IP Library › Granted Patent US 12,371,672
Granted Patent B2
US 12,371,672 · App. 18/665,920 · Granted Jul 29, 2025

Compositions and methods for antigen targeting to CD180

Inventors: Edward Clark (Seattle, WA); Jay Wesley Chaplin (Seattle, WA)
Assignee: UNIVERSITY OF WASHINGTON
C12N7/00A61K39/12A61K39/29A61K39/385A61K47/6811A61K47/6849C07K16/2896A61K2039/55511A61K2039/55561A61K2039/6056C07K2319/40C07K2319/74C12N2770/24132C12N2770/24134C12N2770/28033Y02A50/30
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Quick Facts
Patent No.
US 12,371,672
App. No.
18/665,920
Granted
Jul 29, 2025
Kind
B2
Abstract

The present invention provides compositions of CD180 targeting molecules coupled to heterologous antigens, and their use in treating and/or limiting disease.

Claims (26)

1. A composition, comprising:

(a) a CD180 targeting molecule; and

(b) a heterologous antigen attached to the CD 180 targeting molecule.

2. The composition of claim 1 , wherein the heterologous antigen is a polypeptide antigen.

3. The composition of claim 1 , wherein the heterologous antigen is a polysaccharide, carbohydrate, or a glycolipid antigen.

4. The composition of claim 1 , wherein the heterologous antigen is an allergen.

5. The composition of claim 1 , wherein the heterologous antigen is a pathogen-specific antigen.

6. The composition of claim 5 , wherein the pathogen-specific antigen comprises an antigen selected from the group consisting of a West Nile virus antigen, a hepatitis virus antigen, and a dengue virus antigen.

7. The composition of claim 1 , wherein the CD180 targeting molecule is a CD180 antibody or antibody fragment.

8. The composition of claim 7 , wherein the CD180 antibody or antibody fragment comprises a human or animal CD180 binding domain linked to an immunoglobulin constant region (Fc) domain that has impaired binding to human or animal Fc receptor FcγRIIb and/or to human or animal complement proteins.

9. The composition of claim 8 , wherein the CD180 targeting molecule is a CD180 antibody or antibody fragment, and wherein the heterologous antigen is a polypeptide.

10. The composition of claim 1 , wherein the composition further comprises an adjuvant.

11. The composition of claim 10 , wherein the adjuvant is selected from the group consisting of a toll-like receptor 7 (TLR7) agonist and a toll-like receptor 9 (TLR9) agonist.

12. An isolated nucleic acid encoding the composition of claim 9 .

13. A nucleic acid vector comprising the isolated nucleic acid of claim 12 .

14. A recombinant host cell comprising the nucleic acid vector of claim 13 .

15. A pharmaceutical composition, comprising:

(a) the composition of claim 1 ; and

(b) a pharmaceutically acceptable carrier.

16. A method for producing antibody, comprising

(a) culturing the recombinant host cell of claim 14 under conditions suitable for expression of the nucleic-acid encoded antibody composition; and

(b) isolating the antibody composition from the cultured cells.

17. A method for treating or limiting development of a disorder, comprising administering to an individual at risk of a disorder or having a disorder, an amount effective to treat or limit development of the disorder of the composition of claim 1 .

18. The method of claim 17 , where the individual has a T-cell deficiency and/or a defect in co-stimulation between B cells and T cells.

