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 .
DETAILED ACTION
1. 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 Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above. In the instant case, the file name is missing “.xml” at the end.
Required response – Applicant must 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.
2. Applicant’s amendments/responses filed 7/5/23 and 2/14/24 are acknowledged and have been entered. Claim 86 is independent.
3. 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.
4. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
5. Claims 86-89 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). "Compliance with the written description requirement is essentially a fact-based inquiry that will ‘necessarily vary depending on the nature of the invention claimed.’" Enzo Biochem, 323 F.3d at 963, 63 USPQ2d at 1612. An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. See MPEP 2163 I.A.
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613 (quoting the Written Description Guidelines, 66 Fed. Reg. at 1106, n. 49, stating that "if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function".). "Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function." See MPEP 2163 II.3.
Applicant has broadly claimed an antigen-presenting polypeptide (APP) comprising:
a) a first polypeptide comprising:
(i) a T1D (type 1 diabetes-associated peptide); and
(ii) a first MHC class II polypeptide, wherein the first MHC class II polypeptide is an MHC class II beta polypeptide; and
b) a second polypeptide comprising:
(i) a second class II polypeptide, wherein the second MHC class II polypeptide is an MHC class II alpha polypeptide; and
(ii) an immunoglobulin (Ig) Fc polypeptide,
wherein the first and second polypeptide of the heterodimer are covalently liked to one another via at least one disulfide bond, and wherein the APP does not include an immunomodulatory polypeptide (as is recited in instant base claim 86),and including the limitations recited in instant dependent claims 87-89, including a pharmaceutical composition comprising the APP (claim 89).
As such, the first and second polypeptides encompass any of the natural MHC class II alpha and beta chains or portions thereof as well as natural or artificial variants thereof, and the covalent linkage via at least one disulfide bond may occur at any position in either of the two MHC II polypeptides, as is enunciated below in detail.
The specification does not disclose a representative number of species of such polypeptide in the claimed composition, nor sufficient relevant identifying characteristics in the form of structure or functional characteristics coupled with a known or disclosed correlation between structure and function.
Evidentiary reference HLA Nomenclature 2023 (2 pages, 2023) teaches that in humans alone, there are 10,754 different HLA (human MHC) class II alleles (see entire reference, especially Numbers of HLA Alleles and HLA class II sections).
The instant specification discloses that the term polypeptide refers to a polymeric form of amino acids of any length, which can include coded and non-coded amino acids, chemically or biochemically modified or derivatized amino acids, and polypeptides having modified peptide backbones. The specification further discloses that as used herein a “polypeptide” refers to a protein that includes modifications, such as deletions, additions, and substitutions (generally conservative in nature as would be known to a person in the art) to the native sequence, as long as the protein maintains the desired activity (i.e., has the desired functional property, presumably in associating to form a MHC class II peptide binding site and being capable of being bound by a cognate or cross-reactive T cell). The specification discloses that these modifications can between deliberate, as through site-directed mutagenesis, or can be accidental, such as through mutations of hosts that produce the proteins, or errors due to polymerase chain reaction amplification or other recombinant DNA methods, and that references to a specific residue or number in a known polypeptide are understood to refer to the amino acid at that position in the wild-type polypeptide ([044]).
For example, the specification discloses that a DRA polypeptide (i.e., a human HLA-DR alpha chain that is essentially invariant in the peptide binding groove region and is a partner for various HLA-DR beta chains) can in some cases be a DRA1 polypeptide that can have at least 60% amino acid sequence identity with amino acid residues 26-203 of the DRA amino acid sequence depicted in Figure 6 ([00112]) or Figure 8 ([00118]), but also includes allelic variants, for example, naturally occurring allelic variants ([00113]). For example, the specification discloses that MHC class II beta chains comprise a beta 1 domain and a beta 2 domain, and the said domains can in some cases be from two different MHC class II beta chain polypeptides ([00128]). The specification discloses that in some cases, the MHC II beta chain polypeptide is a variant that comprises a non-naturally occurring Cys residue. ([00130]). The specification also discloses that in some cases, a suitable MHC class II beta chain polypeptide is a (HLA-) DRb1 polypeptide that can have at least 60% amino acid sequence identity with amino acids 30-227 of any DRb1 amino acid sequence depicted in Figure 7 ([00131]). For example, a DRb3 polypeptide includes allelic variants, such as naturally occurring allelic variants ([00141), but can also include an amino acid sequence having at least 60% amino acid sequence identity to the beta 1 and beta 2 domains disclosed at [00142] and [00143]). This disclosure for the rest of the human MHC class II polypeptides is similar in the percent identity and allelic variants.
