# US 12,006,355 B2 · Nanobodies against cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif)

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- Number: US 12,006,355 B2
- Document ID: US12006355B2
- Status: Granted
- Kind: B2
- Application number: 17/544,377
- Filed: 2021-12-07
- Published: 2022-06-02
- Granted: 2024-06-11
- Earliest claimed: 2017-05-30
- Assignees: The Regents of the University of California; Trustees of Dartmouth College
- Applicants: The Regents of the University of California; The Trustees of Dartmouth College
- Inventors: Bruce D. Hammock; Natalia Vasylieva; Jiexian Dong; Christophe Morisseau; Dean R. Madden
- Web page: https://patentgrep.com/patent/US12006355B2

## CPC

- C07K 16/1214: Pseudomonadaceae (F)
- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- C07K 16/40: against enzymes
- G01N 33/56911: {Bacteria}
- C07K 2317/22: from camelids, e.g. camel, llama or dromedary
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- G01N 2333/21: from Pseudomonadaceae (F)
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Provided are VHH or nanobodies that specifically bind to cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif), and uses thereof for diagnosis and treatment of Pseudomonas infection.

## Claims

### Claim 1

A method of reducing, inhibiting, mitigating and/or reversing one or more symptoms caused by a Pseudomonas aeruginosa infection in a subject in need thereof, the method comprising administering to the subject an effective amount of an isolated, recombinant, synthetic and/or non-natural VHH molecule that specifically binds to cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif) molecules secreted by Pseudomonas aeruginosa, wherein the anti-Cif VHH molecule comprises:
a) a CDR1 comprising SEQ ID NO:2, a CDR2 comprising SEQ ID NO:3 and a CDR3 comprising SEQ ID NO:4;
b) a CDR1 comprising SEQ ID NO:6, a CDR2 comprising SEQ ID NO:7 and a CDR3 comprising SEQ ID NO:8;
c) a CDR1 comprising SEQ ID NO:10, a CDR2 comprising SEQ ID NO:11 and a CDR3 comprising SEQ ID NO:12;
d) a CDR1 comprising SEQ ID NO:14, a CDR2 comprising SEQ ID NO:15 and a CDR3 comprising SEQ ID NO:16;
e) a CDR1 comprising SEQ ID NO:18, a CDR2 comprising SEQ ID NO:19 and a CDR3 comprising SEQ ID NO:20;
f) a CDR1 comprising SEQ ID NO:22, a CDR2 comprising SEQ ID NO:23 and a CDR3 comprising SEQ ID NO:24;
g) a CDR1 comprising SEQ ID NO:26, a CDR2 comprising SEQ ID NO:27 and a CDR3 comprising SEQ ID NO:28;
h) a CDR1 comprising SEQ ID NO:30, a CDR2 comprising SEQ ID NO:31 and a CDR3 comprising SEQ ID NO:32;
i) a CDR1 comprising SEQ ID NO:34, a CDR2 comprising SEQ ID NO:35 and a CDR3 comprising SEQ ID NO:36;
j) a CDR1 comprising SEQ ID NO:38, a CDR2 comprising SEQ ID NO:39 and a CDR3 comprising SEQ ID NO:40;
k) a CDR1 comprising SEQ ID NO:42, a CDR2 comprising SEQ ID NO:43 and a CDR3 comprising SEQ ID NO:44;
l) a CDR1 comprising SEQ ID NO:46, a CDR2 comprising SEQ ID NO:47 and a CDR3 comprising SEQ ID NO:48;
m) a CDR1 comprising SEQ ID NO:50, a CDR2 comprising SEQ ID NO:51 and a CDR3 comprising SEQ ID NO:52;
o) a CDR1 comprising SEQ ID NO:58, a CDR2 comprising SEQ ID NO:59 and a CDR3 comprising SEQ ID NO:60;
p) a CDR1 comprising SEQ ID NO:62, a CDR2 comprising SEQ ID NO:63 and a CDR3 comprising SEQ ID NO:64;
q) a CDR1 comprising SEQ ID NO:66, a CDR2 comprising SEQ ID NO:67 and a CDR3 comprising SEQ ID NO:68; or
r) a CDR1 comprising SEQ ID NO:70, a CDR2 comprising SEQ ID NO:71 and a CDR3 comprising SEQ ID NO:72.

### Claim 2 (depends on 1)

The method of claim 1, wherein the VHH molecule is administered via a route selected from the group consisting of intrapulmonary, inhalational, intravenous, intramuscular, subcutaneous, intradermal, transcutaneous, topical, intrathecal, intralesional, transmucosal, intra-arterial, intraperitoneal, intraventricular and intracranial.