19. The method of claim 17 , wherein the individual is a neonate or is elderly.

20. The method of claim 17 , wherein the individual has an allergy.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 20, 2024
From: CLARK, EDWARD; CHAPLIN, JAY WESLEY
To: UNIVERSITY OF WASHINGTON
Reel/Frame 067468/0739 →
Continuity (6)
Continuation 18063823 · Dec 9, 2022
Continuation 16731846 · Dec 31, 2019
Continuation 16245459 · Jan 11, 2019
Continuation 14426635
Provisional Application 61702368 · Sep 18, 2012
Related Publication 20240301364A1 · Sep 12, 2024
References Cited (78)
US 8058400B2 · Figdor et al. · 2011 [cited by applicant]
US 9260529B2 · Hayden-Ledbetter · 2016 [cited by examiner]
US 9416188B2 · Chaplin et al. · 2016 [cited by applicant]
US 10196612B1 · Patel et al. · 2019 [cited by applicant]
US 10196614B2 · Clark · 2019 [cited by examiner]
US 10563179B2 · Clark · 2020 [cited by examiner]
US 11549102B2 · Clark · 2023 [cited by examiner]
US 12018291B2 · Clark · 2024 [cited by examiner]
US 20080260751A1 · Karp · 2008 [cited by applicant]
US 20110044894A1 · Karsunsky · 2011 [cited by applicant]
US 20120020956A1 · Chaplin · 2012 [cited by applicant]
US 20120039806A1 · Lahoud · 2012 [cited by applicant]
WO 2010042863A1 · 2010 [cited by applicant]
International Search Report for PCT/US2013/059898 mailed Nov. 15, 2013. [cited by applicant]
Caminschi, et al. “Boosting antibody responses by targeting antigens to dendritic cells,” Trends in Immunology, Feb. 2012, 33(2): 71-77. [cited by applicant]
Caminschi, et al., “Enhancing immune responses by targeting antigen to DC,” European Journal of Immunology, Apr. 2009, 39(4): 931-938. [cited by applicant]
Chaplin, et al., “Anti-CD180 (RP105) activates B cells to rapidly produce polyclonal lg via a T cell and MyD88—independent pathway,” Journal of Immunology, Oct. 2011, 187(8): 4199-4209. [cited by applicant]
Chaplin, et al., “Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity maturation, and immunological memory,” The Journal of Experimental Medicine Sep. 2013, 210(10): 2135-5146. [cited by applicant]
Divanovic, et al., “negative regulation of toil-like receptor 4 signaling by the toll-like receptor homolog RP105,” Nature Immunology, Jun. 2005, 6(6): 571-578. [cited by applicant]
Alving, C.R., K.K. Peachman, M. Rao and S.G. Reed 2012. Adjuvants for human vaccines. Curr. Opin. Immunol. 24:310-315. [cited by applicant]
Aranburu, A., C. Ceccarelli, E. Giorda, R. Lasorella, G. Ballatore, and R. Carsetti. 2010. TLR ligation triggers somatic hypermutation in transitional B cells inducing the generation of lgM memory B cells. J. Immunol. 1… [cited by applicant]
Berkowska, M.A., G.J. Driessen, V. Bikos, C. Grosserichter-Wagener, K. Stamatopoulos, A. Cerutti, B. He, K. Biermann, J.F. Lange, M. van der Burg, J.J. van Dongen, and M.C. van Zelm. Human memory B cells originate from … [cited by applicant]
Borriello, F., M.P. Sethna, S.D. Boyd, A.N. Schweitzer, E.A. Tivol, D. Jacoby, T.B. Strom, E. M. Simpson, G.J. Freeman, and A.H. Sharpe. 1997. B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switc… [cited by applicant]
Bowick, G.C., and A.J. McAuley. 2011. Vaccine and adjuvant design for emerging viruses: mutations, deletions, segments and signaling. Bioeng. Bugs. 2:129-35. [cited by applicant]
Capolunghi, F., S. Cascioli, E. Giorda, M.M. Rosado, A. Plebani, C. Auriti, G. Seganti, R. Zuntini, S. Ferrari, M. Cagliuso, I. Quinti, and R. Carsetti. 2008. CpG drives human transitional B cells to terminal differenti… [cited by applicant]
