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 .
Priority
Applicant’s claim for the benefit of a prior-filed application (has PRO 63/325,737, filed on March 31, 2022) under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3-4, 7, 13 are rejected under 35 U.S.C. 103 as being unpatentable over CLARKE et al. (US20140262784A1, hereinafter as CLARKE) in view of BROŽ et al. (Cell targeting by a generic receptor-targeted polymer nanocontainer platform, 2005, hereinafter BROŽ).
Regarding Claim 1, CLARKE discloses a nanopore detection/sequencing system in which an analyte is coupled to a membrane containing the relevant detector, thereby positioning the analyte and detector in the same membrane system for detection (¶[0007]).
The amphiphilic layer of the membrane is formed from block copolymers, which include two or more monomer subunits polymerized into a single polymer chain. One subunit is hydrophobic and the other subunit or subunits are hydrophilic in aqueous media, allowing the polymer to form a biological-membrane-like structure. The disclosed polymer configurations include diblock, triblock, and higher block-count copolymers, with the triblock configuration having a hydrophilic-hydrophobic-hydrophilic arrangement. The disclosed hydrophobic polymers include siloxane and other non-hydrocarbon based polymers, and the triblock copolymer membrane provides increased mechanical and environmental stability compared with biological lipid membranes (¶[0090]–¶[0093]).
The sequencing methods are carried out using an artificial membrane, which forms a barrier to the flow of ions, nucleotides, and polynucleotides. The apparatus has a chamber containing an aqueous solution and a barrier separating the chamber into two sections, with the barrier having an aperture in which the membrane is formed (¶¶[0230]–[0234]).
In Example 5, the chip has 128 wells with platinum electrodes and a 30 μm aperture. The monolayers are formed from a 50 mg/mL triblock copolymer solution of TBCP 6-33-6, identified as OH-PMOXA-(PEG linker)-PDMS-(PEG linker)-PMOXA-OH, having PMOXA blocks on both sides of the PDMS middle block and hydroxyl end groups at both terminal ends (¶¶[0332]–[0333]).
However, CLARKE does not explicitly disclose “wherein the end groups are selected from the group consisting of: fluorenylmethoxycarbonyl (Fmoc), tert-butyl carbamate (NHBoc), methyl (CH₃), biotin, thiol (SH), and sulfonate (SO₃⁻).”
BROŽ discloses biotin-functionalized poly(2-methyloxazoline)-b-poly(dimethylsiloxane)-b-poly(2-methyloxazoline) triblock copolymers that are self-assembled to form nanocontainers, with biotinylated targeting ligands attached using streptavidin as a coupling agent. The nanocontainers are programmable toward specific targets and are suitable as carriers of complex functionality, with receptor-specific binding followed by vesicular uptake (Abstract, pg. 475).
FIG. 1a illustrates the triblock ABA copolymer poly(2-methyloxazoline)-b-poly(dimethylsiloxane)-b-poly(2-methyloxazoline) (PMOXA-PDMS-PMOXA), with hydrophilic PMOXA blocks on both sides of a hydrophobic PDMS block and biotin groups at the terminal ends of the hydrophilic blocks. The amphiphilic block copolymer forms stable, closed vesicular structures in aqueous media, and the container walls are completely covered by PMOXA chains that exhibit very low nonspecific protein binding (pgs. 476–477).
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FIG. 1a of BROŽ
In Nanocontainer synthesis, the polymer consists of a PDMS middle block and two PMOXA side chains. To obtain active drug delivery systems, the ends of the triblock copolymer are functionalized with biotin groups by reacting the polymer with excess biotin in chloroform in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethylamino)pyridine (DMAP). Biotinylated nanocontainers are prepared using a mixture of unmodified triblock copolymer and biotinylated polymer at a ratio of 9:1 wt/wt (Section 2.1, pgs. 477–479).
In Nanocontainer functionalization with polyG ligands, the biotinylated nanocontainers are incubated with a slight excess of streptavidin with respect to the biotin groups at the surface of the nanocontainers. The nanocontainers are then incubated with biotinylated polyG in a 1:1 ratio of biotin sites to polyG to produce active targeting drug delivery systems (Section 2.2, pg. 479).
The triblock copolymers disclosed by BROŽ provide biotin groups at the surface of the nanocontainers for binding streptavidin, which serves as a coupling agent for attaching biotinylated polyG targeting ligands to produce active targeting drug delivery systems (Section 2.2, pg. 479). In view of CLARKE’s amphiphilic triblock copolymer membrane having hydrophilic PMOXA end blocks, a person skilled in the art would incorporate the biotin end-group functionalization at the terminal ends of the PMOXA blocks to predictably provide surface coupling sites for streptavidin-mediated attachment of functional ligands.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate the biotin end-group functionalization, as disclosed by BROŽ, into the terminal ends of the hydrophilic PMOXA blocks in the amphiphilic triblock copolymer membrane by CLARKE.
Regarding Claim 3, modified CLARKE makes obvious the barrier of Claim 1. CLARKE discloses in Example 5 a triblock copolymer solution of TBCP 6-33-6, identified as OH-PMOXA-(PEG linker)-PDMS-(PEG linker)-PMOXA-OH (¶¶[0332]–[0333]). PDMS is the hydrophobic block.
Regarding Claim 4, modified CLARKE makes obvious the barrier of Claim 1. CLARKE discloses the block copolymer has a diblock configuration (¶[0091]).
Regarding Claim 7, modified CLARKE makes obvious the barrier of Claim 1. CLARKE discloses a triblock copolymer configuration having a hydrophilic-hydrophobic-hydrophilic arrangement, with two hydrophilic blocks positioned on opposite sides of a hydrophobic block (¶¶[0091]–[0093]).