The specification discloses that the covalent linkage of the two MHC II polypeptides is via at least one disulfide bond. In a non-limiting example, the disulfide bond may be present between a cysteine (Cys) present in the first MHC II polypeptide and a Cys present in the second MHC II polypeptide ([0070]). The specification discloses that the at least one disulfide bond provides for increased stability and/or expression of the construct (i.e., the functional property of increased stability and/or expression of the construct formed by the two polypeptides) ([0070]). The specification further discloses that generally speaking, potential locations in the heterodimer for disulfide bonds are where residues in the first and second polypeptides of the heterodimer are separated by a distance of 5 angstroms or less. Such locations represent potential locations where Cys residues, if not naturally present, can be substituted for residues that exist in the polypeptides ([0087]).
The specification further discloses high risk T1D HLA II haplotypes (Table 1 at [00166]), and that a T1D peptide is a peptide when present in an antigen-presenting polypeptide of the disclosure, presents a T1D-associated epitope capable of being bound by a TCR on the surface of a T cell (i.e., the peptide epitope has the functional property of binding to a MHC II peptide binding groove formed by the MHC II first and second polypeptides, and when so bound, has the functional property of binding to a TCR on the surface of a T cell and eliciting a T cell response) ([00190]). The specification discloses that antigens associated with T1D include for example, preproinsulin, proinsulin, insulin, insulin beta chain or alpha chain, GAD65, GAD67, IA-2, HSP65, IGRP, IA2 and ZnT8 proteins/complexes ([00191]). The specification disclose that an antigen associated with a particular autoimmune disorder is an antigen that is a target of autoantibodies and/or autoreactive T cells present in individuals with said autoimmune disorder, where such autoantibodies and/or autoreactive T cells mediate a pathological state associated with the autoimmune disorder ([00191]). The specification discloses that the length of such a T1D-associated epitope may be from about 4 amino acid residues in length to about 25 amino acid residues in length ([00190]), and that the definition of “about” encompasses a 10% deviation from the recited value ([0061]).
The specification does not disclose a representative number of such T1D peptides for the breadth of the MHC II molecules formed by the generic MHC II polypeptides recited in the APP of the instant claims. The art recognizes that the primary sequence of an amino acid sequence does not correlate with the functional properties of binding to a MHC molecule and when so bound exhibiting the functional property of binding to a TCR on a T cell and eliciting a T cell response. Neither the specification, nor the art discloses T1D-associated MHC II restricted peptides that are less than the length required to span the MHC II binding peptide binding groove (generally 8-10 amino acid residues in length depending upon the primary sequence of the peptide and the particular MHC II peptide binding groove).
The specification discloses that suitable linkers (or spacers) can be of any number of suitable lengths, including for example, from 2 to 50 amino acid residues in length ([00187]), and can for example comprise glycine and serine containing linkers ([00188]).
The specification discloses some examples of a particular Gly/Ser/Ala linker attached to an HLA-DRA1*0101 chain-Fc and a proinsulin (75-92;K88S) peptide-(G2S)3 linker-HLA-DRB1*0401 (beta chain, domains beta 1 and beta 2) with a F7C, P5C, N33C, N19C, G20C, Q156C, W153C, or Q10C mutation (Figure 18A) and testing for their levels upon recombinant production.
Given the broad definition of the first and second MHC II polypeptides (natural allelic variants, artificial variants via 60% identity and/or substitution, addition, deletion), the breadth of the position/location of the residues that are involved in the at least one disulfide bond (and including wherein one Cys residue is present in a diversity of different potential linkers), it is clear that the disclosure does not provide a representative number of species of such APP.
Therefore, it appears that the instant specification does not adequately disclose the breadth of the APP recited in the instant claims. In light of this, a skilled artisan would reasonably conclude that Applicant was not in possession of the genus of all such APPs and the pharmaceutical compositions comprising them at the time the instant application was filed.
6. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
7. Claims 86-89 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of copending Application No. 18/673,179. Although the claims at issue are not identical, they are not patentably distinct from each other because the APP recited in claims 35-60 of ‘179 is a species of that recited in the instant claims, as it comprises a first polypeptide comprising a T1D peptide epitope capable of being bound by a TCR (when bound by a class II MHC molecule), a first MHC class II polypeptide and optionally a linker that links the T1D peptide to the first MHC class II polypeptide, and a second polypeptide comprising a second MHC class II polypeptide, wherein the first and second polypeptide of the heterodimer are covalently linked to one another via at least one disulfide bond, wherein one of the polypeptides comprises an Ig Fc polypeptide optionally joined to the first or second polypeptide via a linker, and wherein the APP does not include and immunomodulatory polypeptide. The first MHC II is a beta chain polypeptide and the second MHC II polypeptide is an alpha chain polypeptide (claim 36 of ‘179). The Ig Fc polypeptide induces cell lysis through activation of CDC and/or elicits ADCC (claim 57 of ‘179). The APP comprises two heterodimers disulfide bonded to each other through their respective Ig Fc polypeptides (claim 59 of ‘179). Claim 60 of ‘179 is drawn to a composition of the said APP and a pharmaceutically acceptable excipient.
Claims 61-63 of ‘179 are drawn to one or more nucleic acids comprising nucleotide sequences encoding the said APP, one or more expression vectors thereof and a host cell genetically modified with the said one or more nucleic acids or expression vectors. Claim 64 of ‘179 is drawn to a method of reducing the number and/or activity of self-reactive T cells specific for a T1D associated epitope in an individual comprising contacting CD4+ T cells with the said APP. Claim 65 of ‘179 is drawn to a method of treating T1D in an individual comprising administering an effective amount of said APP. Claim 66 is drawn to a method of detecting a CD4+ T cell specific for a T1D-associated epitope in an individual comprising contacting the T cell with said APP. With regard to the nucleic acid and method claims of ‘179, although ‘179 is a grandchild case of the instant application, given that Applicant chose to file the ‘179 case as a separate unrelated application, not as a DIV of the instant application, and there is no restriction requirement in the instant application, the instant rejection has been set forth.
Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
8. 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.
9. 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.
10. Claims 86-89 are rejected under 35 U.S.C. 103 as being obvious over WO2019051094 A1, US2024/0034767 A1, or US 2020/0172595 A1, any one in view of US 11,339,201 and WO9604314 A1.
The applied reference has a common inventor and assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Instant independent claim 86 recites:
86. (New) An antigen-presenting polypeptide (APP) comprising: a) a first polypeptide comprising: i) a Type 1 Diabetes-associated peptide (“T1D peptide”); and li) a first major histocompatibility complex (MHC) class II polypeptide, wherein the first MHC class II polypeptide is an MHC class II B polypeptide, and b) a second polypeptide comprising: 1) a second MHC class II polypeptide, wherein the second MHC class II polypeptide is an MHC class II a polypeptide; and li) an immunoglobulin (Ig) Fc polypeptide, wherein the first and the second polypeptide of the heterodimer are covalently linked to one another via at least one disulfide bond, and wherein the APP does not include an immunomodulatory polypeptide.
WO2019051094 A1 teaches a multimeric antigen presenting polypeptide (multimeric APP) comprising first polypeptide comprising (all in order from N- to C-terminus), a first polypeptide comprising an MHC class II alpha 1/alpha 2 polypeptide (an extracellular portion of an MHC II alpha chain), and a second polypeptide comprising a peptide epitope that is recognized and bound by a TCR and an MHC class II beta 1/beta 2 polypeptide (an extracellular portion of an MHC II beta chain), and the construct also comprises an Ig Fc (e.g., [0074]), including IgG Fc (e.g., Fig. 28A), and the two polypeptide chains are covalently linked to one another, for example, by a disulfide bond ([0073]). WO2019051094 A1 teaches that a linker polypeptide present in an APP (antigen presenting polypeptide) includes a cysteine residue that can form a disulfide bond with a cysteine residue present in a second polypeptide of the APP ([00154]). WO2019051094 A1 teaches that a peptide epitope present in the APP may be relevant to T1D (type 1 diabetes, e.g., at [00162]). WO2019051094 A1 teaches that the order of the components in the polypeptides may alternatively be: in the first polypeptide, the epitope-MHC class II beta 1 domain/beta 2 domain; and the second polypeptide comprises a MHC class II alpha 1 domain/alpha 2 domain and an Ig Fc polypeptide (with an immunomodulatory domain at the N-terminus of the second polypeptide chain) (e.g., claim 2 at a5/b5). WO2019051094 A1 teaches pharmaceutical compositions comprising the multimeric APP (e.g., page 39 at lines 14-21). See entire reference.