Carter, R.W., C. Thompson, D.M. Reid, S.Y. Wong, and D.F. Tough. 2006. Preferential induction of CD4+ T cell responses through in vivo targeting of antigen to dendritic cell-associated C-type lectin-1. J. Immunol. 177:2… [cited by applicant]
Chan, V.W., I. Mecklenbrauker, I. Su, G. Texido, M. Leitges, R. Carsetti, C. A. Lowell, K. Rajewsky, K. Miyake, and A. Tarakhovsky. 1998. The molecular mechanism of B cell activation by Toll-like receptor protein RP-105… [cited by applicant]
Chappell, C.P., K.E. Draves, N.V. Giltiay, and E.A. Clark. 2012. Extrafollicular B cell activation by marginal zone dendritic cells drives T cell-dependent antibody responses. J. Exp. Med. 209:1825-1840. [cited by applicant]
Clark, E.A., and G. Shu. 1990. Association between IL-6 and CD40 signaling. IL-6 induces phosphorylation of CD40 receptors. J. Immunol. 145:1400-6. [cited by applicant]
Clark, E.A., G.L. Shu, B. Lüscher, K.E. Draves, J. Banchereau, J.A. Ledbetter, and M.A. Valentine. 1989. Activation of human B cells. Comparison of the signal transduced by IL-4 to four different competence signals. J. … [cited by applicant]
Defrance, T., M. Taillardet, and L. Genestier. 2011. T cell-independent B cell memory. Curr. Opin. Immunol. 23:330-6. [cited by applicant]
Denis, O., D. Latinne, F. Nisol, and H. Bazin. 1993. Resting B cells can act as antigen presenting cells in vivo and induce antibody responses. Int. Immunol. 5:71-8. [cited by applicant]
Dudziak, D., A.O. Kamphorst, G.F. Heidkamp, V.R. Buchholz, C. Trumpfheller, S. Yamazaki, C. Cheong, K. Liu, H.W. Lee, C.G. Park, R.M. Steinman, and M.C. Nussenzweig. 2007. Differential antigen processing by dendritic ce… [cited by applicant]
Fink, K., K.S. Lang, N. Manjarrez-Orduno, T. Junt, B.M. Senn, M. Holdener, S. Akira, R.M. Zinkernagel, and H. Hengartner. 2006. Early type I interferon-mediated signals on B cells specifically enhance antiviral humoral … [cited by applicant]
Finkelman, F.D., J. Ohara, D. K. Goroff, J. Smith, N. Villacreses, J. J. Mond, and W. E. Paul. 1986. Production of BSF-1 during an in vivo, T-dependent immune response. J. Immunol. 137:2878-2885. [cited by applicant]
Goins, C.L., C.P. Chappell, R. Shashidharamurthy, P. Selvaraj, and J. Jacob. 2010. Immune complex-mediated enhancement of secondary antibody responses. J. Immunol. 184:6293-8. [cited by applicant]
Han, J.H., S. Akira, K. Calame, B. Beutler, E. Selsing E, and T. Imanishi-Kari. 2007. Class switch recombination and somatic hypermutation in early mouse B cells are mediated by B cell and Toll-like receptors. Immunity.… [cited by applicant]
He, B., et al., 2010. The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. Nat. Immunol. 11:836-845. [cited by applicant]
Hebeis, B.J., E. Vigorito, and M. Turner. 2004. The p110delta subunit of phosphoinositide 3-kinase is required for the lipopolysaccharide response of mouse B cells. Biochem. Soc. Trans. 32:789-791. [cited by applicant]
Hebeis, B.J., E. Vigorito, D. Kovesdi, and M. Turner. 2005. Vav proteins are required for B-lymphocyte responses to LPS. Blood. 106:635-640. [cited by applicant]
Herzenberg, L.A., S. J. Black, T. Tokuhisa, and L. A. Herzenberg. 1980. Memory B cells at successive stages of differentiation. Affinity maturation and the role of lgD receptors. J. Exp. Med. 151:1071-1087. [cited by applicant]
Kaji, T., A. Ishige, M. Hikida, J. Taka, A, Hijikata, M. Kubo, T. Nagashima, Y. Takahashi, T. Kurosaki, M. Okada, O. Ohara, K. Rajewsky, and T. Takamori. 2012. Distinct cellular pathways select germline-encoded and soma… [cited by applicant]
