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
Election/Restrictions
Applicant's election with traverse of group 1 in the reply filed on 1/16/2026 is acknowledged. However, applicant did not distinctly and specifically point out the supposed errors in the restriction requirement. Applicant also elect species as follows:
i) HLA-A as the MHC-H chain peptide listed in claim 3, more specifically the HLA- A*0201 sequence of SEQ ID NO:24 in claims 4 and 5,
ii) the ß2M sequence from SEQ ID NO:1,
iii) the order of elements in the\ N- to C-terminal direction of romanette (i), "the peptide epitope, the ß2M sequence, and the MHC-H polypeptide," in claim 13,
iv) the Knob-in Hole (KiH) interspecific sequence listed in claim 14,
v) IL-2 as the MOD or MOD variant listed in claim 19, and
vi) a cancer epitope as the epitope listed in claim 21.
Claims 6-9, 11, 15, 17-18, 20, 22, 24-25. 27-28, and 30-32 have been cancelled.
Claims 1-5, 10, 12-14, 16, 19, 21, 23, 26, 29, and 33-36 are pending.
Claims 2, 26, 29, and 33-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention/species, there being no allowable generic or linking claim.
Claims 1, 3-5, 10, 12-14, 16, 19, 21, and 23, drawn to a multimeric antigen-presenting polypeptide complex comprising framework polypeptide, dimerization polypeptide and one sequence MHC comprising β2M (elect SEQ ID NO: 1) and HLA-A (elect SEQ ID NO: 24), are examined on merits.
Information Disclosure Statement
The information disclosure statement (s) (IDS) submitted on 7/3/2023 are/is considered by the examiner and initialed copies/copy of the PTO-1449 are/is enclosed.
Sequence Requirement
A first office action can be performed on this application, however, this application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2). This application fails to comply with the requirements of 37 C.F.R. §§ 1.821-1.825.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification on page 45-46 [0172-174], e.g. GTLRG etc. and linker sequences are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
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 sequence identifiers, 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.
Applicant should follow the guidance for patent applications containing nucleotide sequence and/or amino acids sequence disclosure-the sequence rules in MPEM 2420-2426 and 2422.01 in particular.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings figures 11, 16-17 etc. (epitope, linker sequence) are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). 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.
Applicant is given three months from the date of the letter within which to comply with the sequence rule.
Claim Rejections - 35 USC § 112
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.
Claims 1, 3-5, 10, 12-14, 16, 19, 21, and 23 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.
The claims are broadly drawn to
A multimeric antigen-presenting polypeptide complex (MAPP) comprising:
(i) a framework polypeptide comprising from N-terminus to C-terminus a dimerization sequence and a multimerization sequence;
(ii) a dimerization polypeptide comprising a counterpart dimerization sequence complementary to the dimerization sequence of the framework polypeptide, and dimerizing therewith through covalent and/or non-covalent interactions to form a MAPP heterodimer, and
(iii) at least one presenting sequence;
wherein
(a) each presenting sequence comprises epitope, MHC Class I heavy chain ("MHC-H"), an β2M polypeptide sequences,
(b) one or both of the dimerization polypeptide and/or the framework polypeptide comprises a presenting sequence located on the N-terminal side of the framework polypeptide's dimerization sequence, or the N-terminal side of the dimerization polypeptide's counterpart dimerization sequence, and
(c) at least one of the framework polypeptide, dimerization peptide, and/or presenting sequence(s) comprises one, two, three or more independently selected MOD and/or variant MOD polypeptide sequences;
wherein neither the dimerization sequence nor the multimerization sequence of the framework polypeptide comprises an MHC-H polypeptide sequence or β2M polypeptide sequence; and
wherein the framework polypeptide, dimerization polypeptide, and/or presenting sequence optionally comprise one or more linker sequences selected independently,
wherein MHC-H is HLA-A, B…..has 90-100% sequence identity to SEQ ID NO: 24 (276 aa in length, claims 4-5),
wherein β2M has the 90-100% sequencer identity to SEQ ID NO: 1 (119 aa in length, claim 4),
wherein the MOD includes 4-1BB, IL-2, CD80….(claim 19),
wherein each of the dimerization or multmerization sequence is IgGFc constant region….CH1, IgCL, K, …, with or without disulfide bond interchain linked (claims 14,16), and
wherein the epitope is 6-12 aa comprising cancer epitope directed to a cancer associated antigen.
Thus, claims include multiple domains or variants thereof in the claimed multimeric polypeptides without structural definitions. Applicant does not reduce to practice and application does not describe the sufficient numbers of the species for the structures as claimed.
The specification first provides following teaching:
The present disclosure provides multimeric antigen-presenting polypeptide complexes (“MAPP” singular and “MAPPs” plural) that are at least heterodimeric and include at least one framework polypeptide and at least one dimerization polypeptide. Framework polypeptides comprise one or more polypeptide dimerization sequence that permits specific binding with other polypeptides (dimerization polypeptides) having a counterpart dimerization sequence thereby forming at least a heterodimer (See FIG. 1A).
The specification further states that present disclosure provides MAPPs for use in the treatment of disease and disorders including cancers.
The specification then describes that the epitope(s) linked to β2M is from cancer antigen and immunomodulatory domain (MOD) includes T cell stimulating factor such as IL-2, 4-1BB etc. and further define the sequences of β2 and HLA-A domain having the sequence of SEQ ID NO: 1 and 24 respectively, and framework is IgG Fc domain with amino acid substitution(s) (figure 11, sections by domains: epitope, MOD, MHC or HLA and frameworks throughout the specification).
However, this specification is insufficient to provide proper description for the instant claims and genus of the multimeric antigen-presenting-polypeptide (MAPP) complex without clearly defined epitopes, domains, and variants thereof specially recited in the claims and no correlation between the structures and potential functions as described. Moreover, the specification does not disclose distinguishing and identifying features of a representative number of members of the genus of which the claims are drawn, such as a correlation between the specific components of MAPP (and their specific arrangement), so that the skilled artisan could immediately envision, or recognize the specific structures and substantial number of members of the claimed genus of MAPP complex. Therefore, the specification fails to adequately describe species of an epitope, MHC domain, MOD and framework together as one multimeric polypeptide sequence or dimerized sequence as claimed. The specification fails to adequately describe at least a substantial number of members of the claimed genus of variants having at least 90% sequence identity to the wild type domain proteins that can be used or practiced to form a functional MAPP recited in the base claim.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed' ”. The courts have decided:
The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the “written description” inquiry, whatever is now claimed.
