Haptens of olanzapine

Patent metadata

Field	Value
Publication number	US-9303041-B2
Application number	US-201313970653-A
Country	US
Kind code	B2
Filing date	Aug 20, 2013
Priority date	Aug 21, 2012
Publication date	Apr 5, 2016
Grant date	Apr 5, 2016

Abstract

The invention relates to compounds of Formula I, wherein R 1 , R 2 , and R 3 are defined in the specification, useful for the synthesis of novel conjugates and immunogens derived from olanzapine. The invention also relates to conjugates of an olanzapine hapten and a protein.

First claim

We claim:

1. The compound of Formula I:

wherein:
R 1 is H,

 CH 2 NH 2 , or CH 2 NHC(O)(CH 2 ) m CO 2 H;
R 2 is H,

 CH 2 NH 2 , or CH 2 NHC(O)(CH 2 ) m CO 2 H;
R 3 is H; provided that either R 1 or R 2 must be H, and further provided that R 1 and R 2 may not all be H simultaneously;
m is 1, 2, 3, 4, or 5; and
n is 1, 2, 3, 4, or 5.

2. The compound of claim 1 :
wherein:
R 1 is

 CH 2 NH 2 , or CH 2 NHC(O)(CH 2 ) m CO 2 H;
R 2 is H;
R 3 is H;
m is 1, 2, 3, 4, or 5; and
n is 1, 2, 3, 4, or 5.

3. The compound of claim 1
wherein:
R 1 is H,
R 2 is

 CH 2 NH 2 , or CH 2 NHC(O)(CH 2 ) m CO 2 H;
R 3 is H;
m is 1, 2, 3, 4, or 5; and
n is 1, 2, 3, 4, or 5.

4. The compound of claim 1
wherein:
R 1 is H,

 CH 2 NH 2 , or CH 2 NHC(O)(CH 2 ) m CO 2 H;
R 2 is H,

 CH 2 NH 2 , or CH 2 NHC(O)(CH 2 ) m CO 2 H; provided that either R 1 or R 2 must be H, and further provided that both R 1 and R 2 may not be H simultaneously;
R 3 is H;
m is 1, 2, 3, 4, or 5; and
n is 1, 2, 3, 4, or 5.

5. The compound of claim 1
wherein:
R 1 is H,

 CH 2 NH 2 , or CH 2 NHC(O)(CH 2 ) m CO 2 H;
R 2 is H,

 CH 2 NH 2 , or CH 2 NHC(O)(CH 2 ) m CO 2 H; provided that either R 1 or R 2 must be H, and further provided that both R 1 and R 2 may not be H simultaneously;
R 3 is H;
m is 1, 2, 3, 4, or 5; and n is 1, 2, 3, 4, or 5.

6. The compounds of claim 1 , selected from the group consisting of:

7. The compound of claim 6 which is:

8. The compound of claim 6 which is:

9. A conjugate of the compound of claim 1 and an immunogenic carrier, wherein the immunogenic carrier is keyhole limpet hemocyanin, bovine thyroglobulin, or ovalbumin.

10. A conjugate of the compound of claim 2 and an immunogenic carrier, wherein the immunogenic carrier is keyhole limpet hemocyanin, bovine thyroglobulin, or ovalbumin.

11. A conjugate of the compound of claim 3 and an immunogenic carrier, wherein the immunogenic carrier is keyhole limpet hemocyanin, bovine thyroglobulin, or ovalbumin.

12. A conjugate of the compound of claim 4 and an immunogenic carrier, wherein the immunogenic carrier is keyhole limpet hemocyanin, bovine thyroglobulin, or ovalbumin.

13. A conjugate of the compound of claim 5 and an immunogenic carrier, wherein the immunogenic carrier is keyhole limpet hemocyanin, bovine thyroglobulin, or ovalbumin.

14. The conjugate of claim 9 wherein the compound is:

15. The conjugate of claim 9 wherein the compound is:

16. The conjugate of claim 9 wherein the compound is:

17. The conjugate of claim 9 wherein the compound is:

18. A product made by the process of contacting a compound of claim 1 with an immunogenic carrier, wherein the immunogenic carrier is keyhole limpet hemocyanin, bovine thyroglobulin, or ovalbumin.

19. A product made by the process of contacting a compound of claim 2 with an immunogenic carrier, wherein the immunogenic carrier is keyhole limpet hemocyanin, bovine thyroglobulin, or ovalbumin.

20. A product made by the process of contacting a compound of claim 3 with an immunogenic carrier, wherein the immunogenic carrier is keyhole limpet hemocyanin, bovine thyroglobulin, or ovalbumin.

21. A product made by the process of contacting a compound of claim 4 with an immunogenic carrier, wherein the immunogenic carrier is keyhole limpet hemocyanin, bovine thyroglobulin, or ovalbumin.

22. A product made by the process of contacting a compound of claim 5 with an immunogenic carrier, wherein the immunogenic carrier is keyhole limpet hemocyanin, bovine thyroglobulin, or ovalbumin.

23. The product of claim 18 wherein the compound is:

24. The product of claim 18 wherein the compound is:

25. The product of claim 18 wherein the compound is:

26. The product of claim 18 wherein the compound is:

27. The compound of claim 1
wherein:
R 1 is H,

 CH 2 NH 2 , or CH 2 NHC(O)(CH 2 ) m CO 2 H;
R 2 is H,

 CH 2 NH 2 , or CH 2 NHC(O)(CH 2 ) m CO 2 H; provided that either R 1 or R 2 must be H, and further provided that both R 1 and R 2 may not be H simultaneously;
R 3 is H;
m is 1, 2, 3, 4, or 5; and
n is 1, 2, 3, 4, or 5.

28. A conjugate of the compound of claim 27 and an immunogenic carrier, wherein the immunogenic carrier is selected from keyhole limpet hemocyanin, ovalbumin or bovine thyroglobulin.

29. A product made by the process of contacting a compound of claim 27 with an immunogenic carrier, wherein the immunogenic carrier is selected from keyhole limpet hemocyanin, ovalbumin or bovine thyroglobulin.

Assignees

• Janssen Pharmaceutica Nv
• Ortho Clinical Diagnostics Inc

Inventors

• Donahue Matthew Garrett
• Gong Yong
• Salter Rhys
• Hryhorenko Eric
• Decory Thomas R
• Remmerie Bart
• Sankaran Banumathi

Classifications

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• C07D495/04 Primary

  Ortho-condensed systems · CPC title

• C07K14/47

  from mammals · CPC title

• A61K47/646

  the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines · CPC title

• A61K47/643

  Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL] · CPC title