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 .
DETAILED ACTION
Status of the Claims
Claims 1, 6-11, 13-15, 18-20, 23, 25, 32 and 33-37 are pending. Claims 1, 6-11, 13-15, 25, 32 and 34-37 are the subject of this NON-FINAL Office Action. Claims 18-20, 23 and 33 are withdrawn. This is the first action on the merits.
The prior art rejections are based on the Third-Party Submission 07/13/2023, with which the Examiner agrees. This also reflects the European Opposition filed 04/13/2023.
Election/Restrictions
Applicant’s election without traverse of the species of (1) polynucleotide “leader” (2) Dda helicase “polynucleotide-handling protein”, (3) conjugate of claim 15 and (4) adaptor attachment in the reply filed on 09/02/2025 is acknowledged. The elections read on claims 1, 6-11, 13-15, 25, 32 and 34-37.
Claims 18-20, 23 and 33 are withdrawn.
Claim Interpretations
As to “polynucleotide-handling protein capable of controlling the movement of the polynucleotide with respect to the nanopore,” this is any protein capable of “handling” a polynucleotide (e.g. polymerase, DNase, RNase, restriction enzyme, recombinase, etc.). Despite this intentional functional breadth on the part of Applicants, the only example disclosed in any detail is helicase (para. 0288). Thus, although the claims are interpreted to encompass any protein capable of interacting with a polynucleotide, yet the only detailed example is helicase. Applicants are strongly encouraged to amend the claims accordingly.
As to a “leader” intended to “facilitate[] the threading of the conjugate through the nanopore,” again the structure required is never defined, but is broadly interpreted as any nucleic acid sequence (see para. 0025- “L is a leader, wherein L is optionally an N moiety . . . N comprises a polynucleotide”), or polymer (e.g. PEG, polysaccharide, nylon, polyethylene, polypropylene, etc.; see para. 0221- “ In some embodiments the leader comprises a polymer”). Yet, the only specific example is disclosed in Example 1: “The Y adapter contains 30 C3 leader section for easier capture by the nanopore and a side arm for tethering to the membrane” (para. 0386). Once again, Applicants are strongly encouraged to amend the claims accordingly.
As to claims 6-8, the claimed functionality (“capable of”) of the “polynucleotide-handling protein” is never clearly tied to any particular structure in the specification; thus, claims 6-8 encompass any “polynucleotide-handling protein.” For example, the specification discloses that helicases perform these functions; thus, any prior art helicase meets the claimed functions.
As to “adaptors,” “tethers” and “anchors,” again no definition is provided; they encompass any polynucleotides.
Claim 25 merely recites an intended use of the measurements; thus, it does not further limit the method of claim 1. To the extent the claims are ever amended to recite detecting or determining the characteristics of claim 25, the Examiner agrees with the enablement assessment in related U.S. Application No. 18/357504 (polypeptide length, identity or modification are enabled; not sequence or secondary structure).
As should be clear from the above comments, the claims are much too broad to warrant allowable subject matter. Significant amendments are required.
Claim Rejections - 35 USC § 112- Indefiniteness
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.
Claims 1, 4-9 and 20 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 pre-AIA the applicant regards as the invention.
As explained above, as to “polynucleotide-handling protein capable of controlling the movement of the polynucleotide with respect to the nanopore,” this functional language is never clearly tied to any specific proteins. One example is disclosed (helicase), but this single example fails to suffice to define an entire genus of proteins. In other words, it is completely unclear what other proteins are encompassed by this purely functional phrasing.
This same analysis applies to claim 6-8, where the claims also state pure functionality of the claimed “polynucleotide-handling protein.” For example, claim 6 states “the polynucleotide-handling protein is capable of remaining bound to the conjugate when the portion of the conjugate in contact with the active site of the polynucleotide-handling protein comprises a polypeptide.” The specification simply never explains what specific structures yield this result. A skilled artisan is left to guess what among thousands of potential “proteins” allows these particular functions in this nanopore context.
Claim 36 contains an improper Markush grouping. All lists of alternative must be in Markush format, which requires a closed format. See MPEP §§ 2117 & 2173.05(h).
In addition, claim 36 recites “preferably, which is confusing. See MPEP § 2173.05(d).
Finally, claim 36 recites that the “transmembrane protein pore [is] . . . based on” various known pore proteins. It is entirely unclear how the pore protein is “based on” another protein because “based on” is inherently vague.
Claim Rejections - 35 USC § 102
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 –
(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.
Claims 1, 6-9, 11, 13, 25, 32 and 34-37 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by BAI (US20220365094).
As to claim 1, BAI teaches characterizing polypeptide (pp) (para. 0020) by conjugating pp to polynucleotide (pn) (para. 0021); contacting the conjugate with a polynucleotide-handling protein capable of controlling the movement of the polynucleotide with respect to a nanopore (paras. 0022-23); and taking one or more measurements characteristic of the polypeptide as the conjugate moves with respect to the nanopore, thereby characterising the polypeptide (para. 0024), wherein the conjugate comprises a leader that facilitates the threading of the conjugate through the nanopore (para. 0085 and Fig. 2).