See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, paragraph 1, ``Written Description'' Requirement (66 FR 1099-1111, January 5, 2001) state, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by 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” (Id. at 1104). Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
The Guidelines further state, “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus” (Id. at 1106); accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus.
Therefore, only a MAPP with clearly defined structure/sequence of epitope and structures/sequences of frameworks, MOD, β2M domain, and MHC-H/HLA-A, but not full breadth of claimed MAPP meets the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Applicant may also refer to Written Description Guideline at USPTO website:
http://www.uspto.gov/web/patents/guides.htm
Example 9-protein variant and Example 10
Claim Rejections - 35 USC § 102/103
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries 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 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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
1. Claim(s) 1, 3-5, 10, 12, 14, 16, 19, 21, and 23 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as being unpatentable over Seidel III et al (US20200010528, published Jan 9, 2020, and effective filing Jun 2017) as evidenced by sequence alignment.
Seidel III et al (528 pub) disclose a multimeric polypeptide that is multimeric MHC polypeptide comprising class I MHC comprising MHC class I heavy chain and β2-micrglobulin (β2M, MHC light chain), wherein the human MHC is HLA-A, HLA-B, HLA-C, HLA-E or HLA-F…, and wherein multimeric MHC polypeptides also include an epitope presented by MHC/HLA. Seidel III et al (528 pub) further disclose a multimeric polypeptide including Fc portion (CH2-CH3) of IgG that is considered as framework polypeptide and one or more immunomodulatory polypeptide/domain (MOD defined by the specification on page 2) that is IL-2 (called IL-2 /synTach), 4-1BBL, PD-1, PD-L1, CD80 etc. and peptide linker(s) and disulfide bond (S-S) to link the polypeptides together as the structure shown below ([0122, 0128, 0133-135, 0171, 0438, 0440] etc.).
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148
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Seidel III et al (528 pub) also teach combining the two or more sets of multimeric polypeptides could form a multimeric antigen-resenting polypeptide complex comprising dimerization sequences and multimerization sequences and counterpart dimerization sequences as claimed in claim 1 and its dependent claims. Seidel III et al (528 pub) name the structure as T-cell modulatory polypeptide since the multimeric antigen-resenting polypeptide complex could induce specific T cell activity and response to the epitope contained antigen expressed on cells (section: T-cell Modulatory Multimeric Polypeptide: T cell MMP or synTacs or, [0121]+).
Seidel III et al (528 pub) also teach β2M in the multimerization sequence having the identical sequence as instant SEQ ID NO: 1 recited in claim 4 (elected) and teach human HLA-1 having the identical sequence as the instant SEQ ID NO: 24 (claim 5, elected), evidenced by sequence alignment below.
QY= SEQ ID NO: 1 (β2M)
US-16-489-586-95
Filing date in PALM: 2019-08-28
Sequence 95, US/16489586
Publication No. US20200010528A1
GENERAL INFORMATION
APPLICANT: Cue Biopharma, Inc.
APPLICANT: Seidel, Ronald D III
APPLICANT: Chaparro, Rodolfo J
TITLE OF INVENTION: Methods for Modulating an Immune Response
FILE REFERENCE: CUEB-108WO
CURRENT APPLICATION NUMBER: US/16/489,586
CURRENT FILING DATE: 2019-08-28
PRIOR FILING DATE: 2017-06-16
NUMBER OF SEQ ID NOS: 216
SEQ ID NO 95
LENGTH: 119
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 624; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MSRSVALAVLALLSLSGLEAIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MSRSVALAVLALLSLSGLEAIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLL 60
Qy 61 KNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM 119
QY= SEQ ID NO: 24 (HLA-A)
US-16-489-586-59
Filing date in PALM: 2019-08-28
Sequence 59, US/16489586
Publication No. US20200010528A1
APPLICANT: Cue Biopharma, Inc.
APPLICANT: Seidel, Ronald D III
APPLICANT: Chaparro, Rodolfo J
TITLE OF INVENTION: Methods for Modulating an Immune Response
FILE REFERENCE: CUEB-108WO
PRIOR FILING DATE: 2017-06-16
NUMBER OF SEQ ID NOS: 216
SEQ ID NO 59
LENGTH: 276
ORGANISM: Homo sapiens
Query Match 100.0%; Score 1520; Length 276;
Best Local Similarity 100.0%;
Matches 276; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYW 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYW 60
Qy 61 DGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDG 120
Qy 121 KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 KDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQ 180
Qy 181 RTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGT 240
Qy 241 FQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEP 276
||||||||||||||||||||||||||||||||||||
Db 241 FQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEP 276
Seidel III et al (528 pub) further disclose the epitope presented in the multimeric polypeptide is, but not limited to cancer associated antigenic peptide with 4, 5, 6, ….10, 11, 12, 13 … 20 amino acids in length [265-266]. Seidel III et al state that the present multimeric polypeptide provides a method of selectively modulating the activity of epitope-specific T cells (T-cell-MMP) in an individual for treatment [442, 449].
Thus, Seidel III et al (528 pub) teach and suggest the same multimeric antigen-presenting polypeptide complex recited in claim 1 and dependent claims thereof.
For 103 rejection:
The teaching of Seidel III (528 pub) would have been prima facie obvious to one skilled in the art. In order to provide activated antigen specific-T cell for treating the antigen associated disease in an individual, one skilled in the art would be motivated with reasonable expectation of success to form a multimeric antigen-presenting polypeptide and name it as MAPP complex having dimers and multimers of the each of the polypeptides and arrive at current invention without unexpected result.
2. Claim(s) 1, 3-5, 10, 12, 14, 16, 19, 21, and 23 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as being unpatentable over Seidel III et al (US20190062400, published Feb 28, 2019, effective filing at 2016) as evidenced by sequence alignment.
Note: Seidel III et al (Pub 400) and Seidel III et al (Pub 528) above are from the same inventor and applicants and provide same/similar teachings but different publication and filing dates.
