IP Library Granted Patent US 12,383,609
Granted Patent B2
US 12,383,609 · App. 16/606,207 · Granted Aug 12, 2025

Plasmodium sporozoite NPDP peptides as vaccine and target novel malaria vaccines and antibodies binding to

Inventors: Antonio Lanzavecchia (Porza, CH); Joshua Hoong Yu Tan (Shah Alam, MY); Claudia Daubenberger (Mülheim, DE); Brandon Wilder (Seattle, WA)
Assignees: Institute for Research in Biomedicine; Seattle Children's Hospital; Schweizerisches Tropen-und Public Health-Institut
A61K39/015A61P33/06C07K16/205A61K2039/505
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,383,609
App. No.
16/606,207
Granted
Aug 12, 2025
Kind
B2
Abstract

The present invention provides a fragment of plasmodium circumsporozoite protein according to SEQ ID NO: 1, for example for use in a malaria vaccine. The present invention also provides nucleic acids encoding a fragment of plasmodium circumsporozoite protein according to SEQ ID NO: 1, compositions comprising a fragment of plasmodium circumsporozoite protein according to SEQ ID NO: 1 and antibodies binding to a fragment of plasmodium circumsporozoite protein according to SEQ ID NO: 1. The antibodies according to the present invention bind specifically to P. falciparum sporozoites and may be used in the treatment and/or prevention of malaria.

Claims (29)

1. A recombinant nucleic acid molecule comprising:

(i) a polynucleotide encoding an antibody, or an antigen-binding fragment thereof, that is capable of binding to a Plasmodium falciparum sporozoite, wherein the antibody, or the antigen-binding fragment thereof, comprises:

a heavy chain variable region (VH) comprising a CDRH1, a CDRH2, and a CDRH3, the heavy chain variable region (VH) having an amino acid sequence, the amino acid sequence consisting of SEQ ID NO: 248;

a light chain variable region (VL) comprising a CDRL1, a CDRL2, and a CDRL3, the light chain variable region (VL) having an amino acid sequence, the amino acid sequence consisting of SEQ ID NO: 249;

an IgG1 Fc moiety comprising:

a heavy chain amino acid sequence, wherein the heavy chain amino acid sequence is according to SEQ ID NO: 313; and

a light chain amino acid sequence, wherein the light chain amino acid sequence is according to SEQ ID NO: 314 or 315; and

(ii) a promoter sequence.

2. A vector comprising the recombinant nucleic acid molecule according to claim 1 .

3. The vector of claim 2 , which is an expression vector, a cloning vector, or a transfer vector.

4. A cell comprising a vector according to claim 2 .

5. The cell according to claim 4 , wherein the cell comprises a eukaryotic cell.

6. The cell according to claim 5 , wherein the cell comprises a CHO cell, a NS0 cell, a PER.C6 cell, a HEK293T cell, a HKB-11 cell, a myeloma cell, a hybridoma cell, a yeast cell, a plant cell, a human liver cell, a human B cell, or a human plasma cell.

7. A pharmaceutical composition comprising:

a recombinant nucleic acid molecule according to claim 1 , and a pharmaceutically acceptable excipient, diluent, or carrier.

8. The recombinant nucleic acid molecule according to claim 1 , comprising mRNA.

9. The recombinant nucleic acid molecule of claim 1 , in which the recombinant nucleic acid molecule is codon-optimized for expression in a CHO cell, a NS0 cell, a PER.C6 cell, a HEK293T cell, a HKB-11 cell, a myeloma cell, a hybridoma cell, a yeast cell, a plant cell, a human liver cell, a human B cell, or a human plasma cell.

10. The recombinant nucleic acid of claim 1 , wherein the light chain amino acid sequence of the IgG1 Fc moiety is according to SEQ ID NO: 314.

11. The recombinant nucleic acid of claim 1 , wherein the light chain amino acid sequence of the IgG1 Fc moiety is according to SEQ ID NO: 315.

12. The recombinant nucleic acid molecule according to claim 1 , wherein the polynucleotide comprises a sequence consisting of SEQ ID NO: 256.

13. The recombinant nucleic acid molecule according to claim 1 , wherein the polynucleotide comprises a sequence consisting of SEQ ID NO: 257.

