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 .
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Claims 85 and 89 are withdrawn from further consideration by the examiner, 37 C.F.R. 1.142(b) as being drawn to non-elected inventions.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 updated computer-readable sequence listing submitted on September 14, 2026 where the identifiers do not correspond to the sequence identifiers in the substituted specification. Specifically, the computer readable form of the sequence listing has a total of 829 SEQ ID Nos whereas the specification has 833 SEQ ID Nos, see p. 76 and 78. In other words, SEQ ID NO: 830-833 are not in the computer readable form of the sequence listing.
The sequences of “SEQ ID NO: 474 (FPEQPIPEQPQPYPQQ),…SEQ ID NO: 475 (PEQPIPEQPQPYPQQ), and … SEQ ID NO: 476 (PQPFLPQLPYPQ)” from the computer readable form of the sequences listing do not correlated with the sequences disclosed in the specification.
The substitute specification filed September 14, 2026 at p. 41 discloses:
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The sequences of SEQ ID NO: 506 (QQPFPQPEQPFPWQP)…SEQ ID NO: 507 (FPEQPIPEQPQPYPQQ) and …SEQ ID NO: 508 (PELP)” from the computer readable form of the sequences listing do not correlated with the sequences disclosed in the specification.
For example, the specification discloses:
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The sequence PELP in the specification is SEQ ID NO: 512 (see Table above), but the same sequence in the sequence listing is SEQ ID NO: 508.
The sequences of SEQ ID NO: 341 to SEQ ID NO: 346 at p. 34, lines 10 to 12 do not correspond the sequences in the computer form of the sequence listing.
The sequences starting from SEQ ID NO: 347 at p. 35, lines 1 to line 17 do not correspond the sequences in the computer readable form of the sequence listing.
The sequence LQPFPQPELPYPQPQ (SEQ ID NO: 474) at p. 37 do not match with the SEQ ID NO: 474 (FPEQPIPEQPQPYPQQ) in the computer readable form of the sequence listing.
In addition to items A-G above, Applicant’s assistance is requested to correct all SEQ ID Nos for all sequences at p. 37, 38, 42-49, 60-61, 64, 65, 76 and 78 of the specification to match the SEQ ID NO in the computer readable form of the sequence listing.
Required response – Applicant must provide:
A replacement "Sequence Listing XML" part of the disclosure, as described above submitted in accordance with either items A to H; together with
A statement that identifies the location of all additions, deletions, or replacements of sequence information in the replacement "Sequence Listing XML" as required by 1.835(b)(3);
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
A statement that the replacement "Sequence Listing XML" includes no new matter as required by 37 CFR 1.835(b)(5); and
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation-by-reference paragraph as required by 37 CFR 1.835(b)(2), 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.
Specification
The substitute specification filed September 14, 2026 has been entered.
Applicant’s assistance is requested to correct any errors of which applicant may become aware in the specification. Appropriate correction is required.
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.
Regarding claim 1, the claim recites the sequences of “SEQ ID NO: 474 (FPEQPIPEQPQPYPQQ),…SEQ ID NO: 475 (PEQPIPEQPQPYPQQ), and … SEQ ID NO: 476 (PQPFLPQLPYPQ)”, which correspond to the computer readable form of the sequences, but these sequences do not correlated with the sequences disclosed in the specification.
For example, the substitute specification filed September 14, 2026 at p. 41 discloses:
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As such, one of ordinary skill in the art would not reasonably be apprised of the metes and bounds of the invention.
Regarding claim 58, claim 58 recites the sequences of “…SEQ ID NO: 506 (QQPFPQPEQPFPWQP)…SEQ ID NO: 507 (FPEQPIPEQPQPYPQQ) and …SEQ ID NO: 508 (PELP)”, but these sequences do not correlated with the sequences disclosed in the specification.
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As such, one of ordinary skill in the art would not reasonably be apprised of the metes and bounds of the invention.
Claim 58 recites the limitation “…SEQ ID NO: 506 (QQPFPQPEQPFPWQP)…SEQ ID NO: 507 (FPEQPIPEQPQPYPQQ) and …SEQ ID NO: 508 (PELP)” in base claim 1. There is insufficient antecedent basis for this limitation in the claim. This is because the sequences in claim 1 are SEQ ID NO: 4 (VLDLFRELLNELLEALKQKLK), SEQ ID NO: 474 (FPEQPIPEQPQPYPQQ), SEQ ID NO: 475 (PEQPIPEQPQPYPQQ), and SEQ ID NO: 476 (PQPFLPQLPYPQ).