Seidel III et al (Pub 400) disclose a T-cell modulatory multimeric polypeptide (T-cell MMP) that is multimeric MHC polypeptide comprising class I MHC comprising MHC class I heavy chain and β2-micrglobulin (β2M, MHC light chain), wherein the human MHC is HLA-A, HLA-B, HLA-C, HLA-E or HLA-F…, and wherein modulatory multimeric MHC polypeptides also include an epitope presented by MHC/HLA and Fc portion (CH2-CH3) of IgG that is considered as framework polypeptide and one or more immunomodulatory polypeptide/domain (MOD defined by the specification, page 2) that include IL-2 (called IL-2 /synTach), 4-1BBL, PD-1, PD-L1, CD80 etc. and peptide linkers and disulfide bond (S-S) to link the polypeptides together as the structure shown below ([2, 111-115, 147, 200, 236] etc. and claims 4-20 and 54+).
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Seidel III et al (400 pub) also teach combining the two or more sets of multimeric polypeptides could form a multimeric antigen-resenting polypeptide complex comprising dimerization sequences and multimerization sequences and counterpart dimerization sequences as claimed in claim 1 and its dependent claims. Seidel III et al (400pub) name the structure as T-cell modulatory polypeptide since the multimeric antigen-resenting polypeptide complex could induce specific T cell activity and response to the epitope contained antigen expressed on cells (section: T-cell Modulatory Multimeric Polypeptides: T cell MMP [0104]+).
Seidel III et al (400 pub) also teach β2M in the multimerization sequence having the identical sequence as instant SEQ ID NO: 1 recited in the instant claim 4 (elected) and human HLA-1 having the identical sequence as the instant SEQ ID NO: 24 (claim 5, elected), evidenced by sequence alignment as the same as above (see ScvUi for details)
Seidel III et al (400 pub) further disclose the epitope presented in the multimeric polypeptide is, but not limited to cancer associated antigenic peptide with 5-10 amino acids in length and cancer is CD19, CD20 etc. [119-121]. Seidel III et al state that the present multimeric polypeptide provides a method of selectively modulating the activity of epitope-specific T cells in an individual for treatment [9-10, 328-331].
Thus, Seidel III et al (400 pub) teach and suggest the same multimeric antigen-presenting polypeptide complex recited in the instant claim 1 and dependent claims thereof.
For 103 rejection:
The teaching of Seidel III (400 pub) would be obvious over the presently claim invention. In order to provide activated antigen specific-T cell for treating the antigen associated disease in an individual, one skilled in the art would be motivated with reasonable expectation of success to form and name it as a multimeric antigen-presenting polypeptide (MAPP) complex having dimers and multimers of the each of the polypeptides and arrive at current invention without unexpected result.
Double Patenting
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
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 (MPEP 9th Ed, Feb 2023).
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim not is patentably distinct from the reference claim(s) because the examined 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).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Over Patents claiming products:
Claims 1, 3-5, 10, 12, 14, 16, 19, 21, and 23 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over
claims 1-16 of U.S. Patent No. 10,927,158 (original application 16/812926);
claims 1-11 of U.S. Patent No. 11,505,591 (original application 16/089/335);
claims 1-29 of U.S. Patent No. 11,117,945 (original application 17/176777);
claims 1-22 of U.S. Patent No. 11,851,471 (original application 16473576);
claims 1-21 of U.S. Patent No. 11,370,821 (original application 17/507113);
claims 1-26 of U.S. Patent No. 11,505,588 (original application 17/749973);
claims 1-30 of U.S. Patent No. 11,739,133 (original application 17/961005);
claims 1-11 of U.S. Patent No. 11,702,461 (original application 17/909323);
claims 1-20 of U.S. Patent No. 12,152,061 (original application 18/237718);
claims 1-1-8of U.S. Patent No. 12,006,348 (original application 16/812125).
Although the conflicting claims are not identical, they are not patentably distinct from each other because all sets of claims are drawn to multimeric polypeptide, heterodimers comprising an antigenic epitope, MHC/HLA, and/or β2M linked to Fc constant region or linked to immunomodulatory domain (MOD). They may be named difference as T-cell modulatory multimeric polypeptide (TMMP, T-cell MMP) or multimeric antigen-presenting polypeptide complex (MAPP) etc, but all comprise the same domains and have function of inducing specific T cell response.
The instant claims are drawn to
A multimeric antigen-presenting polypeptide complex (MAPP) comprising:
(i) a framework polypeptide comprising from N-terminus to C-terminus a dimerization sequence and a multimerization sequence;
(ii) a dimerization polypeptide comprising a counterpart dimerization sequence complementary to the dimerization sequence of the framework polypeptide, and dimerizing therewith through covalent and/or non-covalent interactions to form a MAPP heterodimer, and
(iii) at least one presenting sequence;
wherein
(a) each presenting sequence comprises epitope, MHC Class I heavy chain ("MHC-H"), an β2M polypeptide sequences,
(b) one or both of the dimerization polypeptide and/or the framework polypeptide comprisc comprises a presenting sequence located on the N-terminal side of the framework polypeptide's dimerization sequence, or the N-terminal side of the dimerization polypeptide's counterpart dimerization sequence, and
(c) at least one of the framework polypeptide, dimerization peptide, and/or presenting sequence(s) comprises one, two, three or more independently selected MOD and/or variant MOD polypeptide sequences;
wherein neither the dimerization sequence nor the multimerization sequence of the framework polypeptide comprises an MHC-H polypeptide sequence or β2M polypeptide sequence; and
wherein the framework polypeptide, dimerization polypeptide, and/or presenting sequence optionally comprise one or more linker sequences selected independently,
wherein MHC-H is HLA-A, B…..has the sequence of SEQ ID NO: 24 (276 aa in length, claims 4-5),
wherein β2M has the sequencer of SEQ ID NO: 1 (119 aa in length, claim 4),
wherein the MOD includes 4-1BB, IL-2, CD80….(claim 19),
wherein each of the dimerization or multmerization sequence is IgGFc constant region….CH1, IgCL, K, …, with or without disulfide bond interchain linked (claims 14,16), and
wherein the epitope is 6-12 aa comprising cancer epitope directed to a cancer associated antigen.