Kawabe, T., T. Naka, K. Yoshida, T. Tanaka, H. Fujiwara, S. Suematsu, N. Yoshida, T. Kishimoto, and H. Kikutani. 1994. The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal ce… [cited by applicant]
Kawamura, H., and J.A. Berzofsky. 1986. Enhancement of antigenic potency in vitro and immunogenicity in vivo by coupling the antigen to anti-immunoglobulin. J. Immunol. 136:58-65. [cited by applicant]
Kovesdi, D., K. Paszty, A. Enyedi, E. Kiss, J. Matko, K. Ludanyi, E. Rajnavolgyi, and G. Sarmay. 2004. Antigen receptor-mediated signaling pathways in transitional immature B cells. Cell Signal. 16:881-9. [cited by applicant]
Kuraoka, M., D. Liao, K. Yang, S.D. Allgood, M.C. Levesque, G. Kelsoe, and Y. Ueda. 2009. Activation-induced cytidine deaminase expression and activity in the absence of germinal centers: insights into hyper-lgM syndrom… [cited by applicant]
Kuraoka, M., L. McWilliams, and G. Kelsoe. 2011. AID expression during B-cell development: searching for answers. Immunol. Res. 49:3-13. [cited by applicant]
Caminschi. 2011. Targeting antigen to mouse dendritic cells via Clec9A induces potent CD4 T cell responses biased toward a follicular helper phenotype. J. Immunol. 187:842-50. [cited by applicant]
Le Bon, A., C. Thompson, E. Kamphuis, V. Durand, C. Rossmann, U. Kalinke, and D.F. Tough. 2006. Cutting edge: enhancement of antibody responses through direct stimulation of B and T cells by type I IFN. J. Immunol. 176:… [cited by applicant]
Levine MM. 2011. “Ideal” vaccines for resource poor settings. Vaccine. 29 Suppl 4:D116-25. Mao, C., L. Jiang, M. Melo-Jorge, M. Puthenveetil, X. Zhang, M.C. Carrol, and T. Imanishi-Kari. 2004. T cell-independent somatic… [cited by applicant]
Markowitz, J.S., P.R. Rogers, M.J. Grusby, D.C. Parker, and L.H. Glimcher. 1993. B lymphocyte development and activation independent of MHC class II expression. J. Immunol. 150:1223-33. [cited by applicant]
Miller, M.A., and M.H. Rathore. 2012. Immunization in special populations. Adv. Pediatr. 59:95-136. [cited by applicant]
Miyake, K., Y. Yamashita, Y. Hitoshi, K. Takatsu, and M. Kimoto. 1994. Murine B cell proliferation and protection from apoptosis with an antibody against a 105-kD molecule: unresponsiveness of X-linked immunodeficient B… [cited by applicant]
Miyake, K., Y. Yamashita, M. Ogata, T. Sudo, and M. Kimoto. 1995. RP105, a novel B cell surface molecule implicated in B cell activation, is a member of the leucine-rich repeat protein family. J. Immunol. 154:3333-3340. [cited by applicant]
Nagai, Y., T. Kobayashi, Y. Motoi, Y. Ishiguro, S. Akashi, S. Saitoh, Y. Kusumoto, T. Kaisho, S. Akira, M. Matsumoto, K. Takatsu, and K. Miyake. 2005. The radioprotective 105/MD-1 complex links TLR2 and TLR4/MD-2 in ant… [cited by applicant]
Rappuoli, R., C.W. Mandl, S. Black, and E. De Gregorio. 2011. Vaccines for the twenty-first century society. Nat. Rev. Immunol. 11:865-72. [cited by applicant]
Rickert, R.C., J. Jellusova, and A.V. Miletic. 2011. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol. Rev. 244:115-33. [cited by applicant]
Sancho, D., and C. Reis e Sousa. 2012. Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu. Rev. Immunol. 30:491-529. [cited by applicant]
Sasaki, Y., S. Casola, J. L. Kutok, K. Rajewsky, and M. Shmidt-Supprian. 2004. TNF family member B cell-activating factor (BAFF) receptor-dependent and —independent roles for BAFF in B cell physiology. J. Immunol. 173:2… [cited by applicant]