For art purpose, the search has been based on the sequences SEQ ID NO: 474 to 476 listed in the specification at p. 37.
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).
Claims 1 and 58 are 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) and US20170157149 (newly cited, published June 8, 2017; PTO 892).
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 (QQPFPQPEQPFPWQP), (ii) the second polypeptide population comprises the amino acid sequence of SEQ ID NO: 507 (FPEQPIPEQPQPYPQQ), and (iii) the third polypeptide population comprises the amino acid sequence of SEQ ID NO: 508 (PELP).
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 (SEQ ID NO: 4), (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 LQPFPQPELPYPQPQ of SEQ ID NO: 474, (ii) a second polypeptide population comprising the amino acid sequence QPFPQPEQPFPWQP of SEQ ID NO: 475, and (iii) a third polypeptide population comprising the amino acid sequence PEQPIPEQPQPYPQQ of SEQ ID NO: 476 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: 474, ii) a second peptide comprising the amino acid sequence QPFPQPEQPFPWQP (SEQ ID NO:14), which is identical to the claimed SEQ ID NO: 475 (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 QQPFPQPEQPFPWQP of SEQ ID NO: 232, which is 100% identical to the claimed SEQ ID NO: 506, 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: 507, 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
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Db 1 FPEQPIPEQPQPYPQQ 16
The patent further teaches SEQ ID NO:13 (LQPFPQPELPYPQPQ) encompasses two overlapping epitopes, PFPQPELPY (SEQ ID NO:3) and PQPELPYPQ (SEQ ID NO:4), see Summary of invention, in particular. The term “comprising” is open ended. It expands the peptide to include additional residues at both ends.
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. The ‘603 patent further teaches that adjuvant is optional, see col. 6, line 58, in particular.
Evidentiary reference schwendeman (US20170157149) teaches that the sHDL nanoparticle comprises DMPC, DPPC and an apolipoprotein mimetic 22A peptide PVLDLFRELLNELLEALKQKLK (SEQ ID NO: 35), which is identical to the claimed SEQ ID NO: 4 (see para. [0229]), is useful for treating autoimmune disease, e.g., celiac disease, see para. [0215]).
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 from alpha-gliadin with CSS linker at the N-terminus as taught by Moon with a reasonable expectation of success, e.g., linking the peptides to the high-density lipoprotein (sHDL) nanoparticle or nanodiscs for treating autoimmune disease such as celiac disease as taught by schwendeman by 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 linked to a plurality of celiac disease specific peptides via an N-terminus modified with a cysteine residue bound to a linker, e.g., CSS 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]) and Schwendeman teaches the sHDL nanoparticle can be used for treating various autoimmune disease such as celiac disease.
One of ordinary skill in the art would have been motivated to do so because the ‘603 patent teaches that these immunodominant peptides are useful in the treatment of celiac disease by specifically modifying the pathogenic T cell response to gluten and to therefore provide a vaccine effective against celiac disease.
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.
Applicants’ arguments filed September 14, 2026 have been fully considered but are not found persuasive.
Applicants’ position is that Moon, however, is directed to immunostimulatory vaccine nanodiscs and does not teach or suggest the presently claimed adjuvant-free tolerogenic composition for celiac disease. The working examples relied on antigen together with the adjuvant CpG, and Moon describes CpG as triggering TLR9 activation and enhancing responses to peptide or protein antigens. Moon also states that an adjuvant is especially useful when the antigen is relatively weak. Thus, at most, Moon would have suggested using its sHDL platform to enhance immune stimulation in the presence of an adjuvant, not to induce tolerance using an adjuvant-free composition containing the '603 patent gliadin peptides.
From these statements, there would have been no motivation to combine the '603 patent with Moon. The technology of the '603 patent is directed toward a combination of three peptides in a formulation-Examples 3 and 4 of the '603 patent describe the components of the eventual product that spawned from this technology, a vaccine for celiac disease patients known as "Nexvax2". Nexvax2 is an equimolar combination of three analogous peptide sequences to the peptides of present claim 1, instead having N-terminal pyroglutamate residues, formulated in saline. The '603 patent describes how, after dosing mice with this formulation of peptides, lymph nodes were harvested and the combination stimulated T cell proliferation (Fig. 10 of the '6034 patent) accordingly, the '603 patent does not indicate lymph node trafficking required improvement to increase Nexvax2 potency.