As to claims 6-9, BAI teaches helicase (para. 0006).
As to claim 11, BAI teaches polypeptide 2-50 amino acids (para. 0098).
As to claim 13, BAI teaches polynucleotide 10-1000 nucleotides (id.)
As to claim 25, BAI teaches the one or more measurements are characteristic of one or more characteristics of the polypeptide selected from (i) the length of the polypeptide, (ii) the identity of the polypeptide, (iii) the sequence of the polypeptide, (iv) the secondary structure of the polypeptide and (v) whether or not the polypeptide is modified (para. 0007).
As to claim 32, BAI teaches leader pn or polymer (para. 0084 and Fig. 1).
As to claim 34, BAI teaches ion flow current measured (para. 0020).
As to claims 35-36, BAI teaches pore protein is MspA (para. 0019).
As to claim 37, BAI teaches constriction region (paras. 0110 & 0114).
Claims 1, 10, 32 and 34 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by BAYLEY (WO2015040423).
As to claim 1, BAYLEY teaches characterizing polypeptide (pp) (pg. 7, ll. 18-25) by conjugating pp to polynucleotide (pn) (pg. 10, ll. 31-33); contacting the conjugate with a polynucleotide-handling protein capable of controlling the movement of the polynucleotide with respect to a nanopore (pg. 10, ll. 29-31); and taking one or more measurements characteristic of the polypeptide as the conjugate moves with respect to the nanopore, thereby characterising the polypeptide (pg. 7, ll. 22-24), wherein the conjugate comprises a leader that facilitates the threading of the conjugate through the nanopore (pg. 10, ll. 28-29).
As to claim 10, BAYLEY teaches plurality of and/or polynucleotide (pg. 10, ll. 26-29).
As to claim 32, BAYLEY teaches leader pn or polymer (pg. 10, ll. 28-29; pg. 35, ll. 4-8; Fig. 1).
As to claim 34, BAYLEY teaches ion flow current measured (pg. 7, ll. 22-24; pg. 32, ll. 15-18).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 6-11, 13-15, 25, 32 and 34-37 is/are rejected under 35 U.S.C. 103 as being unpatentable over BAI and BAYLEY, in view of HERON (WO2014013260) and JAYASINGHE (WO2017149317).
The prior art as a whole demonstrates that it would have been obvious to a skilled artisan at the time of filing to apply familiar nanopore modulating techniques to the nanopore modulation of BAI and BAYLEY with a reasonable expectation of success.
As explained above, BAI and BAYLEY teach to measure and detect polypeptide sequences and structures in nanopores using modulated movement in the nanopore. Their methods include the use of helicase to do so. Neither BAI nor BAYLEY explicitly teach adaptors, tethers and/or anchors (claim 14); or cis-trans configuration of helicase and conjugate (claim 15).
However, these were known techniques to further control movement through a nanopore. For example, HERON teaches helicases such as Dda helicases to perform the functions of claims 6-8, and further control movement through the nanopore (pgs. 1, 18 & 23). To this similar end, JAYASINGHE teaches helicase combined with double-stranded Y-adaptors, anchors and tethers to allow further control of movement through a nanopore, including cis helicase and conjugate moved from cis to trans (pg. 64, ll. 1-2; pg. 82, ll. 12-13; pg. 92, ll. 6-8; pg. 94, l. 17 – pg. 95, l. 3; pg. 66, ll. 5-6; pg. 66, ll. 19-29).
In sum, the claims are directed to the combination of familiar nanopore control elements to achieve familiar results, rendering the claims obvious.
Double Patenting- Obvious Type
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Instant claims 1, 6-11, 13-15, 25, 32 and 34-37are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1, 9-11, 15, 18-20, 23 and 32-38 of 18/357504.
The instant claims are obvious over the conflicting claims because the conflicting claims teach a species of the instant claims. More specifically, the conflicting claims teach:
1. A method, comprising
(i) conjugating a target polypeptide to a polynucleotide to form a polynucleotide- polypeptide conjugate;
(ii) contacting the conjugate with a polynucleotide-handling protein;
(ii) controlling movement of the polynucleotide with respect to a transmembrane protein pore using the polynucleotide-handling protein; and
(iv) taking one or more measurements characteristic of the polypeptide as the conjugate moves with respect to the transmembrane protein pore;
wherein the one or more measurements are indicative of one or more characteristics of the polypeptide selected from: (a) the length of the polypeptide, (b) the identity of the polypeptide, and (c) whether or not the polypeptide comprises post-translational modification,
wherein the conjugate comprises a leader that facilitates threading of the conjugate through the transmembrane protein pore, and wherein the transmembrane protein pore comprises a cis side and a trans side.
It is clear from the face of conflicting claim 1, and dependent claims, that the conflicting claims anticipate the instant claims.
Conclusion
No claims are allowed.
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/AARON A PRIEST/Primary Examiner, Art Unit 1681