Shih, T. A., M. Roederer, and M. C. Nussenzweig. 2002. Role of antigen receptor affinity in T cell-independent antibody responses in vivo. Nat. Immunol. 3:399-406. [cited by applicant]
Snider, D.P.. and D.M. Segal. 1989. Efficiency of antigen presentation after antigen targeting to surface lgD, lgM, MHC II, Fc gamma RII, and B220 molecules on murine splenic B cells. J. Immunol. 143:59-65. [cited by applicant]
Taylor, J.J., M.K. Jenkins, and KA. Pape. 2012. Heterogeneity in the differentiation and function of memory B cells. Trends Immunol. 33:590-7. [cited by applicant]
Ueda, Y., D. Liao, K. Yang, A. Patel, and G. Kelsoe. 2007. T-independent activation-induced cytidine deaminase expression, class-switch recombination, and antibody production by immature/transitional 1 B cells. J. Immun… [cited by applicant]
Valentine, M.A., E. A. Clark, G. L. Shu, N.A. Norris, and J.A. Ledbetter. 1988. Antibody to a novel 95-kDa surface glycoprotein on human B cells induces calcium mobilization and B cell activation. J. Immunol. 140:4071-4… [cited by applicant]
Weir, D.M. , L. A. Herzenberg, C. Blackwell, and L. A. Herzenberg. 1986. Handbook of Experimental Immunology. 1:31.6-31.7. [cited by applicant]
Weller, S., A. Faili, C. Garcia, M.C. Braun, F.F. Le Deist, G.G. de Sainte Basile, O. Hermine, A. Fischer, C.A. Reynaud, and J.C. Weill. 2001. CD40-CD40L independent lg gene hypermutation suggests a second B cell divers… [cited by applicant]
Yazawa, N., M. Fujimoto, S. Sato, K. Miyake, N. Asano, Y. Nagai, O. Takeuchi, K. Takeda, H. Okochi, S. Akira, T.F. Tedder, and K. Tamaki. 2003. CD19 regulates innate immunity by the Toll-like receptor RP105 signaling in… [cited by applicant]
Zhang, J., Y.J. Liu, I.C. MacLennan, D. Gray, and P.L. Lane. 1988. B cell memory to thymus-independent antigens type 1 and type 2: the role of lipopolysaccharide in B memory induction. Europ. J. Immunol. 18:1417-24. [cited by applicant]
Zuckerman and Zuckerman, “Mutations of the surface protein of hepatitis B virus,” Antiviral Res 60:75-78, 2003. [cited by applicant]
Peterson, et al., “Structure of hepatitis B surface antigen. Correlation of subtype with amino acid sequence and location of the carbohydrate moiety,” J. Biol. Chem 257:10414-10420, 1982. [cited by applicant]
Charnay et al. “Localization on the viral genome and nucleotide sequence of the gene coding for the two major polypeptides of the hepatitis B surface antigen (HBs Ag),” Nucleic Acids Res 7:335-346, 1979. [cited by applicant]
Grakoui, et al. “Expression and identification of hepatitis C virus polyprotein cleavage products,” J. Virol 67:1385, 1993. [cited by applicant]
Choo, et al. “Genetic organization and diversity of the hepatitis C virus,” PNAS 88:2451-2458, 1991. [cited by applicant]
Huse et al., “Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda,” Science 246:1275-1281 (1989). [cited by applicant]
Ward et al., “Binding activities of a repertoire of single immunoglobulin variable domains secreted from [cited by applicant]
Vaughan et al., “Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library,” Nature Biotech. 14:309-314 (1996). [cited by applicant]
Mao, et al., “T cell-Independent Somatic Hypermutation in Murine B cells with an Immature Phenotype,” Feb. 2004, Immunity, 20:133-144. [cited by applicant]
Miura et al. RP105 is associated with MD-1 and transmits an activation signal in human B cells Blood (1998) vol. 92 (8), pp. 2815-2822. [cited by applicant]