# US 7,745,580 B2 · Compounds useful in the diagnosis and treatment of pregnancy-associated malaria

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,745,580 B2
- Document ID: US7745580B2
- Status: Granted
- Kind: B2
- Application number: 10/543,312
- Filed: 2003-12-30
- Published: 2007-03-08
- Granted: 2010-06-29
- Earliest claimed: 2003-01-27
- Assignees: Kobenhavns Universitet
- Inventors: Thor Grundtvig Theander; Ali Salanti; Lars Hviid; Trine Staalsø; Anja Tatiana Ramstedt Jensen; Thomas Lavstsen; Madelaine Dahlbäck
- Web page: https://patentgrep.com/patent/US7745580B2

## CPC

- C07K 16/205: {Plasmodium}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- Y10S 435/975: Kit
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

The present invention relates to nucleic acid molecules related to the var2csa gene family as well as amino acid sequences encoded by such nucleic acid molecules with respect to their role in mediating adhesion of infected red blood cells to chondroitin sulphate A (CSA) in the placenta which is characteristic for the pathogenesis of pregnancy associated malaria (PAM). Accordingly, The invention provides the use compounds that are related to VAR2CSA polypeptides var2csa nucleic acid molecules as medicaments, as well as it provides pharmaceutical compositions, in particular immunological compositions and vaccines, hereunder nucleotide-based vaccines comprising these compounds. In addition, the invention provides the use of the compounds mentioned for the manufacture of compositions, such as immunogenic compositions. Other aspects of the invention relates to methods of treatment and prevention of pregnancy associated malaria wherein these methods are based on the nucleic acid molecules and polypeptides the invention. As these compounds can also be used as biotechnological tools the invention provides in vitro diagnostic methods and kits comprising reagents and IgGs/antibodies designated to the use in such methods. The invention also relates to methods of identifying agents capable of modulating the VAR2CSA dependent adhesion to CSA and agent capable of interacting with VAR2CSA. Finally, a method for identifying polypeptides, which will induce a specific IgG/antibody response upon administration to a subject is provided by the invention.

## Claims

### Claim 1

An isolated polypeptide comprising an amino acid sequence that is at least 90% identical to a sub-sequence of-SEQ ID NO:2 with a minimum length of 100 amino acids, wherein said amino acid sequence
(i) does not comprise a cysteine-rich inter-domain region (CIDR) domain or Duffy-binding like-γ (DBL-γ) domain, and
(ii) comprises (a) at least one B-cell epitope, (b) at least one T-cell epitope, or (c) at least one B-cell epitope and at least one T-cell epitope, and
(iii) is capable of inducing an immune response against a molecule expressed on the surface of an intact erythrocyte infected by a placental parasite.

### Claim 2 (depends on 1)

An isolated polypeptide according to claim 1, wherein said sub-sequences comprise one or more glycos-amino glucans-binding motifs.

### Claim 3 (depends on 1)

An isolated polypeptide according to claim 1, wherein said amino acid sequence is gender specifically recognised.

### Claim 4 (depends on 1)

An isolated polypeptide according to claim 1, wherein said amino acid sequence is recognised in a parity dependent manner.

### Claim 5 (depends on 1)

An immunogenic composition comprising an isolated polypeptide according to claim 1.

### Claim 6 (depends on 5)

An immunogenic composition according to claim 5, said composition characterised in that it induces an IgG/IgM antibody response.

### Claim 7

An in vitro diagnostic kit comprising:
1) An isolated polypeptide comprising an amino acid sequence that is at least 90% identical to -a sub-sequence of SEQ ID NO:2 with a minimum length of 100 amino acids and wherein said sub-sequence comprises (a) at least one B-cell epitope, (b) at least one T-cell epitope, or (c) at least one B-cell epitope and at least one T-cell epitope;
2) reagents for preparing a suitable medium for carrying out a reaction between an IgG/antibody present in a sample of body fluid or tissue and said sequence, and
3) reagents allowing the detection of the antigen-antibody complexes formed;
wherein said reagents may bear a radioactive or non-radioactive label.