US2024/0034767 A1 or US 2020/0172595 A1 discloses all of the teachings of WO2019051094 A1 noted above (see entire reference, e.g., [0075], [0076], [0157] for US2024/0034767 A1 or e.g., [0073]-[0075], [0154] for US 2020/0172595 A1).
WO2019051094 A1 or US2024/0034767 A1 or US 2020/0172595 A1 does not teach wherein the configuration of chains in the APP having the disulfide linked alpha and beta MHC class II chains and comprising the Ig Fc that does not comprise the immunomodulatory domain has the beta chain MHC II as the first polypeptide (i.e., the first polypeptide being the epitope-beta chain of MHC II and the second polypeptide is that of the alpha chain of MHC II linked to the Ig Fc, a configuration that is also taught by WO2019051094 A1 or by US2024/0034767 A1 for a construct having an immunomodulatory domain in addition).
WO9604314 A1 discloses that the alpha 1 and beta 1 domains of MHC class II molecules fold together to form a peptide binding groove for antigenic peptides (T cell epitope peptides). WO9604314 A1 discloses that the crystal structure of human class II HLA-DR complex (a human MHC II molecule) with an antigenic peptide bound in the peptide binding groove indicates that the N-and C- terminal ends of the bound peptide extend out of the binding groove such that the C-terminus of the peptide is proximal to the N-terminus of the beta chain. WO9604314 A1 teaches that the peptide is preferentially covalently linked to the N-terminus of the beta chain (see entire reference, especially page 2 at lines 1-9, paragraph spanning pages 3-4, page 5 at lines 1-6, Fig. 1b).
US 11,339,201 discloses a multimeric polypeptide comprising (all in order from N- to C-terminus) a heterodimer comprising: a first polypeptide comprising a peptide epitope having a length of from 4 amino acids to 25 amino acids, including a self-epitope peptide, a first MHC polypeptide; and a second polypeptide comprising a second MHC polypeptide, and optionally wherein the multimeric polypeptide comprises an Ig Fc polypeptide. The first MHC class II polypeptide is an MHC class II beta chain polypeptide (comprising beta 1 and beta 2 polypeptides, whereas the second MHC polypeptide is an MHC class II alpha chain polypeptide (comprising alpha 1 and alpha 2 polypeptides) (claims 5 and 15). Claim 15 recites wherein the multimeric polypeptide comprises a first polypeptide comprising the epitope and the first MHC class II polypeptide that is a MHC class II beta chain polypeptide, and the second polypeptide comprises a second MHC polypeptide comprising the MHC class II alpha chain polypeptide and an Ig Fc polypeptide. US 11,339,201 further discloses a composition comprising the multimeric polypeptide or homodimer thereof along with a pharmaceutically acceptable carrier and also discloses making an injectable formula (it discloses a pharmaceutical composition). US 11,339,201 discloses that the autoimmune antigen from which the self-epitope peptide derives may be relevant to type 1 diabetes. See entire reference, especially claims 1, 2 and 5-18, col. 78 at lines 4-67 through column 8, col. 34 at lines 11-12).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have configured the first polypeptide chain to be the peptide epitope-beta chain of class II MHC and the second polypeptide chain to be the alpha chain of class II MHC-Fc Ig in the APP taught by the primary art reference.
One of ordinary skill in the art would have been motivated to do this in order to take advantage of a preferential configuration for the peptide epitope. Instant dependent claim 87 is included in this rejection because the human IgG subclasses fix complement to differing degrees (i.e., they induce CDC to differing degrees, see for example Canterbury Health Laboratories, 2025, chl.co.nz/test/igg-subclasses/, 7 pages). Instant dependent claim 88 is included in this rejection because one of ordinary skill in the art was aware that the Ig Fc components can disulfide bond to each other through the cysteines present in their CH2 regions, for example as Fc regions present in IgG antibodies (see for example evidentiary reference bioatla.com/appendix/antibody-structure/, 2025, 5 pages).
11. No claim is allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
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If attempts to reach the examiner by telephone are unsuccessful, the Examiner’s supervisor, MISOOK YU can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MICHAEL SZPERKA/ Primary Examiner, Art Unit 1641