DETAILED ACTION
Reassignment of the Application
1. Please note that this application has been reassigned to Examiner Kaijiang Zhang, in Art Unit 1684. In order to expedite accurate processing of the application papers, all future correspondence with the Office should reflect this change.
Notice of Pre-AIA or AIA Status
2. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
3. Applicant’s election without traverse of Group I (claims 1-7) in the reply filed on 8/14/2025 is acknowledged.
4. Claims 1-15 are pending in the application. Claims 8-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-7 are currently under examination.
Claim Rejections - 35 USC § 112
5. 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.
6. Claim 6 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 6, dependent from claim 5 which depends from claim 4 which further depends from claim 1, recites “wherein the molar ratio of lipid to MSP to nanopore protein is about 101:6:1 or about 120:6:1” (emphasis provided). Since claim 1 recites a “first lipid” and a “second lipid” (and claim 5 further defines the “first lipid” and the “second lipid”), it is unclear whether the “lipid” recited in claim 6 refers to the “first lipid”, the “second lipid”, or both the “first lipid” and the “second lipid”.
For purposes of current examination, the “lipid” recited in claim 6 is being interpreted as referring to the “first lipid” because the “aqueous mixture” recited in step (a) of the claimed method comprises the “first lipid” but not the “second lipid”.
Claim Rejections - 35 USC § 103
7. 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 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.
8. 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 of this title, 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.
9. 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.
10. Claims 1-3 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Boyanov et al. (US 2017/0260582 A1) in view of Ivanov et al. (US 2018/0230531 A1).
Regarding claim 1
Boyanov et al. teach, throughout the whole document, a method of making a detection apparatus (see paragraph [0076]: “This disclosure further provides a method of making a detection apparatus…”) comprising one or more native nanopore proteins (see paragraph [0042]: “…a hybrid nanopore system based upon a solid-state nanopore sealed by a protein-pore embedded lipid nanodisc”), comprising the steps of: (a) forming an aqueous mixture comprising a nanopore protein, a membrane scaffold protein (MSP), and a first lipid to produce a sample of nanodisc-nanopore protein complexes (see paragraph [0044]: “Particular embodiments employ insertion of a protein nanopore into a lipid nanodisc carrier …… lipid bilayer disc that is optionally stabilized by membrane scaffold protein (MSP)”; paragraph [0010]: “…a protein nanopore is initially self-assembled within a lipid nanodisc in free solution”; paragraph [0075]: “…aqueous environment…”), wherein a population of the nanodisc-nanopore protein complexes in the sample each comprise a native nanopore protein (see paragraph [0076]: “…providing a plurality of lipid nanodiscs, wherein the lipid nanodiscs include protein nanopores inserted in the lipid”); (b) providing a solid support comprising one or more apertures (see paragraph [0076]: “…providing a solid support having an array of solid state nanopores”), wherein a membrane is formed over each of the apertures (see paragraph [0081]: “…a membrane surrounding the nanopore”; paragraph [0067]: “…a seal that is formed over a solid state nanopore prevents flow of fluids and/or flow of electrical current. However, a protein nanopore can form an aperture in the seal.”); and (c) contacting the one or more membranes with the population of nanopore-nanodisc complexes comprising the native nanopore protein to assimilate a native nanopore protein into each of the membranes (see paragraph [0117]: “…(a) engineer, synthesize and purify the protein-nanodisc complex; and (b) assemble the complex on the solid state nanopore platform by electrophoretic forces. The electrophoretic driving force can be enhanced by attaching polyelectrolyte or DNA molecule on the disc or pore-forming protein.”). Boyanov et al. do not specifically disclose wherein the membrane comprises a second lipid, and wherein the membrane separates a cis chamber from a trans chamber in the detection apparatus.
However, Ivanov et al., in the same field of apparatuses and methods for sequencing macromolecules (see paragraph [0002]), teach a membrane comprises a second lipid, and wherein the membrane separates a cis chamber from a trans chamber in the detection apparatus (see paragraph [0027]: “…a nanopore complex extending through a lipid bilayer. The lipid bilayer separates a first volume and a second volume of a measurement module. By convention a sequencing module comprises a first chamber, which can be referred as the cis chamber, and a second chamber, which can be referred to as the trans chamber, where the cis and trans chambers can be separated by a nanopore-containing bilayer membrane.”).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boyanov et al. with the teaching of Ivanov et al. for the purpose of improving device manufacturing quality to prevent poor signal to noise ratios and differences in the osmolality of the solutions on either side of the nanopore-containing membrane (see Ivanov et al., paragraph [0004]). In addition, combining prior art elements according to known methods to yield predictable results is considered prima facie obvious (see MPEP 2143.I.A). Given the teachings of the prior art and the level of the ordinary skilled artisan at the effective filing date of the claimed invention, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Regarding claim 2
The method of Boyanov et al. in view of Ivanov et al., further comprising the step of purifying the population of nanopore-nanodisc complexes comprising the native nanopore protein from the aqueous mixture prior to the step of contacting the one or more membranes with the population of nanopore-nanodisc complexes comprising the native nanopore protein (see Boyanov et al., paragraphs [0050] and [0117]).