14. The recombinant nucleic acid molecule according to claim 1 , wherein polynucleotide comprises a sequence consisting of SEQ ID NO: 256 and a sequence consisting of SEQ ID NO: 257.

15. The recombinant nucleic acid molecule according to claim 1 , wherein the polynucleotide comprises a sequence consisting of SEQ ID NO: 316.

16. The recombinant nucleic acid molecule according to claim 1 , wherein the polynucleotide comprises a sequence consisting of SEQ ID NO: 318 that encodes the light chain amino acid sequence of the IgG1 Fc moiety.

17. The recombinant nucleic acid molecule according to claim 1 , wherein the polynucleotide comprises a sequence consisting of SEQ ID NO: 316 and a sequence consisting of SEQ ID NO: 318.

18. The recombinant nucleic acid molecule according to claim 1 , wherein the polynucleotide comprises a sequence consisting of SEQ ID NO: 256 and a sequence consisting of SEQ ID NO: 316.

19. The recombinant nucleic acid molecule according to claim 1 , wherein the polynucleotide comprises a sequence consisting of SEQ ID NO: 257 and a sequence consisting of SEQ ID NO: 318.

20. The recombinant nucleic acid molecule according to claim 1 , wherein the polynucleotide comprises a sequence consisting of SEQ ID NO: 256, a sequence consisting of SEQ ID NO: 257, and a sequence consisting of SEQ ID NO: 316.

