# US 2019/0375796 A1 · Engineered Cyclic Peptides

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- Number: US 2019/0375796 A1
- Document ID: US20190375796A1
- Status: Published application
- Kind: A1
- Application number: 16/435,350
- Filed: 2019-06-07
- Published: 2019-12-12
- Earliest claimed: 2018-06-08
- Assignees: Glympse Bio, Inc.
- Applicants: Glympse Bio, Inc.
- Inventors: Faycal Touti; Gabriel Kwong
- Web page: https://patentgrep.com/patent/US20190375796A1

## CPC

- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- C07K 1/12: by hydrolysis {, i.e. solvolysis in general}
- C07K 11/02: cyclic, e.g. valinomycins {; Derivatives thereof}
- C12Q 1/37: involving peptidase or proteinase
- G01N 33/54306: {Solid-phase reaction mechanisms}
- G01N 33/54313: {the carrier being characterised by its particulate form}
- G01N 33/54393: {Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding}
- G01N 33/68: involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)}
- 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)
- G01N 2333/96494: Matrix metalloproteases, e. g. 3.4.24.7
- G01N 2800/085: Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

An engineered cyclic peptide provides structural constraints to resist non-specific degradation in the human body and includes environment-specific cleavage sites to allow release of a linearized peptide upon reaching a target environment. The linearized peptide can include a reporter molecule or a bioactive therapeutic such that the cyclic peptide is essentially inactive at administration and in circulation but becomes reactive only upon exposure to target-specific environmental factors such as a specific combination of differentially-expressed proteases associated with a target tissue or disease state. The peptides can include tuning that modulate distribution by targeting the particle to specific tissue, bodily fluids, or cell types.

## Claims

### Claim 1

An engineered cyclic peptide comprising:
one or more cleavage sites cleavable within a target environment and generally resistant to cleavage outside a target environment, wherein cleavage of the one or more cleavage sites releases a linearized peptide reactive with the target environment.

### Claim 2 (depends on 1)

The engineered cyclic peptide of claim 1 wherein the target environment is a tumor.

### Claim 3 (depends on 1)

The engineered cyclic peptide of claim 1 wherein the target environment is a biological fluid.

### Claim 4 (depends on 3)

The engineered cyclic peptide of claim 3 wherein the biological fluid is blood.

### Claim 5 (depends on 1)

The engineered cyclic peptide of claim 1 wherein the cleavage site is cleaved by an enzyme present in the target environment.

### Claim 6 (depends on 5)

The engineered cyclic peptide of claim 5 wherein the enzyme is known to be expressed with a certain disease or medical condition.

### Claim 7 (depends on 6)

The engineered cyclic peptide of claim 6 wherein the linearized peptide is a therapeutic peptide operable to treat the disease or medical condition.

### Claim 8 (depends on 1)

The engineered cyclic peptide of claim 1 wherein the linearized peptide is bioactive within the target environment.

### Claim 9 (depends on 1)

The engineered cyclic peptide of claim 1 wherein the linearized peptide is cleavable in response to pH of the target environment.

### Claim 10 (depends on 1)

The engineered cyclic peptide of claim 1 wherein the cyclic peptide is a cyclic depsipeptide and the one or more cleavage sites comprise an ester bond.

### Claim 11 (depends on 1)

The engineered cyclic peptide of claim 1 wherein the cyclic peptide is a macrocyclic peptide.

### Claim 12 (depends on 1)

The engineered cyclic peptide of claim 1 further comprising a carrier.

### Claim 13 (depends on 12)

The engineered cyclic peptide of claim 12 wherein the carrier comprises a poly ethylene glycol (PEG) scaffold of covalently linked PEG subunits.

### Claim 14 (depends on 1)

The engineered cyclic peptide of claim 1 wherein the linearized peptide is a detectable reporter

### Claim 15 (depends on 14)

The engineered cyclic peptide of claim 14 wherein the detectable reporter comprises one selected from the group consisting of: a volatile organic compound; an elemental mass tag; a peptide comprising one or more D-amino acids; a nucleic acid; and a neoantigen.

### Claim 16 (depends on 14)

The engineered cyclic peptide of claim 14 wherein the detectable reporter comprises an elemental mass tag comprising an element of atomic number greater than 20.

### Claim 17 (depends on 14)

The engineered cyclic peptide of claim 14 wherein the reporter comprises an antigen detectable by a hybridization assay.

### Claim 18 (depends on 1)

The engineered cyclic peptide of claim 1 wherein the one or more cleavage sites comprise a plurality of different cleavage sites.

### Claim 19 (depends on 18)

The engineered cyclic peptide of claim 18 wherein the plurality of different cleavage sites are cleaved by different enzymes.

### Claim 20 (depends on 18)

The engineered cyclic peptide of claim 18 wherein cleavage of two or more of the plurality of different cleavage sites is required to release the linearized peptide.

### Claim 21 (depends on 20)

The engineered cyclic peptide of claim 20 wherein the two or more of the plurality of different cleavage sites must be cleaved in a specific order to release the linearized peptide.

### Claim 22 (depends on 21)

The engineered cyclic peptide of claim 21 further comprising a tuning domain that modifies a distribution or residence time of the engineered cyclic peptide within a subject when administered to the subject.

### Claim 23 (depends on 22)

The engineered cyclic peptide of claim 22 further comprising a plurality of tuning domains wherein the tuning domains comprise ligands for receptors of a specific cell or a specific tissue type.

### Claim 24 (depends on 23)

The engineered cyclic peptide of claim 23 wherein the ligands promote accumulation of the engineered cyclic peptide in the specific tissue type or body compartment, wherein the ligands each comprise one selected from the group consisting of a small molecule; a peptide; an antibody; a fragment of an antibody; a nucleic acid; and an aptamer.

### Claim 25 (depends on 22)

The engineered cyclic peptide of claim 22 further comprising a plurality of tuning domains wherein the tuning domains comprise hydrophobic chains that facilitate diffusion of the engineered cyclic peptide across a cell membrane.