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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 22, 2026 has been entered.
Claims 1, 58, 85 and 89 are pending.
Claims 85 and 89 are withdrawn from further consideration by the examiner, 37 C.F.R. 1.142(b) as being drawn to non-elected inventions.
Claims 1 and 58, drawn to a composition comprising an sHDL nanoparticle that read on i) the phospholipid 1,2-dimyristol-sn-glycero-3- phosphocholine (DMPC); ii) the apolipoprotein mimetic described by SEQ ID NO: 4 (PVLDLFRELLNELLEALKQKLK), and iii) the tolerogenic antigens specific for celiac disease are being acted upon in this Office Action.
Priority
Applicant’ claim priority to provisional application 62/876,419, filed July 19, 2019 and 63/017,444, filed April 29, 2020, is acknowledged.
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.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency –
The specification is replete with the sequences (SEQ ID NOs: ) that are not the same sequences as in the computer readable form of sequence listing, see specification at p. 4, 9, 28, 34, 35, 36 (all sequences in Table 3), 39-49, 51-65, 74, 76 and 78. For example, at page 4, the specification discloses WDRVKDLATVYVDVLKDSGRDYVSQF (SEQ ID NO:341). However, SEQ ID NO: 341 in the computer readable form of the sequence listing is KDLEEVKAKVX.
As another example, the specification at p. 34 discloses DWLKAFYDKVAEKLKEAFPDWAKAAYDKAAEKAKEAA (SEQ ID NO: 366). However, SEQ ID NO: 366 in the computer readable form of the sequence listing is PVLDLFRELLNELLEALKKLLK.
At page 37, the specification discloses LQPFPQPELPYPQPQ (SEQ ID NO: 474), QPFPQPEQPFPWQP (SEQ ID NO: 475) and PEQPIPEQPQPYPQQ (SEQ ID NO: 476), whereas the computer form of the sequence listing for SEQ ID NO: 474 is FPEQPIPEQPQPYPQQ, SEQ ID NO: 475 is PEQPIPEQPQPYPQQ and SEQ ID NO: 476 is PQPFLPQLPYPQ.
Furthermore, the computer readable form of the sequence listing has 829 SEQ ID Nos whereas the specification has 833 SEQ ID Nos. In other words, some of the sequences in the specification are not in the computer readable form of the sequence listing.
Required response – Applicant must provide:
A computer readable form (CFR) copy of the sequence listing, a substitute paper copy of the sequence listing, as well as any amendment directing its entry into the specification, and a statement that the content of the paper and computer readable copies are the same, and where applicable, include no new matter, as required by 37 CFR 1.82(e-f) or 1.825(b) or 1.825(d).
Note, if the sequence listing text file submitted via EFS-Web complies with the requirements of 37 CFR 1.824(a)(2)-(6) and (b) (i.e., is a compliant sequence listing ASCII text file), the text file will serve as both the paper copy required by 37 CFR 1.821(c) and the computer readable form (CRF) required by 37 CFR 1.821(e), see MPEP section 500 (502.05IX).
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim objection
Claims 1 and 58 are objected to under 37 CFR 1.821 through 1.825 for failure to supply a correct sequence identifier to all disclosed sequences.
Rejection Withdrawn
The rejection of claims 52 and 58 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of the claim amendment.
The rejection of claims 1, 6, 14, 52-56 and 58 under 35 U.S.C. 103 as being unpatentable over US Patent No. 8,835,603, issued September 16, 2014; PTO 892) in view of Schwendeman et al (US20170157149, published June 8, 2017; PTO 892), Dacoba (Seminar in Immunology 24: 78-102, 2017; PTO 1449) and Reddy et al (J controlled Release 112: 26-34, 2006; PTO 892) is withdrawn in view of the claim amendment.
Claim Rejections - 35 USC § 112
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.
Claims 1 and 58 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 applicant regards as the invention.
The recitation of “(i) first polypeptide population comprising the amino acid sequence of SEQ ID NO: 474, (ii) a second polypeptide population comprising the amino acid sequence of SEQ ID NO: 475, and (iii) a polypeptide population comprising the amino acid sequence of SEQ ID NO: 476” in claim 1 is indefinite because reference to SEQ ID NO: 475-476 having no correlation to any of the sequences in the specification, see p. 37. SEQ ID NO: 474-476 cannot be searched by sequence search.
For art purpose, the search has been based on the sequences SEQ ID NO: 474 to 476 listed in the specification at p. 37.
The recitation of “(i) the first polypeptide population comprises the amino acid sequence of SEQ ID NO: 506, (ii) the second polypeptide population comprises the amino acid sequence of SEQ ID NO: 507, and (iii) the third polypeptide population comprises the amino acid sequence of SEQ ID NO: 508” in claim 58 is indefinite because reference to SEQ ID NO: 506-508 having no correlation to any of the sequences in the specification, see p. 39. SEQ ID NO: 506-508 cannot be searched by sequence search. For art purpose, the search has been based on the sequences SEQ ID NO: 506 to 508 listed in the specification at p. 39.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Moon et al (US20180078625, published Mach 22, 2018; PTO 892) in view of US Patent No. 8,835,603 (of record, issued September 16, 2014; PTO 892) in view of.
