Groundbreaking Platform Technology for Specific Binding to Necrotic Cells

• US 20160106851A1
• Filed: 08/06/2015
• Published: 04/21/2016
• Est. Priority Date: 02/06/2013
• Status: Abandoned Application

• Current Assignee: HQ Medical Netherlands BV
• Original Assignee: HQ Medical Netherlands BV
• Inventors: Maring, Markwin Hendrik, Van Beek, Ermond Reijer, Lowik, Clemens Waltherus Gerardus
• Application Number:
  US14/820,386
• Publication Number:
  US 20160106851A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 47/555 pre-targeting systems involving an organic compound, other than a peptide, protein or antibody, for targeting specific cells
• CPC Class Codes: A61K 49/0032 Methine dyes, e.g. cyanine dyes
• CPC Class Codes: A61K 49/0034 Indocyanine green, i.e. ICG, cardiogreen
• CPC Class Codes: A61K 49/0041 Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal in vivo G01N
• CPC Class Codes: A61K 49/0052 Small organic molecules oligomers, polymers, dendrimers A61K49/0054
• CPC Class Codes: A61K 51/0446 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 51/0497 conjugates with a carrier being an organic compounds
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: G01N 2510/00 Detection of programmed cell death, i.e. apoptosis
• CPC Class Codes: G01N 33/574 for cancer

Abstract

A system comprising a targeting molecule for binding necrotic cells; to the system for use as a medicament; to use of the system for diagnosis; to the system for use in treatment of diseases involving necrotic cell death, to a dosage comprising the system; to a method for determining localization of the composition within a sample using said system; and, to a method for treatment of cancers and/or diseases involving necrotic cell death using said system. In particular the invention relates to compositions targeting necrotic cells.

Claims

1. A system comprising a targeting molecule for binding necrotic cells, the targeting molecule being a cyanine that is cell membrane impermeant, is non-activated, is capable of non-covalently binding to intracellular proteins wherein the targeting molecule is neutral or negatively charged, wherein the targeting molecule is selected from:

HQ4, HQ5, HQ6, HQ7, ICG, ZW800, L7, L11, CY3, CY3b, CY3.5, CY5, Dy 676, Dy 681, Dy 731, Dy 751 and Dy 776; and

does not significantly bind to DNA,

wherein the system further comprises one or more of;

(i) an agent selected from an imaging compound, a therapeutic compound, and a release factor;

(ii) a vehicle that is effective for transporting an/the agent; and

(iii) an in the body non-reactive molecule being capable of interacting with a counterpart.

2. A system according to claim 1, wherein the targeting molecule is selected from ZW80, HQ4, HQ5, HQ6, and HQ7.

3. A system according to claim 1, wherein the agent is:

(a) an imaging compound selected from a group consisting a luminescent compound, a radioactive tracer, an MRI contrast or Spectroscopic agent, a PET agent, a RFA (Radio Frequency Ablation) agent, a SPECT agent, an ultrasound microbubble or contrast agent, opto-acoustic nanoparticles or contrast agent, CT contrast agent, a Raman agent, and combinations thereof; and

/or

(b) a therapeutic compound selected from a group consisting of chemo therapeutic agents, photo dynamic compounds, hyper-thermic compounds (including photo thermal agents), immune modulating agents, proteins and peptides, nucleic acids (RNA- or DNA-based), medicaments (like antibodies), and combinations thereof; and

/or

(c) a release factor for stimulating tissue regeneration, such as growth factors and stem cells.

4. A system according to claim 1, wherein the vehicle is selected from a group consisting:

a liposome, a dendrimer, a biodegradable particle, a micelle, a nanoparticle, an acoustic dissociable particle, a pH dissociable particle, a light dissociable particle, a heat dissociable particle, a chelating moiety, and combinations thereof.

5. A system according to claim 1, wherein the in the body non-reactive molecule being capable of interacting with a counterpart is selected from:

a first Click-Chemistry component, a second Click-Chemistry component being complementary to the first Click-Chemistry component, and a component of a self-labelling protein tag such as of Snap-Tag.

6. A system comprising a targeting molecule for binding necrotic cells, the targeting molecule being a cyanine that is cell membrane impermeant, is non-activated, is capable of non-covalently binding to intracellular proteins wherein the targeting molecule is neutral or negatively charged, and does not significantly bind to DNA,

wherein the system further comprises one or more of:

(i) an agent selected from an imaging compound, a therapeutic compound, and a release factor;

(ii) a vehicle that is effective for transporting an/the agent; and

(iii) an in the body non-reactive molecule being capable of interacting with a counterpart for use as a medicament.