The claims of Patent 10,927,158 are drawn to
A protein comprising two heterodimers,
wherein each heterodimer comprises:
a) a first polypeptide comprising, in order from N-terminus to C-terminus:
i) an HPV16 E7 epitope comprising amino acid sequence YMLDLQPETT (SEQ ID NO:13);
ii) a linker comprising amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO:89); and iii) a β2-microglobulin (β2M) polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:17; and
b) a second polypeptide comprising two variant IL-2 polypeptides, a class I MHC heavy chain polypeptide, and a variant immunoglobulin Fc polypeptide, wherein the second polypeptide comprises an amino acid sequence as set forth in SEQ ID NO:72,
wherein the first polypeptide and the second polypeptide of each heterodimer are covalently linked to one another via a disulfide bond between the Cys residue at amino acid 12 of the β2M polypeptide and the Cys residue at amino acid 236 of the class I MHC heavy chain polypeptide, and wherein the two heterodimers are joined to each other by one or more disulfide bonds that join the variant immunoglobulin Fc polypeptide of one heterodimer to the variant immunoglobulin Fc polypeptide of the other heterodimer,
The two heterodimers are described:
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476
734
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The claims of Patent 11,505,591 are drawn to
A multimeric polypeptide comprising:
a heterodimeric polypeptide comprising: a) a first polypeptide comprising:
i) an epitope; and
ii) a first major histocompatibility complex (MHC) class I polypeptide (β2M) microglobulin polypeptide; and
b) a second polypeptide comprising:
i) a second MHC class I polypeptide, wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide; and
ii) optionally an immunoglobulin (Ig) Fc polypeptide; and c) at least one first immunomodulatory polypeptide,
wherein the at least one first immunomodulatory polypeptide (MOD) is a CD80 polypeptide, 4-1BB, ….
wherein the first and second multimeric polypeptides having from N-C terminus and are described:
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152
300
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142
532
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408
538
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The claims of Patent 11,117,945 are drawn to
A heterodimer comprising:
a) a first polypeptide comprising:
i) a human papillomavirus epitope, wherein the epitope comprises the amino acid sequence YMLDLQPETT (SEQ ID NO:13); and
ii) a first major histocompatibility complex (MHC) polypeptide,
wherein the first MHC polypeptide is a β2-microglobulin (β2M) polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:17, and
b) a second polypeptide comprising:
i) two copies of an IL-2 polypeptide (MOD), each copy comprising an amino acid sequence set forth in SEQ ID NO:84;
iii) a second MHC polypeptide, wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide comprising an amino acid sequence as set forth in SEQ ID NO:19; and
iv) an immunoglobulin (Ig) Fc polypeptide, wherein the first polypeptide and the second polypeptide are covalently linked to one another via a disulfide bond.
wherein the two heterodimers are joined to each other by one or more disulfide bonds that join the Ig Fc polypeptide of one heterodimer to the Ig Fc polypeptide of the other heterodimer.
The heterodimers have dimerization structures which are same or similar as the figure above (see figure 1 of the patent).
The claims of Patent 11,851,471 are drawn to
A heterodimer comprising:
a) a first polypeptide comprising:
i) a peptide epitope;
ii) a first major histocompatibility complex (MHC) polypeptide, wherein the first MHC polypeptide is a beta-2 microglobulin (β2M) polypeptide; and
b) a second polypeptide comprising: i) a second MHC polypeptide, wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide; and wherein the first and/or the second polypeptide comprises one or more immunomodulatory polypeptides MOD), optionally, wherein the heterodimer comprises an immunoglobulin (Ig) Fc polypeptide or a non-Ig scaffold, wherein at least one of the one or more immunomodulatory polypeptides is a variant CD86 polypeptide comprising an amino acid sequence having at least 98% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:2
wherein:
a1) the first polypeptide comprises, in order from N-terminus to C-terminus: i) the peptide epitope; ii) an optional peptide linker; and ii) the β2M polypeptide; and b1) the second polypeptide comprises, in order from N-terminus to C-terminus: i) the one or more immunomodulatory polypeptides; ii) an optional peptide linker; iii) the MHC class I heavy chain polypeptide; iv) an optional peptide linker; and v) an Ig Fc polypeptide; or
a2) the first polypeptide comprises, in order from N-terminus to C-terminus:
i) the peptide epitope;
ii) an optional peptide linker; and
iii) the β2M polypeptide; and
2) the second polypeptide comprises, in order from N-terminus to C-terminus:
i) the MHC class I heavy chain polypeptide; and
ii) an optional peptide linker;
iii) an Ig Fc polypeptide; iv) an optional peptide linker; and
v) the one or more immunomodulatory polypeptides, wherein, when the heterodimer comprises two or more immunomodulatory polypeptides, a peptide linker may be interposed between the immunomodulatory polypeptides.
The heterodimers have dimerization structures which are same or similar as the figure above (see figure 1 of the patent).
The claims of Patent 11,370,821 are drawn to
A heterodimer comprising:
a) a first polypeptide comprising:
i) a cancer-associated epitope other than a human papillomavirus epitope; and
ii) a first major histocompatibility complex (MHC) Class I polypeptide, wherein the first MHC polypeptide is a β2-microglobulin (β2M) polypeptide comprising an amino acid sequence having at least 95% percent amino acid sequence identity to amino acids 21 to 119 of SEQ ID NO:95,
wherein the percent sequence identity is determinable by a sequence alignment performed using BLAST, and
b) a second polypeptide comprising:
i) two copies of an IL-2 polypeptide, wherein the two IL-2 polypeptides are linked by a peptide linker;
ii) a second MHC polypeptide, wherein the second MHC polypeptide is an MHC Class I HLA-A heavy chain polypeptide; and
iii) an immunoglobulin (Ig) Fc polypeptide, and wherein the heterodimer comprises a disulfide bond that covalently links a Cys residue in the β2M polypeptide to a Cys residue in the MHC class I heavy chain polypeptide,
wherein the two heterodimers are joined to each other by one or more disulfide bonds that join the Ig Fc polypeptide of one heterodimer to the Ig Fc polypeptide of the other heterodimer.
The heterodimers have dimerization structures which are same or similar as the figure above (see figure 1 of the patent).