21. The recombinant nucleic acid molecule according to claim 1 , wherein the polynucleotide comprises a sequence consisting of SEQ ID NO: 256, a sequence consisting of SEQ ID NO: 257, a sequence consisting of SEQ ID NO: 316, and a sequence consisting of SEQ ID NO: 318.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 6, 2025
From: LANZAVECCHIA, ANTONIO; TAN, JOSHUA HOONG YU
To: INSTITUTE FOR RESEARCH IN BIOMEDICINE
Reel/Frame 071350/0501 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 6, 2025
From: WILDER, BRANDON
To: SEATTLE CHILDREN'S HOSPITAL D/B/A SEATTLE CHILDREN'S RESEARCH INSTITUTE
Reel/Frame 071350/0518 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 6, 2025
From: DAUBENBERGER, CLAUDIA
To: SCHWEIZERISCHES TROPEN- UND PUBLIC HEALTH-INSTITUT
Reel/Frame 071350/0531 →
CONFIRMATORY LICENSE Recorded Sep 8, 2023
From: SEATTLE CHILDREN'S HOSPITAL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 064852/0046 →
Continuity (2)
Provisional Application 62487266 · Apr 19, 2017
Related Publication 20200093909A1 · Mar 26, 2020
References Cited (131)
US 4436727A · Ribi · 1984 [cited by applicant]
US 4866034A · Ribi · 1989 [cited by applicant]
US 4877611A · Cantrell · 1989 [cited by applicant]
US 4912094A · Myers et al. · 1990 [cited by applicant]
US 5057540A · Kensil et al. · 1991 [cited by applicant]
US 6005099A · Davies et al. · 1999 [cited by applicant]
US 6303347B1 · Johnson et al. · 2001 [cited by applicant]
US 6764840B2 · Johnson et al. · 2004 [cited by applicant]
US 8258268B2 · Wu et al. · 2012 [cited by applicant]
US 9181349B2 · Baurin et al. · 2015 [cited by applicant]
US 9676857B2 · Dimitrov et al. · 2017 [cited by applicant]
US 20030119733A1 · Cerami et al. · 2003 [cited by applicant]
US 20050163783A1 · Braslawsky et al. · 2005 [cited by applicant]
US 20090017055A1 · Duffy et al. · 2009 [cited by applicant]
US 20090075404A1 · Matsunami · 2009 [cited by applicant]
US 20160176955A1 · Gutierrez et al. · 2016 [cited by applicant]
US 20170035871A1 · Ueno et al. · 2017 [cited by applicant]
US 20180362628A1 · Liang · 2018 [cited by examiner]
CN 101190946A · 2008 [cited by applicant]
EP 0109942B1 · 1991 [cited by applicant]
EP 0362279B1 · 1995 [cited by applicant]
EP 0729473B1 · 2000 [cited by applicant]
WO 9421292A1 · 1994 [cited by applicant]
WO 9509917A1 · 1995 [cited by applicant]
WO 9514026A1 · 1995 [cited by applicant]
WO 9611711A1 · 1996 [cited by applicant]
WO 9633739A1 · 1996 [cited by applicant]
WO 9850399A1 · 1998 [cited by applicant]
WO 9964301A1 · 1999 [cited by applicant]
WO 0000462A1 · 2000 [cited by applicant]
WO 0146127A1 · 2001 [cited by applicant]
WO 03011223A2 · 2003 [cited by applicant]
WO 03043572A2 · 2003 [cited by applicant]
WO 03099195A2 · 2003 [cited by applicant]
WO 2008143954A2 · 2008 [cited by applicant]
WO 2009075404A1 · 2009 [cited by applicant]
WO 2009099961A2 · 2009 [cited by applicant]
WO 2010112193A1 · 2010 [cited by applicant]
WO 2010115589A1 · 2010 [cited by applicant]
WO 2012051097A1 · 2012 [cited by applicant]
WO 2012131555A2 · 2012 [cited by applicant]
WO 2014028644A1 · 2014 [cited by applicant]
WO 2016087416A1 · 2016 [cited by applicant]
WO WO2017163049A1 · 2017 [cited by examiner]
WO 2017193032A2 · 2017 [cited by applicant]
Skolnick et al. (Trends in Biotechnology 18: 34-39, 2000). [cited by examiner]
Greenspan et al. (Nature Biotechnology 7: 936-937, 1999). [cited by examiner]
Giusti et al. (Proc. Natl. Acad. Sci. USA. May 1987; 84 (9): 2926-2930). [cited by examiner]
Winkler et al (J. Imm., 265:4505-4514, 2000). [cited by examiner]
Sela-Culang et al. (Frontiers in Immunology, 2013 vol. 4, article 302, pp. 1-13). [cited by examiner]
Tan et al. (Nature Medicine vol. 24 No. 4, pp. 401-407). (Year: 2018). [cited by examiner]
Foquet et al. (Journal of Clinical Investigation, vol. 124 No. 1, pp. 140-144). Jan. 2014. [cited by examiner]
Chien et al. (Proc. Natl. Acad. Sci. USA. Jul. 1989; 86 (14): 5532-5536). [cited by examiner]
Caldas et al. (Mol. Immunol. May 2003; 39 (15): 941-952). [cited by examiner]
Casadevall et al. (PNAS vol. 109 No. 31, pp. 12272-12273). Jul. 31, 2012. [cited by examiner]
Charoenvit et al., “Development of Two Monoclonal Antibodies against [cited by applicant]
Clement et al., “Validation of an enzyme-linked immunosorbent assay for the quantification of human IgG directed against the repeat region of the circumsporozoite protein of the parasite [cited by applicant]
Foquet et al., “Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent [cited by applicant]
International Search Report and Written Opinion, dated Dec. 3, 2018, for International Application No. PCT/EP2018/060113, 21 pages. [cited by applicant]
