Antibody-conjugated nanoparticles

JP2026102638APending Publication Date: 2026-06-23UNIV OF WASHINGTON
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Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
UNIV OF WASHINGTON
Filing Date
2026-02-26
Publication Date
2026-06-23

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Abstract

The present invention provides particles containing a polypeptide comprising an Fc-binding domain, a helix polypeptide domain, and an oligomerization domain, as well as an α-TNFRSF antibody. [Solution] A particle comprising (a) a plurality of polypeptide polymers and (b) a plurality of α-TNFRSF antibodies containing Fc domains, wherein each monomer in the polymer contains an amino acid sequence that is at least 90% identical to a specific amino acid sequence, (i) each α-TNFRSF antibody in the plurality of antibodies contains a first Fc domain and a second Fc domain, (ii) each α-TNFRSF antibody in the plurality of antibodies is (A) non-covalently bonded to one polypeptide monomer chain of the first polymer via a first Fc domain and (B) non-covalently bonded to one polypeptide monomer of the second polymer via a second Fc domain, and (iii) each polypeptide monomer chain of each polymer is non-covalently bonded to one Fc domain, and the particle contains polyhedral symmetry.
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Claims

1. (a) Multiple polypeptide polymers, and (b) Multiple α-TNFRSF (tumor necrosis factor receptor superfamily) antibodies containing an Fc domain A particle containing, Each monomer in the polymer contains an amino acid sequence that is at least 90% identical to one of the amino acid sequences of SEQ ID NOs: 1 to 9, and any residue of the amino acid sequences of SEQ ID NOs: 1 to 9 may or may not be present. (i) Each α-TNFRSF antibody in the plurality of antibodies comprises a first Fc domain and a second Fc domain, (ii) Each α-TNFRSF antibody in the plurality of antibodies is (A) non-covalently bonded to one polypeptide monomer chain of the first polymer via a first Fc domain, and (B) non-covalently bonded to one polypeptide monomer of the second polymer via a second Fc domain; and (iii) Each polypeptide monomer chain of each polymer is non-covalently bonded to one Fc domain; A particle that exhibits dihedral, tetrahedral, octahedral, or icosahedral symmetry.

2. Each monomer in a polypeptide polymer is (a) Fc binding domain, (b) Helix polypeptide domain, and (c) Oligomerized domains that associate via non-covalent interactions to form a multimer The particles according to claim 1, including the particles described in claim 1.

3. The particle according to claim 2, wherein the polymer is a dimer, trimer, tetramer, or pentamer, each having C2, C3, C4, or C5 periodic symmetry.

4. (i) The particle contains a multimer that is not a homooligomer, (ii) Each polymer in the particle is identical, or (iii) Each monomer in each polymer is identical, and each polymer is a homopolymer. The particle according to claim 1.

5. The particle according to claim 4, wherein each polymer is a homopolymer, and each homopolymer in the particle is identical.

6. Multiple polymers, (i) Sequence ID: A polypeptide trimer containing an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of 4 to 6, or (ii) A polypeptide tetramer containing an amino acid sequence that is at least 90% identical to the amino acid sequence of Sequence ID No. 7, or (iii) Sequence ID: A dimer of a polypeptide containing an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of 1 to 3, or (iv) Sequence ID: A pentamer of polypeptide containing an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of 8-9. Includes, Sequence ID: Any residue in the amino acid sequence of 1-9 may or may not be present. The particle according to claim 1.

7. The particle according to claim 1, wherein residues present at the polymer interface of a polymer of any one polypeptide from SEQ ID NO: 1 to 9, as defined in Table 2, are preserved.

8. The particle according to claim 1, wherein a residue present at any one of the Fc binding interfaces of sequence numbers 1 to 9 as defined in Table 3 is preserved.

9. (i) SEQ ID NO: A substitution to any one of the reference sequences 1 to 9 is essentially a substitution, or consists of a substitution, including a substitution at a polar residue in the reference polypeptide. (ii) Sequence ID: A substitution to any one of the reference sequences 1 to 9 consists of an essential substitution, or a substitution, including a substitution at a polar residue at a non-Gly / non-Pro residue at a loop position in the reference polypeptide, as defined in Table 4, or (iii) Sequence ID: The amino acid change from any one of the reference polypeptides 1-9 is a conservative amino acid substitution. The particle according to claim 1.