Furthermore, at the time of filing the instant application, it was reported from the phase II trial for Nexvax2 (NCT03644069) that this combination of peptides failed to provide any difference for tolerization in non-homozygous celiac patients compared to placebo and was discontinued. The Nexvax2 trial measured a change in celiac disease patient reported outcomes (CeD PRO), the CeD PRO reporting on a scale of 0 (absent or no symptoms) to 10 (most severe symptoms, see NCT03644069 Primary Outcome Measures). The analysis of data from the phase II study patients revealed a change in CeD PRO from baseline in Nexvax2 patients of 2.86 compared to 2.63 in patients receiving placebo (p = 0.43, see Tye-Din, J.A. et al. Lancet Gastroenterol. Hepatol., 2023, 8, 446-457, Findings). Accordingly, it was known in the prior art at the time of filing the instant application that the combination of instant SEQ ID NOs: 474, 475, and 476 was ineffective for achieving tolerization.
Based on the cited references, the skilled person would not have had a reasonable expectation that combining the '603 patent peptides with Moon's sHDL nanoparticle would yield the claimed adjuvant-free tolerogenic composition. The '603 patent peptides were known as celiac-disease epitopes, but the cited disclosure does not show that placing those peptides on an sHDL nanodisc, without adjuvant, would produce clinically meaningful tolerization. Moon's teaching points in a different direction: its immune activity is tied to nanodisc-mediated delivery of antigen together with CpG/adjuvant to promote immune activation. Improving lymph-node delivery of peptide antigen alone would not reasonably be expected to overcome the absence of adjuvant or convert the '603 patent peptides into an effective tolerogenic nanodisc therapy. Accordingly, the proposed combination reflects hindsight reconstruction rather than a teaching, suggestion, or reasonable expectation of success supplied by the cited art.
For at least the above reasons, there is no motivation to combine the '603 patent with Moon to arrive at the claimed invention. Applicant respectfully requests withdrawal of the rejections under 35 U.S.C. § 103.
In response to the argument that Moon does not teach or suggest the presently claimed adjuvant-free tolerogenic composition for celiac disease, the ‘603 patent teaches that adjuvant is optional, see col. 6, line 58, in particular. The ‘603 patent teaches 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 response to the argument that prior art Nexvax2 (NCT03644069, Tye-Din, J.A. et al. Lancet Gastroenterol. Hepatol., 2023, 8, 446-457, Findings) at the time of filing the instant application that the combination of instant SEQ ID NOs: 474, 475, and 476 was ineffective for achieving tolerization, it is noted that the examine claims are drawn to a composition, not a method of tolerization or a method of treating celiac disease.
Contrary to applicant’s assertion that there would have been no motivation to combine the '603 patent with Moon, Moon teaches sHDL nanoparticles can be conjugated to any antigen peptide using CSS linker, see para. [0194], [0303] or cysteine modified Ag peptide (see para. [0075]). Moon teaches compositions comprising the sHDL nanoparticle (aka nanodiscs) conjugated to peptides are also useful as desensitizing vaccines, which function to “tolerize” an individual to an environmental antigen, such as an allergen, see para. [0243] to attenuate allergic reactions in subjects exposed to allergens, see para. [0250]. The homogenous sHDL nanodiscs remain stable up to one month at 4˚C, see p. [0076].
In response to the argument that the skilled person would not have had a reasonable expectation that combining the '603 patent peptides with Moon's sHDL nanoparticle would yield the claimed adjuvant-free tolerogenic composition, one of ordinary skilled in the art would have had a reasonable expectation in conjugating the '603 patent’s immunodominant HLA-DQ2·5-restricted epitopes to Moon's sHDL nanoparticle wherein each peptide comprises an N-terminus modified with a cysteine residue bound to a linker, e.g., CSS 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 and the ‘603 patent teaches repeated administration of the peptide is expected to induce T cell energy and/or tolerance. Ongoing regular peptide administration (nanoparticle) 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). The advantages of the composition comprising sHDL nanoparticle are reduced frequency of administration as well as protection of peptides from environmental condition changes. Repeated small, fixed doses of adjuvant-free peptides, specifically immunodominant epitopes for gluten-specific CD4-positive T cells, are capable of modifying the recall immune response to gluten in HLA-DQ2·5-positive patients with coeliac disease without causing duodenal injury.
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).
For these reasons, the rejection is maintained.
Conclusion
No claim is allowed.
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 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