The claims of Patent 11,505,588 are drawn to
A multimeric polypeptide comprising a heterodimer comprising:
a) a first polypeptide comprising:
i) a human papillomavirus epitope; and
ii) first class I major histocompatibility complex (MHC) polypeptide, wherein the first MHC polypeptide is a β2-microglobulin (β2M) polypeptide;
b) a second polypeptide comprising:
i) a second class I MHC polypeptide, wherein the second MHC polypeptide is an MHC Class I HLA-A heavy chain polypeptide;
ii) at least one immunomodulatory polypeptide, wherein the at least one immunomodulatory polypeptide is an IL-2 variant polypeptide that comprises an amino acid sequence having at least 98% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:44,
wherein the HPV epitope is an HPV E7 epitope,
wherein the β2M polypeptide comprises an amino acid sequence having at least 95% percent amino acid sequence identity to amino acids 21 to 119 of SEQ ID NO:95,
wherein the HLA-A heavy chain polypeptide comprises an amino acid sequence having at least 95% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:19,
wherein the multimeric polypeptide comprises two copies of the IL-2 variant polypeptide, and wherein each copy comprises the amino acid sequence of SEQ ID NO:84.
The multimeric polypeptides are same or similar as the figure above (see figure 1 of the patent).
The claims of Patent 11,739,133 are drawn to
A pharmaceutical composition comprising a homodimer of two heterodimers, wherein each heterodimer comprises:
a) a first polypeptide comprising:
i) a cancer-associated epitope other than a human papillomavirus epitope; and
ii) a first major histocompatibility complex (MHC) Class I polypeptide, wherein the first MHC polypeptide is a β2-microglobulin (β2M) polypeptide comprising an amino acid sequence having at least 95% percent amino acid sequence identity to amino acids 21 to 119 of SEQ ID NO:95, and
b) a second polypeptide comprising:
i) two copies of a variant IL-2 polypeptide, each copy comprising an amino acid sequence having at least 98% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:44, wherein amino acid 16 is other than a His and amino acid 42 is other than a Phe, wherein the two variant IL-2 polypeptides are linked by a peptide linker;
ii) a second MHC polypeptide, wherein the second MHC polypeptide is an MHC Class I heavy chain polypeptide; and
iii) an immunoglobulin (Ig) Fc polypeptide, and wherein each heterodimer comprises a disulfide bond that covalently links a Cys residue in the β2M polypeptide to a Cys residue in the MHC class I heavy chain polypeptide, and wherein the two heterodimers are joined to each other by one or more disulfide bonds that join the Ig Fc polypeptide of one heterodimer to the Ig Fc polypeptide of the other heterodimer,
wherein the MHC Class I heavy chain polypeptide in each heterodimer is an HLA-A heavy chain polypeptide.
The heterodimers have dimerization structures which are same or similar as the figure above (also see figure 1 of the patent).
The claims of Patent 111,702,461 are drawn to
A T-cell modulatory multimeric polypeptide (TMMP) comprising: at least one heterodimer comprising:
a) a first polypeptide comprising:
i) a hepatitis B virus (HBV) peptide epitope, wherein the HBV peptide has a length of at least 4 amino acids; and
ii) first major histocompatibility complex (MHC) polypeptide;
b) a second polypeptide comprising a second MHC polypeptide and an immunoglobulin (Ig) Fc polypeptide, and c) one or more immunomodulatory polypeptides that modulates a CD8+T cell that is specific for the HBV epitope, wherein the first and/or the second polypeptide comprises the immunomodulatory polypeptide (MOD), and wherein the first MHC polypeptide is β2-microglobulin (β2M) polypeptide; and wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide, wherein at least one of the one or more immunomodulatory polypeptides is a variant immunomodulatory polypeptide..
wherein MHC polypeptide comprises an amino acid sequence having at least 95% amino acid sequence identity to the HLA-A*0101, HLA-A*0201, HLA-A*0301, HLA-A*1101, HLA-A*2301….
Wherein the epitope comprises an amino acid sequence selected from the group consisting of FLPSDFFPSV, GLSRYVARLG, KLHLYSHPI, FLLSLGIHL, ALMPLYACI, SLYADSPSV, STLPETTVV, LIMPARFYPK, AIMPARFYPK, YVNVNMGLK, YVNVNMGLK, MQWNSTALHQALQDP, LLDPRVRGL, SILSKTGDPV……
wherein the two heterodimers are disulfide linked to one another by one or more disulfide bonds between the IgG1 Fc polypeptides present in each of the heterodimers.
The claims of Patent 12,152,061 are drawn to
A pharmaceutical composition comprising a homodimer of two heterodimers, wherein each heterodimer comprises:
a) a first polypeptide comprising:
i) a virus-associated peptide other than a peptide associated with a human papilloma virus; and
ii) a β2-microglobulin (β2M) polypeptide; and
b) a second polypeptide comprising:
i) two copies of a variant IL-2 polypeptide MOD), each copy comprising an amino acid sequence having at least 95% amino acid sequence identity to the amino acid sequence set forth in SEQ ID NO:44,…..
ii) a major histocompatibility complex (MHC) Class I heavy chain polypeptide; and
iii) an immunoglobulin (Ig) Fc polypeptide,
wherein the two heterodimers are joined to each other by one or more disulfide bonds that join the Ig Fc polypeptide of one heterodimer to the Ig Fc polypeptide of the other heterodimer, wherein the MHC Class I heavy chain polypeptide in each heterodimer is an HLA-A, HLA-B, or HLA-E heavy chain polypeptide, wherein the heterodimer comprises one or more independently selected peptide linkers interposed between one or more of the components of the first and second polypeptides,
wherein the first polypeptide of each heterodimer comprises, from N-terminus to C-terminus: i) the virus-associated peptide; ii) a peptide linker; iii) the β2M polypeptide, and the second polypeptide of each heterodimer comprises, from N-terminus to C-terminus: i) the first variant IL-2 polypeptide; ii) a peptide linker; iii) the second variant IL-2 polypeptide; iv) a peptide linker; v) the MHC class I heavy chain polypeptide; vi) a peptide linker; and vii) the Ig Fc polypeptide.
The heterodimers have dimerization structures which are same or similar as the figure above (see figure 1 of the patent).
