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 .
Status of Application, Amendments and/or Claims
The amendment of 16 March 2026 has been entered in full. Claims 1, 6, and 29 are amended. Claims 2-4, 7-28, 30, 36, 40, 41, 43-47, and 49-217 are cancelled. Claims 218-220 are added.
Claims 1, 5, 6, 29, 31-35, 37-39, 42, 48, and 218-220 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1, 5, 6, 29, 31-35, 37-39, 42, 48, and 218-220 in the reply filed on 16 March 2026 is acknowledged.
Claims 1, 5, 6, 29, 31-35, 37-39, 42, 48, and 218-220 are under consideration in the instant application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 16 March 2026 and 02 February 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The replacement drawings were received on 14 November 2023. These drawings are acceptable.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
1. Specific deficiencies and the required response to this Office Action are as follows:
1a. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d) (see Figure 9A; the sequence termed, “EETI-II”). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
1b. Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosure located in Figure 9A (specifically, the sequence termed, “C16-EETI-II”) is not contained in the Sequence Listing or CRF.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Specification
2. The disclosure is objected to because of the following informalities:
2a. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see page 44, line 20). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
Claim Objections
3. Claims 6, 31, 32, 48, and 218-220 are objected to because of the following informalities:
3a. Claim 6 recites the acronyms “DMPC”, “DOPC”, “DOPS”, “DOPE”, and “DPPC” without first defining what they represent. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym and/or in each independent claim.
3b. Claim 31 recites the acronym “PEG” without first defining what it represents. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym and/or in each independent claim.
3c. Claim 32 recites the acronym “MW” without first defining what it represents. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym and/or in each independent claim.
3d. Claim 220 recites the acronyms “EETI-II”, MCoTI 1”, and “SOTI 1” without first defining what they represent. While the claims can reference acronyms, the material presented by the acronym must be clearly set forth at the first use of the acronym and/or in each independent claim.
3e. Claims 48 and 218-220 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
4. Claims 32, 34, and 37-39 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
4a. Claim 32 is rejected as being vague and indefinite for omitting the measured units (i.e., Daltons, kilodaltons, g/mol, etc.) and the method by which the molecular weight is calculated that determines the numerical value. For example, an 1500 kD protein separated by SDS-PAGE may not have the same molecular weight if separated via a different method (i.e., 2D gel).
4b. Claims 37-39 are rejected as being indefinite because claims 37 and 38 recite the limitation “said two or more antigen-binding polypeptides” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 1, from which claims 37 and 38 depend, does not recite “two or more antigen-binding polypeptides”. Claim 1 only recites “an antigen-binding polypeptide”.
4c. Claim 34 is rejected as being indefinite because the claim requires that said conjugate increases the activity of said antigen-binding polypeptide, wherein said activity is OX40 binding and said conjugate has 4-8 molecules of said antigen-binding polypeptide. It is not clear how OX40 binding activity is increased when claims 1 and 33 do not recite any specific elements directed to OX40 or OX40L. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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.
5. Claims 1, 5, 6, and 42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Blanchette et al. (US 2019/0307692; published 10 October 2019 or WO 2017/155837). It is noted that US 2019/0307692 and WO 2017/155837 have the same disclosure. Thus, for brevity, relevant portions of US 2019/0307692 will be cited below.
Blanchette et al. teach a nanolipoprotein particle comprising a membrane-forming lipid, one or more lysolipids, a hydrophobically anchorable target molecule, and a scaffold protein, meeting the limitations of instant claim 1 (page 1, [0010]). Blanchette et al. teach that the hydrophobically anchorable target molecule in the nanolipoprotein particle is an antibody, meeting the limitation of an antigen-binding polypeptide of instant claim 1 (page 14, [0122-0123]). Blanchette et al. disclose that the membrane-forming lipid and the one or more lysolipids are arranged in a lipid bilayer stabilized by the scaffold protein (page 1, [0010-0012]). Blanchette et al. indicate that the membrane-forming lipids are typically arranged in a membrane lipid bilayer confined by the scaffold protein in a discoidal configuration, meeting the limitations of instant claim 1 (page 3, [0030]). Blanchette et al. teach that the membrane-forming lipid in the nanolipoprotein particle is functionalized, meeting the limitations of instant claim 1 (page 13, [0110]; page 11, [0095-0096]). Specifically, Blanchette et al. disclose that the lysolipids-incorporated nanolipoprotein particles can further comprise other functional molecules embedded in the membrane lipid bilayer, conjugated to a lipophilic anchor compound inserted into the membrane bilayer, or conjugated through binding of a functional group with a corresponding functional group presented on functionalized membrane forming lipid of the membrane lipid bilayer, meeting the limitations of instant claim 1 (page 13, [0114]).