10. The particle according to claim 1, wherein the α-TNFRSF antibody targets one or more of the following: DR5, CD40, 4-1BB, and tumor necrosis factor-like apoptosis weakly inducing factor receptor (TWEAKR).

11. α-TNFRSF antibody, Sequence IDs: 19 and 20; Sequence IDs: 21 and 22; Sequence IDs: 23 and 24; Sequence IDs: 25 and 26; Sequence IDs: 27 and 28; Sequence IDs: 31 and 32; Sequence IDs: 34 and 35; Sequence IDs: 36 and 37; Sequence IDs: 38 and 39; Sequence IDs: 40 and 41; Sequence IDs: 42 and 43; Sequence IDs: 44 and 45; Sequence IDs: 44 and 46; Sequence IDs: 48 and 49; Sequence IDs: 50 and 51; Sequence IDs: 52 and 53; Sequence IDs: 54 and 55; The heavy and light chains of Rob7 / 6 as disclosed in U.S. Patent Application Publication: US20090074711; and A pair of heavy and light chains disclosed in U.S. Patent Application Publication: US2018094300, A pair of heavy and light chains selected from the group consisting of, or Sequence ID: 29; Sequence ID: 30; Sequence ID: 33; and Sequence ID: 56 A heavy chain sequence selected from the group consisting of the following: The particle according to claim 10, comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of the original.

12. The particle according to any one of claims 1 to 11, wherein multiple polymers comprise a trimer of a polypeptide having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

6.

13. The particle according to any one of claims 1 to 11, wherein multiple polymers comprise a tetramer of a polypeptide having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

7.

14. A composition comprising a plurality of particles according to any one of claims 1 to 11.

15. (i) All antibodies in the composition are identical, or (ii) The antibodies in the composition are not identical overall. The composition according to claim 14.

16. (a) a particle according to any one of claims 1 to 11, and (b) a pharmaceutically acceptable carrier, comprising a pharmaceutical composition.

17. A pharmaceutical composition for use in a method for treating a tumor in a subject requiring such treatment, wherein the pharmaceutical composition comprises the particles described in any one of claims 1 to 11 and is administered to the subject.

18. The method according to claim 17, wherein the tumor overexpresses DR5 compared to a control tumor or a threshold DR5 expression level.

19. (a) One or more polypeptides comprising an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 9, wherein any residue of the amino acid sequences of SEQ ID NOs: 1 to 9 may or may not be present, and the polypeptide is capable of (a) associating with a homopolymer and (b) binding to the constant region of an IgG antibody; and (b) α-TNFRSF antibody comprising an antibody selected from the group consisting of Lob7 / 6, lucatumumab, dasetuzumab, sericrelumab, breserumab, urerumab, utomirumab, droditumab, scTRAIL-Fc, KMTR2, 16E2, and conatumumab, A kit that includes this.

20. (a) A host cell capable of expressing one or more polypeptides containing an amino acid sequence that is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 9, wherein any residue of the amino acid sequences of SEQ ID NOs: 1 to 9 may or may not be present, and the polypeptide can (a) associate with a homopolymer and (b) bind to the constant region of an IgG antibody; and (b) Host cells capable of expressing an α-TNFRSF antibody containing an antibody selected from the group consisting of Lob7 / 6, lucatumumab, dasetuzumab, sericrelumab, breserumab, urerumab, utomirumab, droditumab, scTRAIL-Fc, KMTR2, 16E2, and conatumumab. A kit that includes this.

21. The particle according to any one of claims 1 to 11, wherein the particle, polypeptide polymer, one or more monomers, antibody, and / or dimer are covalently or noncovalently linked to one or more compounds to promote the extension of the in vivo half-life or the enhancement of stability or activity in the blood or at the injection site, and such linkage includes chemical crosslinking, PEGylation, HESylation, PASylation, and / or glycosylation.