The claims of Patent 12,006,348 are drawn to
T-cell modulatory multimeric polypeptide (T-Cell-MMP) comprising:
a) a first polypeptide comprising, i) a first major histocompatibility complex (MHC) polypeptide having an N-terminus and a C-terminus, wherein the first MHC polypeptide comprises a beta-2-microglobulin (β2M) polypeptide;
b) a second polypeptide having an N-terminus and a C-terminus comprising, in order from N-terminus to C-terminus,
(i) a second MHC polypeptide, wherein the second MHC polypeptide comprises a class I MHC heavy chain polypeptide comprising a binding pocket;
(ii) optionally a peptide linker; and
(iii) optionally an immunoglobulin (Ig) Fc polypeptide or a non-Ig polypeptide scaffold;
c) (i) a first polypeptide chemical conjugation site that is part of a linker attached to the first polypeptide or is within the first polypeptide, or
(ii) a second polypeptide chemical conjugation site that is part of a linker attached to the second polypeptide or is within the second polypeptide; wherein the first and second polypeptide chemical conjugation sites are sites at which a molecule comprising an epitope peptide may be covalently bound, either directly or indirectly through a linker, to the first or second polypeptide and positioned in the binding pocket of the T-Cell MMP for presentation to a cell bearing a T-cell receptor specific for the epitope presented by the epitope peptide; and d) one or more immunomodulatory polypeptides (MODs), wherein at least one of the one or more MODs is i) at the C-terminus of the first polypeptide, ii) at the N-terminus of the second polypeptide, iii) at the C-terminus of the second polypeptide, or iv) at the C-terminus of the first polypeptide and at the N-terminus of the second polypeptide; wherein each of the one or more MODs is an independently selected wild-type or variant MOD.
The T-cell modulatory multimeric polypeptides (T-Cell-MMP) recited in the claims have the same structures as described in figure 1 of the patent’ 158.
Although the claims in each of the patents above name the multimeric polypeptide complexes differently, all sets of the claims in the patents encompass the same/similar multimeric polypeptides with the same epitope and domains in heterodimers or dimerization, in which each of the multimeric polypeptide comprise:
an epitope,
an antigen-presenting polypeptide that is MHC class I heavy chain MHC-H (HLA) or MHC light chain β2M, and
polypeptides that are immunomodulatory domain (MOD) and/or framework polypeptide(s) IgFc domain or CH domains,
that are heterodimerized or multimerized by disulfide bond and further to form multimeric antigen-presenting polypeptide complex.
In addition, the sequences of β2M and MHC-H (HLA-A) have the same sequences as the instant SEQ ID NOs: 1 and 24 and the variants having at least 90% sequence identity respectively in all the patents (see ScvUi, sequence alignment for details). Therefore, the present claims and claims of the patents above are anticipated or obvious over each other.
The epitopes sequence with SEQ ID NOs set forth in the claims of patents above would result in the claimed species of the epitope, which would have smaller scope of for the claims of the patents than the present claims without specific epitope recited.
In order to increase the T cell activity by the antigen-presenting heterodimers, one skilled in the art would be motivated with reasonable expectation of success to form dimers or multimers of polypeptides to arrive at current invention.
For the processes using the multimeric polypeptides for treating a disease including a cancer claimed in the methods of the patents, a product used in a method would anticipate the same product claimed in the present invention.
Over Patents claiming methods only:
Claims 1, 3-5, 10, 12-14, 16, 19, 21, and 23 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over
claims 1-16 of U.S. Patent No. 10,927,161 (original application 16/927161);
claims 1-14 of U.S. Patent No. 11,104,712 (original application 17/180064);
claims 1-19 of U.S. Patent No. 11,479,595 (original application 16/830831);
claims 1-28 of U.S. Patent No. 11,767,355 (original application 17/961001);
claims 1-16 of U.S. Patent No. 11,958,893 (original application 17/381858);
claims 1-19 of U.S. Patent No. 11,993,641 (original application 18/227057);
claim 1 of U.S. Patent No. 12,485,184 (original application 18/511502).
Although the conflicting claims are not identical, they are not patentably distinct from each other because all sets of claims in the patent’s methods encompass multimeric polypeptides, heterodimers, which all comprise antigenic epitope, MHC/HLA, and/or β2M linked to Fc constant region or linked to immunomodulatory domain (MOD), which are the same polypeptides claimed in the present invention. A product used in a method would anticipate the same product claimed in the present invention.
The instant claims are set forth above:
The claims of Patent 10,927,161 are drawn to
A method of treating an individual having a cancer that expresses an HPV16 E7 antigen, the method comprising administering to the individual a combination of
(i) an effective amount of an immune checkpoint inhibitor that targets PD-1, and
(ii) an effective amount of a protein that is a homodimer of two multimeric polypeptides, wherein each multimeric polypeptide comprises:
a) a first polypeptide comprising from N-terminus to C-terminus:
i) an HPV16 E7 epitope comprising amino acid sequence YMLDLQPETT (SEQ ID NO:77);
ii) a linker comprising amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO:207); and iii) a β2-microglobulin (β2M) polypeptide comprising the amino acid sequence set forth in SEQ ID NO:48; and
b) a second polypeptide comprising two variant IL-2 polypeptides, a class I MHC heavy chain polypeptide, and a variant immunoglobulin Fc polypeptide, wherein the second polypeptide comprises the amino acid sequence set forth in SEQ ID NO:36,
wherein the first and second polypeptides are covalently linked to one another via a disulfide bond between the Cys residue at amino acid 12 of the β2M polypeptide and the Cys residue at amino acid 236 of the class I MHC heavy chain polypeptide, and
wherein the multimeric polypeptides are joined to each other by one or more disulfide bonds that join the variant immunoglobulin Fc polypeptide of one multimeric polypeptide to the variant immunoglobulin Fc polypeptide of the other multimeric polypeptide, and wherein the immune checkpoint inhibitor and the protein are administered at the same time or at different times.
The claims of Patent 11,104,712 are drawn to
A method of treating an individual having a cancer that expresses an HPV16 E7 antigen, the method comprising administering to the individual a combination of
(i) an effective amount of an immune checkpoint inhibitor that targets PD-1, wherein the immune checkpoint inhibitor comprises pembrolizumab, and
(ii) an effective amount of a protein that is a homodimer of two multimeric polypeptides, wherein each multimeric polypeptide comprises:
a) a first polypeptide comprising from N-terminus to C-terminus:
i) an HPV16 E7 epitope comprising amino acid sequence YMLDLQPETT (SEQ ID NO:77);
ii) a linker comprising amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO:207); and
iii) a β2-microglobulin (β2M) polypeptide comprising the amino acid sequence set forth in SEQ ID NO:48; and
b) a second polypeptide comprising:
i) two copies of an IL-2 polypeptide, each copy comprising the amino acid sequence set forth in SEQ ID NO:49;
ii) a second MHC polypeptide, wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO:50; and
iii) an immunoglobulin (Ig) Fc polypeptide, and wherein the multimeric polypeptides are joined to each other by one or more disulfide bonds that join the Ig Fc polypeptide of one multimeric polypeptide to the Ig Fc polypeptide of the other multimeric polypeptide, and wherein the immune checkpoint inhibitor and the protein are administered at the same time or at different times.
