CRP capture/detection of gram positive bacteria

Patent metadata

Field	Value
Publication number	US-11034744-B2
Application number	US-201916669805-A
Country	US
Kind code	B2
Filing date	Oct 31, 2019
Priority date	Dec 18, 2013
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

Abstract

Described herein are engineered microbe-targeting molecules, microbe-targeting articles, kits comprising the same, and uses thereof. Such microbe-targeting molecules, microbe-targeting articles, or the kits comprising the same can bind or capture of a microbe or microbial matter thereof, and can thus be used in various applications, such as diagnosis or treatment of an infection caused by microbes in a subject or any environmental surface.

First claim

What is claimed is:

1. A microbe-targeting molecule comprising:
a. at least one first domain comprising at least a portion of a c-reactive protein (CRP);
b. at least one second domain comprising at least a portion of a domain selected from the group consisting of:
(i) Fc region of an immunoglobulin;
(ii) microbe-binding domain of a microbe-binding protein, wherein the microbe-binding protein is not CRP;
(ii) neck region of a lectin;
(iv) a detectable label;
(v) domain for conjugation to surface of a carrier scaffold;
(vi) pattern recognition receptor domain of CRP; and
(vii) any combinations of (i)-(vi); and
a linker conjugating the first and second domains, and
wherein the molecule is a multimeric molecule.

2. The microbe-targeting molecule of claim 1 , wherein the multimeric molecule is formed by: interactions between the linkers of different molecules forming the multimeric molecule; or the linker and the second domain of different molecules forming the multimeric molecule; or the second domains of different molecules forming the multimeric molecule.

3. The microbe-targeting molecule of claim 1 , wherein the Fc region comprises at least one mutation.

4. The microbe-targeting molecule of claim 1 , wherein the microbe-binding protein is a carbohydrate binding protein.

5. The microbe-targeting molecule of claim 4 , wherein the microbe-binding domain is a carbohydrate recognition domain (CRD) of the carbohydrate binding protein.

6. The microbe-targeting molecule of claim 5 , wherein the CRD is from a lectin or ficolin.

7. The microbe-targeting molecule of claim 1 , wherein the second domain comprises at least a portion of Fc region of an immunoglobulin and at least a portion of the neck region of a lectin.

8. The microbe-targeting molecule of claim 1 , wherein the detectable molecule is selected from the group consisting of biotin, fluorophore, luminescent or bioluminescent marker, a radiolabel, an enzyme, an enzyme substrate, a quantum dot, an imaging agent, a gold particle, and any combinations thereof.

9. The microbe-targeting molecule of claim 1 , wherein the domain for conjugation to surface of a carrier scaffold comprises an amino group, a N-substituted amino group, a carboxyl group, a carbonyl group, an acid anhydride group, an aldehyde group, a hydroxyl group, an epoxy group, a thiol, a disulfide group, an alkenyl group, a hydrazine group, a hydrazide group, a semicarbazide group, a thiosemicarbazide group, one partner of a binding pair, an amide group, an aryl group, an ester group, an ether group, a glycidyl group, a halo group, a hydride group, an isocyanate group, an urea group, or an urethane group.

10. The microbe-targeting molecule of claim 1 , wherein the microbe-targeting molecule is conjugated to a surface of a carrier scaffold.

11. The microbe-targeting molecule of claim 10 , wherein the carrier scaffold is selected from the group consisting of a nucleic acid scaffold, a protein scaffold, a lipid scaffold, a polymeric scaffold, a dendrimer, a particle, a bead, a nanotube, a microtiter plate, a medical apparatus or implant, a microchip, a filtration device, a membrane, a diagnostic strip, a dipstick, an extracorporeal device, a spiral mixer, a hollow-fiber tube, a living cell, magnetic material, hollow fiber, and any combinations thereof.

12. A pharmaceutical composition comprising a microbe-targeting molecule of claim 1 and a pharmaceutically acceptable carrier.

13. The microbe-targeting molecule of claim 10 , wherein the carrier scaffold is a biological tissue or organ.

Assignees

• Harvard College

Inventors

• Watters Alexander L
• Ingber Donald E
• Cartwright Mark J
• Super Michael
• Rottman Martin
• Murray Evangelia
• Dusel Brendon

Classifications

• G01N33/569 Primary

  for microorganisms, e.g. protozoa, bacteria, viruses · CPC title

• C07K2319/33

  fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies · CPC title

• G01N33/6854

  Immunoglobulins · CPC title

• A61K38/00

  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) · CPC title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title