7. Use of a system comprising a targeting molecule for binding necrotic cells, the targeting molecule being a cyanine that is cell membrane impermeant, is non-activated, is capable of non-covalently binding to intracellular proteins wherein the targeting molecule is neutral or negatively charged, and does not significantly bind to DNA,

wherein the system further comprises one or more of:

(i) an agent selected from an imaging compound, a therapeutic compound, and a release factor;

(ii) a vehicle that is effective for transporting an/the agent; and

(iii) an in the body non-reactive molecule being capable of interacting with a counterpart, in a diagnostic method selected from MRI, SPECT, PET, RFA (Radio Frequency Ablation), CT, Raman spectroscopy, Ultrasound, Optical and Opto-acoustic.

8. A system comprising a targeting molecule for binding necrotic cells, the targeting molecule being a cyanine that is cell membrane impermeant, is non-activated, is capable of non-covalently binding to intracellular proteins wherein the targeting molecule is neutral or negatively charged, and does not significantly bind to DNA,

wherein the system further comprises one or more of:

(i) an agent selected from an imaging compound, a therapeutic compound, and a release factor;

(ii) a vehicle that is effective for transporting an/the agent; and

(iii) an in the body non-reactive molecule being capable of interacting with a counterpart for use in the treatment of diseases involving necrotic cell death, including infarcts or ischemic injury, such as Myocardial infarct, stroke, and kidney, trauma, such as in a brain, a muscle, a bone, infections or inflammation, such as septic shock, rheumatoid arthritis, and osteonecrosis, degenerative diseases, such as Alzheimer, Parkinson dementia, plaques, such as arteriosclerotic, and amyloid, and Diabetes.

9. Dosage for detection and/or treatment of cancers and/or diseases involving necrotic cell death comprising an effective amount of a system comprising a targeting molecule for binding necrotic cells, the targeting molecule being a cyanine that is cell membrane impermeant, is non-activated, is capable of non-covalently binding to intracellular proteins, wherein the targeting molecule is neutral or negatively charged, and does not significantly bind to DNA,

wherein the system further comprises one or more of:

(i) an agent selected from an imaging compound, a therapeutic compound, and a release factor;

(ii) a vehicle that is effective for transporting an/the agent; and

(iii) an in the body non-reactive molecule being capable of interacting with a counterpart.

10. Dosage according to claim 9, comprising an amount of 0.1-1000 nMole system/kg body weight and/or is provided in a physiological solution of 1-50 ml.

11. A method for determining localization within a sample, said sample comprising a population of cells comprising necrotic cells, comprising:

(a) providing a system comprising a targeting molecule for binding necrotic cells, the targeting molecule being a cya-nine that is cell membrane impermeant, is non-activated, is capable of non-covalently binding to intracellular proteins, wherein the targeting molecule is neutral or negatively charged, and does not significantly bind to DNA,

wherein the system further comprises one or more of;

(i) an agent selected from an imaging compound, a therapeutic compound, and a release factor;

(ii) a vehicle that is effective for transporting an/the agent; and

(iii) an in the body non-reactive molecule being capable of interacting with a counterpart;

(b) performing one or more measurements on the sample with at least a first suitable imaging technique providing a value or values, and;

(c) analysing said value or values of the measurement to determine localization, optionally by comparison with a set of reference values.

12. A method for treatment of cancers and/or dis-eases involving necrotic cell death comprising:

(a) administering a system comprising a targeting molecule for binding necrotic cells, the targeting molecule being a cyanine that is cell membrane impermeant, is non-activated, is capable of non-covalently binding to intracellular proteins, wherein the targeting molecule is neutral or negatively charged, and does not significantly bind to DNA,

wherein the system further comprises one or more of;

(i) an agent selected from an imaging compound, a therapeutic compound, and a release factor;

(ii) a vehicle that is effective for transporting an/the agent; and

(iii) an in the body non-reactive molecule being capable of interacting with a counterpart, wherein the composition com-prises one or more therapeutic compound(s)

(b) determining localization of the composition within the cancer and/or necrotic tissue

(c) activating release of at least the therapeutic com-pound(s) from the vehicle and/or activating the therapeutic compound(s).