# US 2008/0187488 A1 · Phage antibodies to radiation-inducible neoantigens

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- Number: US 2008/0187488 A1
- Document ID: US20080187488A1
- Status: Published application
- Kind: A1
- Application number: 11/953,780
- Filed: 2007-12-10
- Published: 2008-08-07
- Earliest claimed: 2001-11-09
- Assignees: Vanderbilt University
- Inventors: Dennis E. Hallahan; Raymond Mernaugh
- Web page: https://patentgrep.com/patent/US20080187488A1

## CPC

- A61K 51/1203: {in a form not provided for by groups A61K51/1206 - A61K51/1296, e.g. cells, cell fragments, viruses, virus capsides, ghosts, red blood cells, viral vectors}
- A61B 5/0071: {by measuring fluorescence emission}
- A61B 6/481: {involving the use of contrast agents}
- A61B 6/508: {for non-human patients}
- A61B 8/481: {involving the use of contrast agents, e.g. microbubbles introduced into the bloodstream}
- A61K 41/00: Medicinal preparations obtained by treating materials with wave energy or particle radiation {; Therapies using these preparations}
- A61K 41/0038: {Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10)}
- A61K 51/1255: {Granulates, agglomerates, microspheres}
- A61N 5/10: X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2848: {against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61}
- C07K 16/2854: {against selectins, e.g. CD62}
- C07K 16/30: from tumour cells
- C12Q 1/6809: Methods for determination or identification of nucleic acids involving differential detection
- G01N 33/6854: {Immunoglobulins}
- G01R 33/281: {Means for the use of in vitro contrast agents (G01R33/282 takes precedence; involving use of a contrast agent in MR imaging G01R33/5601; in vivo contrast agents A61K49/0002)}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/622: Single chain antibody (scFv)
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- 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)
- A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- 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)
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)

## Abstract

A method for identifying a molecule that binds an irradiated tumor in a subject and molecules identified thereby. The method includes the steps of: (a) exposing a tumor to ionizing radiation; (b) administering to a subject a library of diverse molecules; and (c) isolating from the tumor one or more molecules of the library of diverse molecules, whereby a molecule that binds an irradiated tumor is identified. Also provided are therapeutic and diagnostic methods using targeting ligands that bind an irradiated tumor.

## Claims

### Claim at position 1

1-22. (canceled)

### Claim 23

An immunoconjugate composition comprising a single chain fragment variable (scFv) antibody or an Fab antibody that binds to a radiation-inducible neoantigen.

### Claim 24 (depends on 23)

The immunoconjugate composition of claim 23, wherein the immunoconjugate is polyvalent.

### Claim 25 (depends on 23)

The immunoconjugate composition of claim 23, further comprising a therapeutic agent.

### Claim 26 (depends on 25)

The immunoconjugate composition of claim 25, wherein the therapeutic agent is selected from the group consisting of a virus, a radionuclide, a cytotoxin, a therapeutic gene, and a chemotherapeutic agent.

### Claim 27 (depends on 23)

The immunoconjugate composition of claim 23, wherein the single chain fragment variable (scFv) antibody or Fab antibody is humanized.

### Claim 28 (depends on 23)

The immunoconjugate composition of claim 23, wherein the single chain fragment variable (scFv) antibody is encoded by a nucleic acid encoding an scFv antibody having an amino acid sequence selected from the group consisting of SEQ ID NOs: 18, 20, 22, and 24, or by a nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 17,19, 21, and 23.

### Claim 29 (depends on 23)

The immunoconjugate composition of claim 23, wherein the single chain fragment variable (scFv) antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 18, 20, 22, and 24.

### Claim 30 (depends on 23)

The immunoconjugate composition of claim 23, in a pharmaceutically acceptable carrier.

### Claim 31 (depends on 23)

The immunoconjugate composition of claim 23, further comprising a detectable label.

### Claim 32 (depends on 31)

The immunoconjugate composition of claim 31, wherein the detectable label is detectable in vivo.

### Claim 33 (depends on 32)

The immunoconjugate composition of claim 32, wherein the detectable label comprises a label that can be detected using magnetic resonance imaging, scintigraphic imaging, ultrasound, or fluorescence.

### Claim 34 (depends on 33)

The immunoconjugate composition of claim 33, wherein the label that can be detected using scintigraphic imaging comprises a radionuclide label.

### Claim 35 (depends on 34)

The immunoconjugate composition of claim 34, wherein the radionuclide label comprises 131I or 99mTc.

### Claim 36

A polyvalent immunoconjugate composition, the polyvalent immunoconjugate composition comprising a plurality of antibodies or antibody fragments selected from the group consisting of single chain fragment variable (scFv) antibodies, Fab antibodies, and combinations thereof, wherein the plurality of antibodies or antibody fragments bind to a plurality of different epitopes, and wherein at least one of the epitopes is present on a radiation-inducible neoantigen.

### Claim 37 (depends on 36)

The polyvalent immunoconjugate composition of claim 36, wherein at least one of the plurality of different epitopes is present on a vascular endothelial cell.

### Claim at position 17

38-53. (canceled)

### Claim 54 (depends on 23)

A method of targeting a therapeutic agent to a target tissue, the method comprising:
(a) providing the immunoconjugate composition of claim 23 conjugated to a therapeutic agent, wherein the immunoconjugate composition of claim 23 is capable of binding to a radiation-inducible neoantigen;
(b) irradiating the target tissue to induce expression of the radiation-inducible neoantigen in the target tissue; and
(c) contacting the irradiated target tissue with the immunoconjugate composition of claim 23 under conditions sufficient for binding of the antibody or antibody fragment to the radiation-inducible neoantigen, whereby the therapeutic agent is targeted to the target tissue.

### Claim 55 (depends on 23)

A method for suppressing the growth of a tumor in a subject, the method comprising:
(a) exposing the tumor to radiation, whereby a radiation-inducible neoantigen is expressed; and
(b) administering to the subject bearing the tumor an effective amount of the immunoconjugate composition of claim 23 conjugated to a therapeutic agent, wherein the immunoconjugate composition of claim 23 binds to the radiation-inducible neoantigen, whereby growth of the tumor is suppressed.

### Claim 56 (depends on 23)

A method of detecting a tumor in a subject, the method comprising:
(a) exposing a suspected tumor to ionizing radiation;
(b) administering to the subject the immunoconjugate composition of claim 23 conjugated to a detectable label, wherein the immunoconjugate composition of claim 23 binds to a radiation-inducible neoantigen; and
(c) detecting the detectable label, whereby a tumor is detected.

### Claim 57 (depends on 23)

A method for detecting a tumor in a subject, the method comprising:
(a) exposing a suspected tumor to ionizing radiation;
(b) removing a portion of the suspected tumor;
(c) contacting the suspected tumor in vitro with the immunoconjugate composition of claim 23, wherein the immunoconjugate composition of claim 23 comprises:
(i) an antibody or antibody fragment that binds to a radiation-inducible neoantigen; and
(ii) a detectable label; and
(d) detecting the detectable label, whereby a tumor is diagnosed.
