# US 11,672,877 B2 · In vivo immunoimaging of interferon-gamma

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

- Number: US 11,672,877 B2
- Document ID: US11672877B2
- Status: Granted
- Kind: B2
- Application number: 16/640,456
- Filed: 2018-08-23
- Published: 2020-07-02
- Granted: 2023-06-13
- Earliest claimed: 2017-08-23
- Assignees: Wayne State University
- Applicants: Wayne State University
- Inventors: Nerissa Viola; Heather Gibson
- Web page: https://patentgrep.com/patent/US11672877B2

## CPC

- A61K 51/1021: {against cytokines, e.g. growth factors, VEGF, TNF, lymphokines or interferons}
- A61K 49/0058: {Antibodies}
- A61K 51/1093: {conjugates with carriers being antibodies}
- C07K 16/249: {Interferons}
- G01N 33/60: involving radioactive labelled substances
- G16H 20/10: relating to drugs or medications, e.g. for ensuring correct administration to patients
- G16H 20/40: relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
- G16H 30/20: for handling medical images, e.g. DICOM, HL7 or PACS
- Y02A 90/10: Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
- 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)
- 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)
- 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)
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Methods for in vivo immunoimaging including: (a) administering a labeled-antibody conjugate to a subject, wherein the labeled-antibody conjugate includes: an antibody that specifically recognizes and binds to IFN-γ, and a detection label conjugated to the antibody, wherein the detection label is a radionuclide tracer or tluorophore; and (b) detecting the presence of the radiolabeled-antibody conjugate in the subject in vivo by imaging. Embodiments of the present disclosure are directed to labeled-antibody conjugates and therapeutic radionuclide-antibody conjugates.

## Claims

### Claim 1

A method for in vivo immunoimaging interferon gamma (IFN-γ) as a marker of active T cells in a subject with cancer, comprising:
administering a labeled-antibody conjugate to a subject, wherein the labeled-antibody conjugate comprises:
an antibody that specifically binds to IFN-γ, and
a detection label conjugated to the antibody, wherein the detection label is a radionuclide tracer selected from 11C, 13N, 15O, 18F, 44Sc, 45Ti, 52Mn, 64Cu, 68Ga, 76Br, 82Rb, 86Y, 89Zr, 111In, 124I, 43K, 52Fe, 57Co, 67Cu, 67Ga, 77Br, 81Rb, 81mKr, 87mSr, 113mIn, 123I, 127Cs, 129Cs, 132I, 197Hg, 203Pb, 206Bi, or a combination of any two or more thereof; and
detecting the presence of the labeled-antibody conjugate in the subject in vivo by imaging, wherein specific binding of the labeled-antibody conjugate to IFN-γ indicates the presence of activated T cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject received an immunotherapy prior to administering and detecting the presence of the labeled-antibody conjugate, and wherein the mechanism of action of the immunotherapy results in an increased number of tumor-infiltrating lymphocytes in the subject and/or an increased activation state of a tumor-infiltrating lymphocyte population in the subject; or wherein administering and detecting the presence of the labeled-antibody conjugate is performed prior to administration of a therapy to determine the state of active immunity in the subject.

### Claim 3 (depends on 2)

The method of claim 2, wherein the subject received an immunotherapy prior to administering and detecting the presence of the labeled-antibody conjugate, and wherein the mechanism of action of the immunotherapy results in an increased number of tumor-infiltrating lymphocytes in the subject and/or an increased activation state of a tumor-infiltrating lymphocyte population in the subject; and wherein the immunotherapy is an immune checkpoint inhibitor, a cytokine, a vaccine, or an adoptive cell transfer therapy.

### Claim 4 (depends on 1)

The method of claim 1, wherein the subject is human and the antibody specifically binds to human IFN-γ.

### Claim 5 (depends on 1)

The method of claim 1, wherein the antibody is selected from a monoclonal antibody, an antibody fragment, or combination thereof.

### Claim 6 (depends on 5)

The method of claim 5, wherein the antibody is an antibody fragment, and wherein the antibody fragment is a Fab fragment or a diabody.

### Claim 7 (depends on 1)

The method of claim 1, wherein the imaging comprises positron emission tomography (PET) imaging, single photon emission computed tomography (SPECT) imaging, or a both PET and SPECT.

### Claim 8 (depends on 1)

The method of claim 1, wherein the presence of the labeled-antibody conjugate is detected in real time.

### Claim 9 (depends on 1)

The method of claim 1, wherein the radionuclide tracer is conjugated to the antibody with a bifunctional chelator or linker.

### Claim 10 (depends on 9)

The method of claim 9, wherein the radionuclide tracer is conjugated to the antibody with a bifunctional chelator, and wherein the bifunctional chelator comprises a chelator selected from N′-{5-[Acetyl(hydroxy)amino]pentyl}-N-[5-({4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoyl}amino)pentyl]-N-hydroxysuccinamide (DFO), 1,4,7-triazacyclononane-N,N′,N′-triacetic acid (NOTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), ethylenediaminetetraacetic acid (EDTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOPA), diethylenetriaminepentaacetic acid (DTPA), 2,2′-(7-(1-carboxy-4-((2,5-dioxopyrrolidin-1-yl)oxy)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NODA), or a combination of any two or more thereof.

### Claim 11 (depends on 9)

The method of claim 9, wherein the radionuclide tracer is conjugated to the antibody with a bifunctional chelator, and wherein the bifunctional chelator is p-SCN-Bn-DFO or NOTA.