Regarding Claim 13, modified CLARKE makes obvious the barrier of Claim 1. CLARKE discloses an artificial membrane forming a barrier between two sections of a chamber, with a pore present in or inserted into the membrane and providing contact across the membrane between the two sections (¶¶[0230]–[0234]). In Example 5, the MspA nanopore is added to the chip in buffer and inserted into the triblock copolymer membrane (¶¶[0332]–[0336]).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over CLARKE in view of BROŽ as applied to claim 1 above, and further in view of GRZELAKOWSKI (US20170113193A1).
Regarding Claim 5, modified CLARKE makes obvious the barrier of Claim 1. However, modified CLARKE does not explicitly disclose “the hydrophobic block is polybutadiene (PBd).”
GRZELAKOWSKI discloses a filtration membrane including a porous support and a layer of vesicles covalently bonded to the support surface, with the vesicles including transmembrane proteins and formed from an amphiphilic block copolymer (¶[0007]).
The amphiphilic block copolymer is a diblock copolymer AB having a hydrophilic block and a hydrophobic block, or a triblock copolymer ABA having hydrophilic end blocks and a hydrophobic inner block. The hydrophobic block includes polymers such as polydimethylsiloxane, polyisoprene, and polybutadiene (PBd) (¶¶[0085]–[0086]).
In Example 4, a diblock copolymer polybutadiene-PMOXA is prepared using functionalized polybutadiene as a macro-initiator for polymerization of 2-methyl-2-oxazoline to form PBd-PMOXA. The resulting PB₁₂-PMOXA₅-NH-(CH₂)₂-NH₂ polymer is used to prepare vesicles (¶¶[0613]–[0622]).
The PBd hydrophobic block disclosed by GRZELAKOWSKI provides a known alternative hydrophobic block material for amphiphilic copolymer membrane formation, with the additional ability to be internally crosslinked (¶¶[0085]–[0086], [0553]). In view of modified CLARKE’s amphiphilic block copolymer barrier having a hydrophobic siloxane/PDMS block, a person skilled in the art would use PBd for the hydrophobic block as a known alternative hydrophobic block material to predictably provide a hydrophobic block capable of internal crosslinking.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to use polybutadiene (PBd), as disclosed by GRZELAKOWSKI, for the hydrophobic block in the barrier of modified CLARKE.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over CLARKE in view of BROŽ as applied to claim 1 above, and further in view of KUMAR et al. (US20140051785A1, KUMAR).
Regarding Claim 8, modified CLARKE makes obvious the barrier of Claim 1. However, modified CLARKE does not explicitly disclose “the hydrophobic block is poly(isobutylene) (PIB).”
KUMAR discloses high density membranes comprising block copolymers and membrane proteins, as well as methods for producing such membranes (¶[0004]). Suitable amphiphilic block copolymers include polyisobutylene (PIB) as a hydrophobic block and polymethyloxazoline (PMOXA) as a hydrophilic block, with embodiments including diblock and triblock copolymers (¶¶[0045]–[0046]).
The hydrophobic blocks disclosed by KUMAR, including PIB, are used with hydrophilic blocks including PMOXA to form amphiphilic block copolymers, with block selection used to tailor membrane physical properties and morphology (¶¶[0008], [0045]–[0046]). In view of modified CLARKE’s amphiphilic block copolymer barrier having hydrophilic PMOXA blocks and a hydrophobic PDMS block, a person skilled in the art would use PIB for the hydrophobic block as a known alternative performing the same hydrophobic-block function in combination with PMOXA.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to use polyisobutylene (PIB), as disclosed by KUMAR, for the hydrophobic block in the barrier of modified CLARKE.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over CLARKE in view of BROŽ as applied to claim 1 above, and further in view of MEIER et al. (US20020037986A1, hereinafter MEIER).
Regarding Claim 11, modified CLARKE makes obvious the barrier of Claim 1. However, modified CLARKE does not explicitly disclose “the block copolymer is a triblock copolymer having two hydrophobic blocks and one hydrophilic block.”
MEIER discloses membranes made from segmented amphiphilic A+B copolymers, where A is hydrophilic and B is hydrophobic, and the copolymers self-assemble when dispersed in water. The membranes are freestanding or supported on a substrate, and the copolymer configurations include triblock ABA and BAB copolymers (¶[0006]). The amphiphilic segmented copolymer configurations include an A-B diblock, a B-A-B triblock having one A segment and two B segments attached to its termini, and an A-B-A triblock having one B segment and two A segments attached to its termini (¶[0046]).
The BAB triblock configuration provides a known alternative amphiphilic segment arrangement having two hydrophobic blocks and one hydrophilic block for self-assembled planar membrane formation (¶¶[0006]–[0007], [0046]). In view of modified CLARKE’s amphiphilic block copolymer barrier, a person skilled in the art would use the BAB triblock configuration as an alternative triblock arrangement to predictably provide a self-assembled amphiphilic membrane having two hydrophobic blocks and one hydrophilic block.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to use the BAB triblock configuration, as disclosed by MEIER, for the block copolymer in the barrier of modified CLARKE.
Response to Arguments
Applicant’s arguments filed July 16, 2026, with respect to the previous rejections have been fully considered and are persuasive. Therefore, the previous rejections have been withdrawn. However, upon further consideration, new grounds of rejection are made under 35 U.S.C. § 103 over CLARKE in view of BROŽ, GRZELAKOWSKI, KUMAR, and MEIER.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAK L. CHIU whose telephone number is (703)756-1059. The examiner can normally be reached M-F: 9:00am - 6:00pm (CST).
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/TAK L. CHIU/Examiner, Art Unit 1771
/KRISHNAN S MENON/Primary Examiner, Art Unit 1771
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