Regarding claim 3
The method of Boyanov et al. in view of Ivanov et al., wherein the step of purifying the population of nanopore-nanodisc complexes comprising the native nanopore protein comprises one or both of size-exclusion chromatography and affinity chromatography (see Boyanov et al., paragraphs [0050] and [0117]).
Regarding claim 7
The method of Boyanov et al. in view of Ivanov et al., wherein the solid support comprises a plurality of apertures, wherein a membrane is formed over each of the plurality of apertures, and wherein each of the membranes is contacted with the nanopore-nanodisc complex comprising the native nanopore protein (see Boyanov et al., paragraphs [0067], [0076] and [0081]).
11. Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Boyanov et al. (US 2017/0260582 A1) in view of Ivanov et al. (US 2018/0230531 A1) as applied to claim 1 above, and further in view of Stangl et al. (Biophys. J. 2012, 103(12):2455-2464).
Boyanov et al. in view of Ivanov et al. teach the method of claim 1 as discussed above. Boyanov et al. further teach wherein the aqueous mixture further comprises a detergent (see paragraph [0046]: “Lipid nanodiscs can be prepared by mixing MSP with detergent stabilized phospholipid. Self-assembly of nanodiscs occurs during removal of the detergent from the mixture”; paragraph [0128]: “…neutral pH buffer, which is not expected to affect the stability of s lipid disc/biopore complex.”). Boyanov et al. do not explicitly disclose wherein the final concentration of the detergent is from about 14mM to about 40mM.
Stangl et al., in the field of detergent properties (see Title), teach that a final concentration of the detergent is from about 14mM to about 40mM (see page 2458, column 1, paragraph 1: “…a detergent concentration of 20 mM”).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boyanov et al. in view of Ivanov et al. with the teaching of Stangl et al. for the purpose of using a detergent concentration that will not cause membrane lysis (see Stangl et al., page 2462, column 1, paragraph 1). Given the teachings of the prior art and the level of the ordinary skilled artisan at the effective filing date of the claimed invention, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
12. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Boyanov et al. (US 2017/0260582 A1) in view of Ivanov et al. (US 2018/0230531 A1) and Stangl et al. (Biophys. J. 2012, 103(12):2455-2464) as applied to claim 4 above, and further in view of Holden et al. (WO 2017/004504 A1), Nasr et al. (WO 2018/213372 A1) and Sligar et al. (US 2009/0257950 A1).
Boyanov et al. in view of Ivanov et al. and Stangl et al. teach the method of claim 4 as discussed above. Boyanov et al. further teach the nanopore protein is α-hemolysin (α-HL) or a variant thereof (see paragraphs [0046] and [0062]). Boyanov et al. do not explicitly disclose wherein the first lipid is 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC), the MSP is MSP1D1 or a variant thereof, the detergent is cholate, and the second lipid is 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhPE).
Holden et al., in the field of lipid bilayer membrane compositions (see Abstract), teach a first lipid is 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC), and a second lipid is 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhPE) (see paragraph [0084]: “…the lipid in the lipid-polymer solution can include 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC), 1,2-diphytanoyl-sn-glycero-3-phosphoethanolamine (DPhPE), or a mixture thereof.”).
Nasr et al., in the field of nucleic acid-lined nanodiscs (Abstract), teach a MSP that is MSP1D1 (see page 18, paragraph 3).
Sligar et al., in the field of membrane scaffold proteins (Abstract), teach a detergent that is cholate (see paragraph [0077]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Boyanov et al. in view of Ivanov et al. and Stangl et al. with: (1) the teaching of Holden et al. for the purpose of increasing lipid bilayer membrane stability (see Holden et al., paragraph [0018]), (2) the teaching of Nasr et al. for the purpose of stabilizing a phospholipid bilayer in the lipid nanodisc (see Nasr et al., page 18, paragraph 3), and (3) the teaching of Sligar et al. for the purpose of disrupting hydrophobic interactions which lead to assembly or aggregation of hydrophobic and/or amphiphilic molecules into three-dimension structures (see Sligar et al., paragraph [0077]). Given the teachings of the prior art and the level of the ordinary skilled artisan at the effective filing date of the claimed invention, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Conclusion
13. No claim is allowed.
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/KAIJIANG ZHANG/Primary Examiner, Art Unit 1684