylation sequence. All 27 amino acid residues of SEQ ID NO: 843 are identical to positions 2-28 of SEQ ID NO: 844. An alignment between SEQ ID NO: 180 and SEQ ID NO: 844 is as follows:
PNG
media_image3.png
162
590
media_image3.png
Greyscale
As such, SEQ ID NO: 180 as recited in patented claim 11 and claim 117 comprises a biotinylation sequence and a bis-biotinylation sequence such that the scope of patented claim 11 and claim 117 are the same regardless of depending from claims with different scope. Stated in other words, there is no apparent way to infringe patented claim 11 without infringing claim 117, and vice versa.
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 104-112 and 115-117 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,959,105 B2. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Patented claims recite:
1. A modified recombinant DNA polymerase based on SEQ ID NO: 2, comprising a first segment and a second segment, wherein:
the first segment consists of an amino acid sequence corresponding to a first reference segment, said first reference segment consisting of amino acids 197-271 of SEQ ID NO: 2, wherein the amino acid sequence of the first segment is at least 80%, 80-90%, 90-95%, or at least 95% identical to the amino acid sequence of the first reference segment, and wherein the first segment has a higher isoelectric point than the first reference segment; and
the second segment consists of an amino acid sequence corresponding to a second reference segment, said second reference segment consisting of amino acids 443-528 of SEQ ID NO: 2, wherein the amino acid sequence of the second segment is at least 80%, 80-90%, 90-95%, or at least 95% identical to the amino acid sequence of the second reference segment, and wherein the second segment has a higher isoelectric point than the second reference segment.
7. The modified recombinant DNA polymerase of claim 6, wherein the modified recombinant enzyme comprises the amino acid sequence of SEQ ID NO: 88.
9. The modified recombinant DNA polymerase of claim 8, wherein the modified recombinant DNA polymerase comprises the amino acid sequence of SEQ ID NO: 157.
11. The modified recombinant DNA polymerase of claim 10, wherein the modified recombinant DNA polymerase comprises the amino acid sequence of SEQ ID NO: 180.
An alignment between SEQ ID NO: 2 and SEQ ID NO: 180 is below wherein SEQ ID NO: 180 embodies a modified recombinant DNA polymerase having over 95% identity to SEQ ID NO: 2 embodying substitutions E60L, L264H, V261A, K500E, R308G, and others and has a biotinylation sequence coupling group at the C-terminus as recited in claims 115-117.
PNG
media_image4.png
504
653
media_image4.png
Greyscale
PNG
media_image5.png
273
641
media_image5.png
Greyscale
SEQ ID NO: 157 has over 95% identity to SEQ ID NO: 2 with at least substitutions E60L, L264H, V261A, K500E, R308G, I148K, E391Y, E523K, E482K, D492H, E142K, E537K and K521K, as recited in claims 108, 109 and 110.
Claims 104-123 (all pending claims) are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,959,105 B2 in view of Rothberg et al. (WO 2018/118997 A2).
The rejection of claims 104-112 and 115-117 on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,959,105 B2 stated above is incorporated herein by reference.
Regarding claims 113 and 114, Rothberg, abstract, teaches Compositions comprising modified recombinant polymerizing enzymes are provided, along with nucleic acid molecules encoding the modified polymerizing enzymes. SEQ ID NO: 31 of Rothberg (see Table 2) is identical to recited SEQ ID NO: 2. “In some embodiments, a recombinant polymerizing enzyme further comprises a purification tag. In some embodiments, the purification tag is covalently bound to a region within the polymerizing enzyme sequence. In some embodiments, the purification tag is covalently bound at a terminal end of the polymerizing enzyme sequence. In some embodiments, the purification tag is a C-terminal tag. In some embodiments, the purification tag is an N-terminal tag. In some embodiments, the purification tag is a His tag. Rothberg, para. [0008]. As such, Rothberg teaches that is well established to include a Histidine purification tag fused to a DNA polymerase. As such, at the time of filing an ordinarily skilled artisan would have been motivated to fuse a histidine purification tag to any of the specific recombinant modified DNA polymerases recited in the patented claims including those having SEQ ID NO: 157 or 180.
Regarding claims 118 and 119, “In some embodiments, a recombinant polymerizing enzyme is immobilized on a surface. In some embodiments, the surface comprises a coupling group configured to bind the recombinant polymerizing enzyme. In some embodiments, the surface comprises a nanoaperture.” Rothberg, para. [0010]. As such, it is established in the prior art to immobilize a DNA polymerase on a surface with a nanoaperture such that at the time of filing an ordinarily skilled artisan would have been motivated to do the same immobilization with any of the specific recombinant modified DNA polymerases recited in the patented claims including those having SEQ ID NO: 157 or 180.
Regarding claim 120, Rothberg, abstract, teaches that it is appropriate for a DNA polymerase to be encoded by a nucleic acid and an ordinarily skilled artisan at the time of filing would have recognized that expression from a nucleic acid is a principal way for producing “recombinant” DNA polymerases. See Rothberg, para. [0089]. As such, at an the time of filing an ordinarily skilled artisan would have been motivated to encode any of the specific recombinant modified DNA polymerases recited in the patented claims including those having SEQ ID NO: 157 or 180 in a nucleic acid for the purpose of producing the same DNA polymerases.
Regarding claim 121, Rothberg teaches that it is appropriate to include a DNA polymerase in a composition such that at the time of filing an ordinarily skilled artisan would have been motivated to do the same including any of the DNA polymerases of the patented claims.
Regarding claim 122-123, “In some aspects, the disclosure provides a method of sequencing a nucleic acid by contacting a recombinant polymerizing enzyme described in this application with a sequencing reaction mixture. In some embodiments, the sequencing reaction mixture can include one or more of a nucleoside polyphosphate (e.g., a nucleoside comprising more than one phosphate group, such as a nucleotide or a nucleoside hexaphosphate), a template nucleic acid to be sequenced, a nucleic acid primer that serves as a starting point for complementary strand synthesis, a divalent metal ion, a buffer component, and a salt.” Rothberg, para. [0013]. As such, Rothberg teaches that applying a DNA polymerase to a method of sequencing as recited in claims 122-123 is a known application for DNA polymerases such that at the time of filing an ordinarily skilled artisan would have been motivated to apply any of the specific DNA polymerases recited in the patented claims to such sequencing methods.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TODD M EPSTEIN whose telephone number is (571)272-5141. The examiner can normally be reached Mon-Fri 9:00a-5:30p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TODD M EPSTEIN/Primary Examiner, Art Unit 1652