Claim 1. (Currently Amended) A composition comprising a synthetic high density lipoprotein (sHDL) nanoparticle comprising at least one phospholipid selected from 1,2-dimyristol-sn-glycero-3- phosphocholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC), an apolipoprotein mimetic having the sequence PVLDLFRELLNELLEALKQKLK (SEQ ID NO: 4), and a plurality of tolerogenic antigens comprising (i) a first polypeptide population comprising the amino acid sequence of SEQ ID NO: 474 (LQPFPQPELPYPQPQ), (ii) a second polypeptide population comprising the amino acid sequence of SEQ ID NO: 475 (QPFPQPEQPFPWQP), and (iii) a third polypeptide population comprising the amino acid sequence of SEQ ID NO: 476 (PEQPIPEQPQPYPQQ), wherein each of the tolerogenic antigens comprise an N-terminus modified with a cysteine residue bound to a linker, wherein the composition does not contain an adjuvant.
Claim 58. The composition of claim 1, wherein the plurality of tolerogenic antigens comprises (i) the first polypeptide population comprises the amino acid sequence of SEQ ID NO: 506 (PFPQRPQQPFPQ), (ii) the second polypeptide population comprises the amino acid sequence of SEQ ID NO: 507 (EQPFPQPEQPFPWQP), and (iii) the third polypeptide population comprises the amino acid sequence of SEQ ID NO: 508 (EPEQPIPEQPQPYPQQ).
Regarding claim 1, Moon teaches compositions comprising nanoparticles (e.g., synthetic high density lipoprotein (sHDL)) carrying biomacromolecule agents (e.g., nucleic acid, peptides, glycolipids, etc.), see entire document, para. [0003]. Moon teaches that the sHDL nanoparticle comprises a mixture of at least one phospholipid, e.g., dipalmitoylphosphatidylcholine (DPPC) (see para. [0018], [0019], [0052]) and at least one HDL apolipoprotein mimetic “22A” or ApoA-I mimetic 22A e.g., PVLDLFRELLNELLEALKQKLK, which is identical to the claimed PVLDLFRELLNELLEALKQKLK, (see para. [0052], [0125], [0320]) and a plurality of candidate peptides for targeted delivery of biomacromolecules, including peptides, see para. [0134], [0175]. Peptides can be readily synthesized chemically, see para. [0200]. Example of antigen is a self-antigen involved in an autoimmune disease, see para. [0166], in particular. The peptide antigen is conjugated to outer surface of the nanoparticle (see para. [0037], [0043]) via a cysteine-serine-serine (CSS) linker (see para. [0193]). The desired peptide is modified at the N-terminus with a cysteine-serine-serine (CSS) linker resulting in a complexing (linking)of the CSS-Ag with the sHDL, see para. [0194], [0321], in particular. Moon teaches that as these nanodiscs, with an established manufacturing procedure and excellent safety profiles in humans, can drastically improve delivery of antigens and adjuvant to lymph nodes (LNs), sustain antigen presentation on DCs, see para. [0006], [0007], [0319]. Nanodiscs facilitated intracellular delivery of Ag/CpG and mediated their sustained release within endosomes/lysosomes, thereby promoting durable Ag presentation, APC maturation, and cross-priming CD8α+ T-cells in vitro, se para. [0323], [0324].
Moon does not teach the plurality of tolerogenic antigens comprises (i) a first polypeptide population comprising the amino acid sequence of LQPFPQPELPYPQPQ, which is SEQ ID NO: 475, (ii) a second polypeptide population comprising the amino acid sequence of SEQ ID NO: 475 (QPFPQPEQPFPWQP), and (iii) a third polypeptide population comprising the amino acid sequence of SEQ ID NO: 476 (PEQPIPEQPQPYPQQ) for treating celiac disease as per claim 1.
However, the ‘603 patent teaches composition (col. 30, col. 33, line 15) or liposome or nano-particle (see col. 36, line 12-19) comprising one or more peptides such as i) a first peptide comprising the amino acid sequence LQPFPQPELPYPQPQ (SEQ ID NO:13) which is identical to the claimed SEQ ID NO: 475, ii) a second peptide comprising the amino acid sequence QPFPQPEQPFPWQP (SEQ ID NO:14), which is identical to the claimed SEQ ID NO: 474 (QPFPQPEQPFPWQP), and iii) a third peptide comprising the amino acid sequence PEQPIPEQPQPYPQQ (SEQ ID NO:16), which is identical to the claimed SEQ ID NO: 476 (PEQPIPEQPQPYPQQ), see entire document, Summary of invention, col. 3, line 49-65, in particular. The one or more peptides can be conjugated to an immunogenic carrier, see col. 23, line 48-50. The ‘603 patent teaches three dominant T cell stimulatory peptides which together can be used as an agent in an immunotherapy to modulate the T cell response to three or more gluten peptides and to provide tolerance to gluten, allowing treatment of celiac disease, see Summary of invention, in particular.
