Methods and compositions for enhancing immune response

Patent metadata

Field	Value
Publication number	US-9801947-B2
Application number	US-201414507139-A
Country	US
Kind code	B2
Filing date	Oct 6, 2014
Priority date	Apr 10, 2003
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

Methods and compositions for enhancing the immune response to an IRM compound by depositing within a localized tissue region an IRM depot preparation that provides an extended residence time of active IRM within the localized tissue region.

First claim

What is claimed is:

1. A method of enhancing a subject's immune response, the method comprising:
depositing within a localized tissue region of the subject an immune response modifier (IRM) depot preparation that provides an extended residence time within the localized tissue region, wherein the IRM comprises an IRM portion of the formula

and having IRM activity; and
a portion having antigenic activity that comprises:
an antigenic portion, or
a solid support to which the antigenic moiety is paired;

wherein the immune response modifier portion is covalently coupled to the portion having antigenic activity through R 1 ;
wherein the immune response modifier portion comprises an imidazoquinoloine amine; a tetrahydroimidazolequinoline amine; an imidazopyridine amine; an imidazonapthyridine amine; or a tetrahydroimidazonaphihydine amine;
wherein the antigenic portion or antigenic moiety comprises a polypeptide, a polynucleotide, or a lipopolysaccharide;
wherein:
R 1 is a linker group;
R 2 is selected from the group consisting of:
-hydrogen;
-alkyl;
-alkenyl;
-aryl;
-substituted aryl;
-heteroaryl;
-substituted heteroaryl;
-alkyl-O-alkyl;
-alkyl-S-alkyl;
-alkyl-O-aryl;
-alkyl-S-aryl:
-alkyl-O-alkenyl;
-alkyl-S-alkenyl; and
-alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
—OH;
-halogen;
—N(R 5 ) 2 ;
—CO—N(R 5 ) 2 ;
—CS—N(R 5 ) 2 ;
—SO 2 —N(R 5 ) 2 ;
—NR 5 —CO—C 1-10 alkyl;
—NR 5 —CS—C 1-10 alkyl;
—NR 5 —SO 2 —C 1-10 alkyl;
—CO—C 1-10 alkyl;
—CO—O—C 1-10 alkyl;
—N 3 ;
-aryl;
-substituted aryl;
-heteroaryl;
-substituted heteroaryl;
-heterocyclyl;
-substituted heterocyclyl;
—CO-aryl;
—CO-(substituted aryl);
—CO-heteroaryl; and
—CO-(substituted heteroaryl);

R 3 and R 4 are each independently:
-hydrogen;
-halogen;
-alkyl;
-alkenyl;
—O-alkyl;
—S-alkyl; and
—N(R 5 ) 2 ;

or when taken together, R 3 and R 4 form a fused aryl or heteroaryl group that is optionally substituted by one or more substituents selected from the group consisting of;
-halogen;
-alkyl;
-alkenyl;
—O-alkyl;
—S-alkyl; and
—(R 5 ) 2 ;

or when taken together, R 3 and R 4 form a fused 5 to 7 membered saturated ring, optionally containing one or more heteroatoms and optionally substituted by one or more substituents selected from the group consisting of:
-halogen;
-alkyl;
-alkenyl,
—O-alkyl,
—S-alkyl, and
—N(R 5 ) 2 , and

each R 5 is independently hydrogen or C 1-10 alkyl.

2. The method of claim 1 , wherein the localized tissue region comprises a breast cancer tumor, a stomach cancer tumor, a lung cancer tumor, a head or neck cancer tumor, a colorectal cancer tumor, a renal cell carcinoma tumor, a pancreatic cancer tumor, a basal cell carcinoma tumor, a cervical cancer tumor, a melanoma cancer tumor, a prostate cancer tumor, ovarian cancer tumor, or a bladder cancer tumor.

3. The method of claim 1 , further comprising depositing a vaccine antigen within the localized tissue region.

4. The method of claim 3 , wherein the vaccine antigen is not physically or chemically linked to the IRM.

5. The method of claim 3 , wherein the subject's immune response to an antigen is enhanced, and wherein the antigen is an endogenous antigen.

6. The method of claim 1 , wherein the IRM depot preparation comprises an IRM compound attached to support material.

7. The method of claim 1 , wherein the IRM depot preparation comprises solid particles of IRM compound.

8. The method of claim 1 , wherein the IRM depot preparation comprises an emulsion.

9. The method of claim 1 , wherein the IRM depot preparation comprises micelles.

10. The method of claim 1 , wherein the IRM depot preparation comprises IRM within a biodegradable polymer matrix.

11. The method of claim 1 , wherein the IRM depot preparation comprises IRM compound incorporated into lipid membranes, lipid vesicles, or liposomes.

12. The method of claim 1 , wherein the IRM depot preparation provides pulsed delivery of an IRM compound.

13. The method of claim 1 , wherein the IRM depot preparation comprises an osmotically driven cylinder.

14. The method of claim 1 , wherein the IRM depot preparation is delivered within the localized tissue region using needle injection.

15. The method of claim 1 , wherein the IRM depot preparation is delivered within the localized tissue region using surgical implantation.

16. The method of claim 1 , wherein the IRM depot preparation is delivered within the localized tissue region using laparoscopic implantation.

17. The method of claim 1 , wherein the IRM depot preparation is delivered within the localized tissue region using catheter implantation.

18. The method of claim 1 , wherein the IRM depot preparation is delivered within the localized tissue region using a microneedle array.

19. The method of claim 1 , wherein the IRM depot preparation is delivered within the localized tissue region using high-velocity particle implantation.

20. The method of claim 1 , wherein the IRM depot preparation is delivered within the localized tissue region using an image guiding technique selected from ultrasound, MRI, or real-time X-ray fluoroscopy.

Assignees

• 3M Innovative Properties Co

Inventors

• Miller Richard L
• Tomai Mark A
• Kedl Ross M
• Zarraga Isidro Angelo Eleazar
• Ortiz Ronnie
• Stoesz James D
• Wightman Paul D

Classifications

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K31/44

  Non condensed pyridines; Hydrogenated derivatives thereof · CPC title

• A61K47/48046 Primary

  Human Necessities · mapped topic

• A61K2039/55555

  Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers · CPC title