Blanchette et al. disclose that a scaffold protein includes apolipoproteins, such as Apolipoproteins A, Apolipoproteins B, Apolipoproteins C, Apolipoproteins D, Apolipoproteins E, and Apolipoproteins H, meeting the limitations of instant claim 5 (page 3, [0032-0033]; page 9, [0077]).
Blanchette et al. teach that membrane-forming lipid, amphipathic lipid, or polar lipid includes, for example, DMPC, DOPE, DOPC, DPPC, meeting the limitations of instant claim 6 (page 3, [0031]).
Blanchette et al. indicate that the nanolipoprotein particle can be included in pharmaceutical compositions together with an excipient or diluent, meeting the limitations of instant claim 42 (page 16, [0143-0146]).
6. Claims 1, 5, 6, 29, 31, 32, 33, 35, and 42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wong et al. (Bioconjugate Chem 31: 743-753, 2020; published 21 January 2020; cited on the IDS of 16 March 2026).
Wong et al. teach lipid nanodiscs (LNDs) wherein the LNDs comprise a lipid bilayer encircled by two molecules of recombinant scaffold proteins (MSPs) and wherein an anti-CEA antibody or its Fab’ fragment is covalently attached, meeting the limitations of instant claims 1 and 29 (page 743, column 1, last paragraph; page 744, scheme 1; abstract). Wong et al. disclose that MSPs are truncated versions of Apo-A1, meeting the limitations of instant claim 5 (page 743, column 1, last paragraph). Specifically, Wong et al. generate LNDs with the incorporation of the 1,2-distearoyl-sn-glycero-3-phosphoethanoloamine-n-[dibenzocyclooctyl(polyethylene glycol)-2000] lipid (DSPE-PEG2000-DBCO), meeting the limitations of instant claims 31 and 32 (page 744, column 1; scheme 1). Wong et al. state that MSP1D1 is utilized to generate a LND size of about 10 nm with 160 dimyristyphospholipids (DMPCs) per LND (wherein at least one 1 targeting moiety is conjugated per LND), meeting the limitations of instant claims 6 and 31 (page 744, column 2; page 750, column 1, last paragraph). Wong et al. teach that anti-CEA IgG or its Fab’ fragment are alkylated on their hinge region sulfhydryl groups with bromoacetamido-PEG5 azide, derivatized with NHS-DOTA, and clicked to DSPE-PEG2000-DBCO LND (page 746, column 1, last paragraph through column 2; scheme 1). Lastly, Wong et al. disclose administering the antibody-targeted LNDs to CEA transgenic mice, meeting the limitations of instant claim 42 (pages 747-748; Figures 5-6).
Conclusion
Claims 1, 5, 6, 29, 31-35, 37-39, and 42 are rejected. Claims 48 and 218-220 are objected.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Hannoush et al. US 2017/0129927 (cysteine knot scaffold platforms)
Darwish et al. Nanoscal Adv 3: 3929-3941, 2021 (teachings of the instant specification)
Denisov et al. Chem Rev 117: 4669-4713, 2017 (review of nanodiscs)
Iovannisci et al. Biochem Biophys Res Comm 379: 466-469, 2009 (construct a single chain variable antibody (scFV)-apolipoprotein chimer and form nanodisks (pages 466-467; Fig 1)
Ryan, R.O. Exp Opin Drug Delivery 5(3): 343-351, 2008 (review of nanodisks)
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BEB
Art Unit 1647
21 April 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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