Examples of peptides include PEQPIPEQPQPYPQQ of SEQ ID NO: 16, which is 100% identical to the claimed SEQ ID NO: 475, see sequence alignment below:
Query Match 100.0%; Score 88; Length 15;
Best Local Similarity 100.0%;
Matches 15; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 PEQPIPEQPQPYPQQ 15
|||||||||||||||
Db 1 PEQPIPEQPQPYPQQ 15
Regarding claim 58, the patent further teaches peptide having the amino acid sequence ELQPFPQPELPYPQPQ (SEQ ID NO: 231), which is identical to the claimed SEQ ID NO: 506 (ELQPFPQPELPYPQPQ), see Table 25, reference SEQ ID NO: 231.
The patent further teaches peptide having the amino acid sequence QQPFPQPEQPFPWQP of SEQ ID NO: 232, which is 100% identical to the claimed SEQ ID NO: 507, see Table 26, reference SEQ ID NO: 232, sequence alignment below:
Query Match 100.0%; Score 95; Length 15;
Best Local Similarity 100.0%;
Matches 15; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QQPFPQPEQPFPWQP 15
|||||||||||||||
Db 1 QQPFPQPEQPFPWQP 15
The patent further teaches peptide having the amino acid sequence FPEQPIPEQPQPYPQQ of SEQ ID NO: 233, which is 100% identical to the claimed SEQ ID NO: 508, see sequence alignment below:
Query Match 100.0%; Score 94; Length 16;
Best Local Similarity 100.0%;
Matches 16; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 FPEQPIPEQPQPYPQQ 16
||||||||||||||||
Db 1 FPEQPIPEQPQPYPQQ 16
The patent further teaches peptide having the amino acid sequence EPEQPIPEQPQPYPQQ of SEQ ID NO: 233, which is identical to the claimed SEQ ID NO: 508 (EPEQPIPEQPQPYPQQ), see Table 27.
Repeated administration of the peptide is expected to induce T cell energy and/or tolerance. Ongoing regular peptide administration would be expected to maintain tolerance to gluten, suppress inflammation in the small intestine and inhibit pro-inflammatory gluten-specific T cells throughout the body, see col. 36, line 31-36. Repeat administration of peptides in saline (aka without adjuvant) over 14 consecutive days demonstrated modulation of gliadin-specific T cell responds, see col. 59, line 53-60, in particular.
In view of the combined teachings of the references, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to have linked the ‘603 patent’s peptides derived from alpha-gliadin to Moon’s synthetic high-density lipoprotein (sHDL) nanoparticle by modified each of the ‘603 patent’s peptides with CSS linker at the N-terminus as taught by Moon to arrive at the claimed invention with a reasonable expectation of success, e.g., composition comprising sHDL nanoparticle or nanodiscs comprising at least one phospholipid, e.g., dipahnitoylphosphatidylcholine (DPPC), and an apolipoprotein mimetic 22 having the amino acid sequence PVLDLFRELLNELLEALKQKLK and a plurality of peptides from alpha-gliadin for induction of tolerance to antigens specific for celiac disease.
One of ordinary skill in the art would have had a reasonable expectation of success in making and using moon’s synthetic high-density lipoprotein (sHDL) nanoparticle comprising dimyristoylphosphatidylcholine (DMPC), dipahnitoylphosphatidylcholine (DPPC) having the amino acid sequence PVLDLFRELLNELLEALKQKLK and a plurality of celiac disease specific peptides of the ‘603 patent because Moon teaches that these sHDL nanodisc offer the ability to load multiple peptides antigens and the ‘603 patent teaches that adjuvant is optional.
One of ordinary skill in the art would have been motivated to do so because Moon teaches that these sHDL nanodiscs, with an established manufacturing procedure and excellent safety profiles in humans, see col. [0319].
In addition, the claims would have been obvious because "a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense". See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
“The test of obviousness is not express suggestion of the cl aimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them.” See In re Rosselet 146 USPQ 183, 186 (CCPA 1965).
“There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.,” Motorola, Inc, v. Interdigital Tech. Corn., 43 USPQ2d 1481, 1489 (Fed. Cir. 1997).
Accordingly, the claimed invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filling date of the claimed invention especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHUONG HUYNH whose telephone number is (571)272-0846. The examiner can normally be reached on 9:00 a.m. to 6:30 p.m. The examiner can also be reached on alternate alternative Friday from 9:00 a.m. to 5:30 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Misook Yu, can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-272-0839.
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/PHUONG HUYNH/ Primary Examiner, Art Unit 1641
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