DETAILED CORRESPONDENCE
Summary
This Office Correspondence is based on the Amendment and Reply filed with the Office on 27 May 2026, regarding the Guo, et al. application.
Claims 26-39 are currently pending and have been fully considered.
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 § 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 26-39 are rejected under 35 U.S.C. 103 as being unpatentable over a US Patent Application Publication to Guo (US 2015/0267253 A1; hereinafter, “Guo”) in view of a published International Patent Application to Jayasinghe, et al. (WO 2016/055778 A1; hereinafter, “Jayasinghe”).
Regarding claim 20, Guo discloses a method of inserting a nanopore derived from a connector protein of a bacteriophage DNA packaging motor into a membrane, the method comprising contacting the membrane with a liposome comprising the nanopore, and applying a voltage across the membrane to induce liposome-membrane fusion ([0220]- "reconstituting the connector into liposomes was developed by co-incubation of the connector with the lipid"; [0222]- "showed that direct incubation of the connector protein with liposomes or with a planar lipid bilayer did not lead to channel formation in the bilayer membrane (FIG. 6A). Connector insertion into the bilayer only occurred when the connector protein-reconstituted proteoliposomes were fused into the bilayer (FIG. 6B-C). The channel insertion was observed through a discrete step-wise increase in conductance as shown in a continuous current trace (FIG. 6), under either positive or negative transmembrane voltage").
Guo does not teach that the membrane is a copolymer membrane.
However, Jayasinghe teaches mutant forms of Msp (a nanopore), wherein is taught copolymer membranes (p. 45, lines 10-15 - “Suitable membranes are well-known in the art. The membrane is preferably an amphiphilic layer. An amphiphilic layer is a layer formed from amphiphilic molecules, such as phospholipids, which have both hydrophilic and lipophilic properties. The amphiphilic molecules may be synthetic or naturally occurring. Non-naturally occurring amphiphiles and amphiphiles which form a monolayer are known in the art and include, for example, block copolymers…”).
At the time of the filing of the present application, it would have been obvious to one of ordinary skill in the art to have utilized the copolymer membrane taught by Jayasinghe as the membrane disclosed by Guo because triblock copolymer are synthesized, and the exact construction can be carefully controlled to provide the correct chain lengths and properties required to form membranes and to interact with pores and other proteins (Jayasinghe, p. 46, lines 2-4).
Regarding claim 27, Guo further teaches wherein the connector protein of a bacteriophage DNA packaging motor is modified compared to the wild-type connector protein ([0045]- "viral DNA-packaging motor protein connectors with C-terminal modification").
Regarding claim 28, Guo further discloses wherein the nanopore comprises the aperture forming region of a connector protein of a bacteriophage DNA packaging motor (claim 8- "all or a transmembrane aperture-forming portion of bacteriophage phi29 DNA-packaging motor connector protein polypeptide").
Regarding claim 29, Guo further discloses wherein the aperture forming region is modified to alter one or more property of the channel of the nanopore ([0078] – “… the present viral DNA-packaging motor protein connectors, and also provide advantageous analyte characterization capabilities that may derive in part from the stable membrane incorporation of a protein conductive channel that can be engineered or mutated to have desired functional properties such as any of a wide variety of analyte accessible affinity interaction domains by which to engage analyte in a specific binding interaction.”)
Regarding claim 30, Guo further discloses wherein the nanopore comprises a full length connector protein of a bacteriophage DNA packaging motor ([0018] – “… the viral DNA-packaging motor connector protein comprises a homododecamer of viral DNA-packaging motor connecting protein polypeptide subunits …”).
Regarding claim 31, Guo further discloses wherein the nanopore comprises a truncated connector protein of a bacteriophage DNA packaging motor ([0127] – “A truncated molecule may be any molecule that comprises less than a full length version of the molecule, for example, a truncated viral DNA-packaging motor protein polypeptide subunit.”).
Regarding claim 32, Guo further discloses wherein the nanopore is a multimeric protein formed of six or more subunits ([0025] – “a plurality of isolated viral DNA-packaging motor connector protein subunit polypeptides that are capable of self-assembly into a homododecameric viral DNA-packaging motor connector protein, to obtain a membrane that comprises a lipid bilayer in which is incorporated the viral DNA-packaging motor connector protein under conditions and for a time sufficient for said connector protein to form an aperture …”).
Regarding claim 33, Guo further discloses wherein the nanopore is a dodecameric protein ([0025] – “a plurality of isolated viral DNA-packaging motor connector protein subunit polypeptides that are capable of self-assembly into a homododecameric viral DNA-packaging motor connector protein, to obtain a membrane that comprises a lipid bilayer in which is incorporated the viral DNA-packaging motor connector protein under conditions and for a time sufficient for said connector protein to form an aperture …”).