The claims of Patent 11,479,595 are drawn to
A method of treating cancer in an individual, the method comprising administering to the individual
(i) an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is an antibody that targets PD-1, and
(ii) a protein, wherein the protein comprises two heterodimers, wherein the two heterodimers have identical amino acid sequences, and wherein each heterodimer comprises:
a) a first polypeptide comprising:
i) a cancer-associated epitope other than an HPV16 cancer-associated epitope, wherein the cancer-associated epitope is a peptide having a length of from 8 amino acids to 14 amino acids; and
ii) a β2-microglobulin (β2M) polypeptide; and
b) a second polypeptide comprising:
i) two immunomodulatory polypeptides, wherein each of the two immunomodulatory polypeptides is a variant IL-2 polypeptide that comprises the amino acid sequence set forth in SEQ ID NO:49
ii) a class I major histocompatibility complex (MHC) heavy chain polypeptide; and
iii) an immunoglobulin (Ig) Fc polypeptide, wherein the two heterodimers are joined by one or more disulfide bonds between the Ig Fc polypeptides, … wherein the first polypeptide comprises a linker between the epitope and the β2M polypeptide, and the second polypeptide comprises an independently selected peptide linker between one or more of: a) the variant IL-2 polypeptide and the MHC heavy chain polypeptide; and b) the class I MHC heavy chain polypeptide and the Ig Fc polypeptide, and, c) the two variant IL-2 polypeptides.
The claims of Patent 11,767,355 are drawn to
A method of treating an individual having a cancer that expresses an HPV16 E7 antigen, the method comprising administering to the individual a combination of
(i) an effective amount of an immune checkpoint inhibitor that targets PD-1, wherein the immune checkpoint inhibitor is an anti-PD-1 antibody, and
(ii) an effective amount of a protein that is a homodimer of two multimeric polypeptides, wherein each multimeric polypeptide comprises:
a) a first polypeptide comprising from N-terminus to C-terminus:
i) an HPV16 E7 epitope comprising amino acid sequence YMLDLQPETT (SEQ ID NO:77);
ii) a linker comprising amino acid sequence GGGGSGGGGSGGGGS (SEQ ID NO:207); and
iii) a β2-microglobulin (β2M) polypeptide comprising the amino acid sequence set forth in SEQ ID NO:48; and
b) a second polypeptide comprising:
i) two copies of an IL-2 polypeptide, each copy comprising the amino acid sequence set forth in SEQ ID NO:49;
ii) a second MHC polypeptide, wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide comprising the amino acid sequence as set forth in SEQ ID NO:50; and
iii) an immunoglobulin (Ig) Fc polypeptide, and wherein the multimeric polypeptides are joined to each other by one or more disulfide bonds that join the Ig Fc polypeptide of one multimeric polypeptide to the Ig Fc polypeptide of the other multimeric polypeptide, and wherein the immune checkpoint inhibitor and the protein are administered at the same time or at different times.
The claims of Patent 11,958,893 are drawn to
A method of treating cancer in an individual, the method comprising administering to the individual
(i) an immune checkpoint inhibitor, wherein the immune checkpoint inhibitor is an antibody that targets CTLA-4, and
(ii) a composition comprising a protein, wherein the protein comprises two heterodimers, wherein each heterodimer comprises:
a) a first polypeptide comprising:
i) a cancer-associated epitope other than a human papilloma virus-16 (HPV16) cancer-associated epitope;
ii) a linker comprising the amino acid sequence set forth in any one of SEQ ID NOs: 205-209; and
iii) a β2-microglobulin (β2M) polypeptide; and
b) a second polypeptide comprising:
i) two immunomodulatory polypeptides, wherein each of the two immunomodulatory polypeptides is a variant IL-2 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:49;
ii) a major histocompatibility complex (MHC) class I heavy chain polypeptide; and
iii) an immunoglobulin (Ig) Fc polypeptide, wherein the two heterodimers are joined by one or more disulfide bonds between the Ig Fc polypeptides, wherein the immune checkpoint inhibitor and the composition comprising the protein are administered at the same time or at different times.
The claims of Patent 11,993,641 are drawn to
A method of treating an individual having a cancer that expresses a human papilloma virus-16 (HPV16) E7 antigen, the method comprising administering to the individual a combination of
(i) an effective amount of an immune checkpoint inhibitor that is an anti-PD-1 antibody, and
(ii) an effective amount of a protein that is a homodimer of two multimeric polypeptides, wherein each multimeric polypeptide comprises:
a) a first polypeptide comprising:
i) a peptide comprising an HPV16 E7 epitope; and
ii) a β2-microglobulin (β2M) polypeptide; and
b) a second polypeptide comprising:
i) first and second variant IL-2 polypeptides, wherein the first and second variant IL-2 polypeptides each have the amino acid sequence set forth in SEQ ID NO:49;
ii) a major histocompatibility complex (MHC) class I heavy chain polypeptide; and
iii) an immunoglobulin (Ig) Fc polypeptide, and wherein the two multimeric polypeptides are joined to each other by one or more disulfide bonds that join the Ig Fc polypeptide of one multimeric polypeptide to the Ig Fc polypeptide of the other multimeric polypeptide, and wherein the immune checkpoint inhibitor and the protein are administered at the same time or at different times.