López et al., “Immunogenicity of Synthetic Peptides Corresponding to the Nonrepeat Regions of the [cited by applicant]
Peng et al., “Breadth of humoral response and antigenic targets of sporozoite-inhibitory antibodies associated with sterile protection induced by controlled human malaria infection,” [cited by applicant]
Swearingen et al., “Interrogating the [cited by applicant]
Wilson et al., “ Recognition of phage-expressed peptides containing Asx-Pro sequences by monoclonal antibodies produced against [cited by applicant]
Young et al., “Expression of [cited by applicant]
“Extract from the Clinical Evaluation Report for blinatumomab,” AusPAR Attachment 2, Australian Government, Department of Health, Therapeutic Good Administration, 2018. [cited by applicant]
Ahmad et al., “scFv Antibody: Principles and Clinical Application,” [cited by applicant]
Beiboer et al., “Guided Selection of a Pan Carcinoma Specific Antibody Reveals Similar Binding Characteristics yet Structural Divergence Between the Original Murine Antibody and its Human Equivalent,” [cited by applicant]
Brinkmann et al., “The making of bispecific antibodies,” [cited by applicant]
Du et al. “Engineering Bifunctional Antibodies with Constant Region Fusion Architectures” [cited by applicant]
Giudicelli et al., “IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin ant T cell receptor genes” [cited by applicant]
Golay et al. “Design and Validation of a Novel Generic Platform for the Production of Tetravalent IgG1-like Bispecific Antibodies”, [cited by applicant]
Janeway's Immunobiology (Murphy, Kenneth and Weaver, Casey, Janeway's Immunobiology, 9th Ed. 2017, Garland Science, pp. 140-148 and 415. [cited by applicant]
Klimka et al., “Human anti-CD30 recombinant antibodies by guided phage antibody selection using cell panning,” [cited by applicant]
Muda et al., “Therapeutic assessment of SEED: a new engineered antibody platform designed to generate mono- and bispecific antibodies”, [cited by applicant]
Product Package Insert, ABECMA® (idecabtagene vicleucel), suspension for intravenous infusion, 2021. [cited by applicant]
Product Package Insert, BLINCYTO® (blinatumomab) for injection for intravenous use, 2021. [cited by applicant]
Product Package Insert, BREYANZI® (lisocabtagene maraleucel) suspension for intravenous infusion, 2021. [cited by applicant]
Product Package Insert, KYMRIAH® (tisagenlecleucel) suspension for intravenous infusion, 2021. [cited by applicant]
Product Package Insert, TECARTUS™ (brexucabtagene autoleucel) suspension for intravenous infusion, 2021. [cited by applicant]
Product Package Insert, YESCARTA® (axicabtagene ciloleucel) suspension for intravenous infusion, 2021. [cited by applicant]
Rader et al. “A phage display approach for rapid antibody humanization: Designed combinatorial V gene libraries,” [cited by applicant]
Tudor et al. “Isotype modulates epitope specificity, affinity, and antiviral activities of anti-HIV-1 human broadly neutralizing 2F5 antibody,” [cited by applicant]
Wozniak-Knopp et al., “An antibody with Fab-constant domains exchanged for a pair of CH3 domains”, [cited by applicant]
Wu et al., “Blinatumomab: a bispecific T cell engage (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia,” [cited by applicant]
ASTMH 63rd Annual Meeting, Nov. 2-6, 2014, pp. 491, 1607. [cited by applicant]
Armour et al., “Recombinant human IgG molecules lacking Fcγ receptor I binding and monocyte triggering activities,” [cited by applicant]
Baker et al., “Structures of bovine and human papillomaviruses: Analysis by cryoelectron microscopy and three-dimensional image reconstruction,” [cited by applicant]
Birkholz et al., “Targeting of DEC-205 on human dendritic cells results in efficient MHC class II-restricted antigen presentation,” [cited by applicant]
Burton, “Immunoglobulin G: Functional sites,” [cited by applicant]
Capel et al., “Heterogeneity of human IgG Fc receptors,” [cited by applicant]
Casal, “Use of parvovirus-like particles for vaccination and induction of multiple immune responses,” [cited by applicant]
Chu et al., “Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcγIIb with Fc-engineered antibodies,” [cited by applicant]
Coppi et al., “The [cited by applicant]
Crompton et al., “Malaria Immunity in Man and Mosquito: Insights into Unsolved Mysteries of a Deadly Infectious Disease,” [cited by applicant]
De Haas et al., “Fcγ receptors of phagocytes,” [cited by applicant]
Duncan et al., “The binding site for Clq and IgG,” [cited by applicant]
Flower, “Designing immunogenic peptides,” [cited by applicant]