Regarding claim 34, Guo discloses wherein one or more of the subunits are modified at the C-terminus and/or N-terminus ([0028] – “… a homododecamer of viral DNA-packaging motor connector protein polypeptide subunits, wherein each of said subunits comprises a fusion protein which comprises (a) an aperture domain that comprises an isolated viral connector protein polypeptide having an amino terminus and a carboxy terminus; (b) at least one flexibility domain that comprises a polypeptide of 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 or 18 contiguous uncharged amino acids and that is fused to at least one of the amino terminus and the carboxy terminus of (a) …”).
Regarding claim 35, Guo discloses wherein one or more of the subunits are modified at the C-terminus and/or N-terminus to increase the hydrophilicity at one or both ends of the nanopore ([0124] – “… aperture having desirable properties, such as increased aperture dimensions and/or altered distribution of hydrophilic, hydrophobic, neutral and/or charged amino acid side chains and/or preservation of the conductive aperture structure despite truncation of the viral DNA-packaging motor connector protein sequence or addition of polypeptide domains ..”).
Regarding claim 36, Guo discloses wherein one or more of the subunits are modified by the addition of a flexible linker and a peptide tag at the C-terminus and/or N-terminus ([0218] – “To facilitate connector purification, an affinity/alignment domain comprising a C-terminal His (His6) or Strep-II (WSHPQFEK) tag was inserted just downstream of a flexibility domain comprising a six glycine linker for improved affinity tag flexibility.”).
Regarding claim 37, Guo discloses wherein the subunits are identical ([0025] – “… a plurality of isolated viral DNA-packaging motor connector protein subunit polypeptides that are capable of self-assembly into a homododecameric viral DNA-packaging motor connector protein …”).
Regarding claim 38, Guo discloses wherein the bacteriophage DNA packaging motor is phi29 ([0020] – “In certain embodiments the viral DNA-packaging motor connector protein comprises a homododecamer of viral DNA-packaging motor connector protein polypeptide subunits that each comprise a polypeptide selected from (i) all or a transmembrane aperture-forming portion of bacteriophage phi29 DNA-packaging motor connector protein polypeptide having the amino acid sequence set forth in SEQ ID NO: 1.”).
Regarding claim 39, Jayasinghe discloses wherein the copolymeric membrane is a triblock (p. 6, lines 2-4 – “… subunits may be suspended in a purified form in a solution containing a triblock copolymer membrane such that it diffuses to the membrane and is inserted by binding to the membrane and assembling into a functional state.”) or a deblock copolymer membrane (p. 45, lines 23-24 – “The block copolymer may be a diblock (consisting of two monomer sub-units) …”).
Response to Arguments
Applicant's arguments filed 27 May 2026, have been fully considered but they are not persuasive. Applicant argues, “… the combination of Guo and Jayasinghe fails to render obvious the method of claim 26 … The Office Action’s proposed combination lacks both a motivation to combine and a reasonable expectation of success (Remarks, p. 4). In response, the Examiner points to the fact that Jayasinghe teaches both membranes of copolymers, as outlined in the rejection above, and lipid bilayers (p. 46, lines 25-34). As such, these two types of membranes can be seen as alternatives to each other. Thus, it would be reasonable to one of ordinary skill in the art to have made the substitution of the lipid bilayer taught by the Guo reference for the copolymer membrane described also by the Jayasinghe reference with an expectation of some degree of success.
Interview with the Examiner
If at any point during the prosecution it is believe an interview with the Examiner would further the prosecution of an application, please consider this option.
The Automated Interview Request form (AIR) is available to request an interview to be scheduled with the Examiner. First, an authorization for internet communications regarding the case should be filed prior or with an AIR online request.
The internet communication authorization form (SB/0439), which authorizes or withdraws authorization for internet-based communication (e.g., video conferencing, email, etc.) for the application must be signed by the applicant or the attorney/agent for applicant. The form can be found at:
https://www.uspto.gov/sites/default/files/documents/sb0439.pdf
The AIR form can be filled out online, and is automatically forwarded to the Examiner, who will call to confirm a requested time and date, or set up a mutually convenient time for the interview. The form can be found at:
https://www.uspto.gov/patent/uspto-automated-interview-request-air-form.html
The Examiner encourages, but does not require, interviews by the USPTO Microsoft Teams video conferencing. This system allows for file-sharing along audio conferencing. Microsoft Teams can be used as an internet browser add-on in Microsoft IE, Google Chrome, or Mozilla Foxfire, or as a temporary Java-based application on these browsers. Steps for joining an Examiner setup Microsoft Teams can be found at the USPTO website:
https://www.uspto.gov/patents/laws/interview-practice#step3
Additionally, a blank email to the Examiner at the time of a telephonic interview can be used for a reply to easily allow for Microsoft Teams communication. Please note, policy guidelines regarding Internet communications are detailed at MPEP §500-502.3, and office policy regarding interviews are detailed at MPEP §713.
Conclusion
THIS ACTION IS MADE FINAL. 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 JOHN C BALL whose telephone number is (571)270-5119. The examiner can normally be reached on M - F, 9 am - 5:30 pm.
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, Luan Van can be reached on (571)272-8521. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J. Christopher Ball/ Primary Examiner, Art Unit 1795
Prosecution Insights