The claims of Patent 12,485,184 are drawn to
A method of detecting, in a mixed population of T cells obtained from an individual, the presence of a T cell that binds a Wilms tumor-1 (WT1) epitope presented by a peptide-major histocompatibility complex (pMHC) complex, the method comprising the steps of:
A) contacting in vitro the mixed population of T cells with a homodimer comprising two heterodimers, wherein each heterodimer comprises:
a) a first polypeptide having the amino acid sequence set forth in SEQ ID NO: 423 comprising:
i) a Wilms tumor-1 (WT1) peptide;
ii) a β2-microglobulin (β2M) polypeptide; and
iii) a peptide linker between the WT1 peptide and the β2M polypeptide, wherein the peptide linker comprises a Cys residue, and
b) a second polypeptide having the amino acid sequence set forth in SEQ ID NO: 486 comprising:
i) two variant IL-2 polypeptides; ii) a major histocompatibility complex (MHC) class I heavy chain polypeptide; and
ii) an immunoglobulin (Ig) Fc polypeptide, wherein the WT1 peptide, the β2M polypeptide, and the MHC class I heavy chain polypeptide form a pMHC complex, wherein each heterodimer comprises a first disulfide bond formed between (i) the Cys residue in the peptide linker between the WT1 peptide and the β2M polypeptide, and (ii) a Cys residue in the MHC class I heavy chain polypeptide, wherein each heterodimer comprises a second disulfide bond formed between a Cys residue in the β2M polypeptide and a Cys residue in the MHC class I heavy chain polypeptide, and wherein two disulfide bonds link the Ig Fc polypeptide of one heterodimer to the Ig Fc polypeptide of the other heterodimer, and
B) detecting activation and/or proliferation of T cells comprising a T cell receptor that binds to the pMHC complex of each heterodimer.
Although the claims in each of the patents above are drawn to processes of treatment for a disease including cancer, the claims in the patents encompass the same/similar multimeric polypeptides in heterodimers or dimerization form and all comprise:
an epitope,
an antigen-presenting polypeptide that is MHC class I heavy chain MHC-H (HLA) or MHC light chain β2M, and
polypeptides including IL-2 as immunomodulatory domain (MOD) and/or framework polypeptide(s) IgFc domain or CH domains, that are dimerized or multimerized by disulfide bond to form multimeric antigen-presenting polypeptide complex.
In the above patents, the sequences of β2M and MHC-H (HLA-A) have the same sequences as the instant SEQ ID NOs: 1 and 24 respectively (see alignment in ScvUi for details).
The epitope sequence with SEQ ID NOs set forth in the claims of patents above would result in claiming a species of the epitopes, which would have smaller scope in the patented claims than the present claims without specifically defining epitope sequence.
A product used in a method would anticipate the same product claimed in the present invention.
Over Applications:
Claims 1, 3-5, 10, 12, 14, 16, 19, 21, and 23 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over
claims of copending Application No. 17/887199;
claims of copending Application No. 18676139;
claims of copending Application No. 18962550;
claims of copending Application No. 18/035731;
claims of copending Application No. 18/234640;
claims of copending Application No. 18/563567;
claims of copending Application No. 18/611323;
claims of copending Application No. 18653683;
claims of copending Application No. 18653696;
claims of copending Application No. 18768830;
claims of copending Application No. 18891753;
claims of copending Application No. 18/899926;
claims of copending Application No. 19038536.
Although the conflicting claims are not identical, they are not patentably distinct from each other because all sets of claims encompass multimeric antigen-presenting polypeptide complex comprising the same domains with the same functions.
For example:
The instant claims are set forth above
The claims of application ‘199 are drawn to
A heterodimer comprising:
a) a first polypeptide comprising:
i) a peptide having a length of from 7 to 14 amino acids; and
ii) a beta-2 microglobulin (β2M) polypeptide, and
b) a second polypeptide comprising a Class I major histocompatibility complex (MHC) heavy chain polypeptide and at least one immunomodulatory polypeptide,,
wherein the first and second polypeptides of the heterodimer together present a cancer associated epitope that can be recognized by a T-cell receptor (TCR) of a T cell, wherein the at least one immunomodulatory polypeptide is a variant CD80 polypeptide comprising an amino acid sequence having at least 95% amino acid sequence identity to the CD80 amino acid sequence set forth in SEQ ID NO:1,
wherein:
a) the first polypeptide comprises, in order from N-terminus to C-terminus
:i) the peptide;
ii) an optional linker; and
iii) the β2M polypeptide, and
b) the second polypeptide comprises, in order from N-terminus to C-terminus
:i) the at least one immunomodulatory polypeptide;
ii) an optional linker;
iii) the class I MHC heavy chain polypeptide; iv) an optional linker; and v) the Ig Fc polypeptide
c) the first polypeptide comprises, in order from N-terminus to C-terminus:
i) the peptide;
ii) an optional linker; and
iii) the β2M polypeptide, and
d) the second polypeptide comprises, in order from N-terminus to C-terminus:
i) the class I MHC heavy chain polypeptide;
ii) an optional linker;
iii) the Ig Fc polypeptide; and
iv) an optional linker; and
v) the at least one immunomodulatory polypeptide. wherein, when the heterodimer comprises two or more immunomodulatory polypeptides (MOD), one or more linkers may be interposed between the immunomodulatory polypeptides.
All sets of the claims in the applications above encompass the same/similar multimeric polypeptides in heterodimers or dimerization form and all comprise:
an epitope,
an antigen-presenting polypeptide that is MHC class I heavy chain MHC-H (HLA) or MHC light chain β2M, and
polypeptides that are immunomodulatory domain (MOD) and/or framework polypeptide(s) IgFc domain or CH domains,
that are heterodimerized or multimerized by disulfide bond to form multimeric antigen-presenting polypeptide complex.
Therefore, the present claims and claims of the patents are obvious over each other. In addition, in order to increase the T cell activity by the antigen-presenting heterodimers or multimeric polypeptides, one skilled in the art would be motivated with reasonable expectation of success to form multimers with any numbers of the polypeptides to arrive at current invention.
These are provisional obviousness-type double patenting rejections because the conflicting claims have not in fact been patented.
In looking the newly filed applications, it is noted that applicants have numerous copending applications encompassing the same or similar subject matter as the instantly claimed invention. Applicant should review the subject matter considered the same or substantially the same in all the applications and submit the appropriate information and filing Terminal Disclaimer(s).
Claim Objection
Claims 1, 3-5, 10, 12-14, 16, 19, 21, and 23 are objected to because of the following informalities:
The claims contain abbreviated terms, MOD, β2M, and contiguous aas. Although the specification provides full name for some of the terms [000, 0008, 0022], the abbreviations should be spelled out when first used in the claims. The dependent claims are included in the rejection because they all contain the same abbreviated terms in the claims they depend on.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lei Yao, whose telephone number is (571) 272-3112. The examiner can normally be reached on 8:00am-6:00pm Monday-Friday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached on (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LEI YAO/Primary Examiner, Art Unit 1642
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