Ganesan et al., “FcγRIIb on liver sinusoidal endothelium clears small immune complexes,” [cited by applicant]
Gessner et al., “The IgG Fc receptor family,” [cited by applicant]
Goldmann et al., “Molecular Cloning and Expression of Major Structural Protein VP1 of the Human Polyomavirus JC Virus: Formation of Virus-Like Particles Useful for Immunological and Therapeutic Studies,” [cited by applicant]
Hagensee et al., “Three-Dimensional Structure of Vaccinia Virus-Produced Human Papillomavirus Type 1 Capsids,” [cited by applicant]
Hurtado et al., “Identification of Domains in Canine Parvovirus VP2 Essential for the Assembly of Virus-Like Particles,” [cited by applicant]
Hutten et al., “CLEC12A-Mediated Antigen Uptake and Cross-Presentation by Human Dendritic Cell Subsets Efficiently Boost Tumor-Reactive T Cell Responses,” [cited by applicant]
Huysamen et al., “CLEC9A Is a Novel Activation C-type Lectin-like Receptor Expressed on BDCA3 [cited by applicant]
Izard et al., “Principles of quasi-equivalence and Euclidean geometry govern the assembly of cubic and dodecahedral cores of pyruvate dehydrogenase complexes,” [cited by applicant]
Jaoudé et al., “Role of the Antigenic Loop of the Hepatitis B Virus Envelope Proteins in Infectivity of Hepatitis Delta Virus,” [cited by applicant]
Jiang et al., “Heterotypic protection from rotavirus infection in mice vaccinated with virus-like particles,” [cited by applicant]
Kanekiyo et al., “Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies,” [cited by applicant]
Kang et al., “Development of HIV/AIDS Vaccine Using Chimeric gag-env Virus-Like Particles,” [cited by applicant]
Li et al., “Expression and Self-Assembly of Empty Virus-Like Particles of Hepatitis E Virus,” [cited by applicant]
Lohcharoenkal et al., “Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy,” [cited by applicant]
Menard, “The journey of the malaria sporozite through its hosts: two parasite proteins lead the way,” [cited by applicant]
Notka et al., “Construction and Characterization of Recombinant VLPs and Semliki-Forest Virus live Vectors for Comparative Evaluation in the SHIV Monkey Model,” [cited by applicant]
Ravetch et al., “Fc Receptors,” [cited by applicant]
Salisse et al., “A Functional Essential to Viral Entry Underlies the Hepatitis B Virus “a” Determinant,” [cited by applicant]
Schneider-Ohrum et al., “Virus-like particles for antigen delivery at mucosal surfaces,” [cited by applicant]
Schreibelt et al., “The C-type lectin receptor CLEC9A mediates antigen uptake and cross- presentation by human blood BDCA3+ myeloid dendritic cells,” [cited by applicant]
Shields et al., “High Resolution Mapping of the Binding Site on Human IgGI for FcγRI, FcγRII, FcγRIII, and FcRn and Design of IgGI Variants with Improved Binding to the FcγR,” [cited by applicant]
Sinnis et al., “Sporozoite antigens: biology and immunology of the circumsporozoite protein and thrombospondin-related anonymous protein,” [cited by applicant]
Sutter et al., “Structural basis of enzyme encapsulation into a bacterial nanocompartment,” [cited by applicant]
Urich et al., “X-ray Structure of a Self-Compartmentalizing Sulfur Cycle Metalloenyzme,” [cited by applicant]
Van de Winkel et al., “Biology of Human Immunoglobulin G Fc Receptors,” [cited by applicant]
Vicente et al., “Large-scale production and purification of VLP-based vaccines,” [cited by applicant]
Ward et al., “The effector functions of immunoglobulins: implications for therapy,” [cited by applicant]
Wines et al., “The IgG Fc Contains Distinct Fc Receptor (FcR) Binding Sites: The Leukocyte Receptors FcγRI and FcγRIIa Bind to a Region in the Fc Distinct from That Recognized by Neonatal FcR and Protein A,” [cited by applicant]
Wu, Jingjing, “Blinatumomab: a bispecific T cell engage (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia,” [cited by applicant]
Zhang et al., “Self-Assembly in the Ferritin Nano-Cage Protein Superfamily,” [cited by applicant]
Zhang et al., “X-ray structure analysis and crystallographic refinement of lumazine synthase from the hyperthermophile [cited by applicant]
Zhu et al., “QS-21: A Potent Vaccine Adjuvant,” [cited by applicant]
Espinosa et al., “Proteolytic Cleavage of the Plasmodium falciparum Circumsporozoite Protein is a Target of Protective Antibodies,” Journal of Infectious Diseases, Oct. 1, 2015, 212(7):1111-1119, e-published Mar. 11, 20… [cited by applicant]
Altshuler et al. “Production of recombinant antibodies and methods for increasing their affinity” [in Russian], Advances in Biological Chemistry, 2010, vol. 50, p. 203 (title page), 215, 216 and 219-228 and the English … [cited by applicant]