Methods and systems for selection and treatment of patients with inflammatory diseases
Patent Information
- Application Number
- TW108115107
- Authority / Receiving Office
- TW · TW
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2018-12-21
- Filing Date
- 2019-04-30
- Publication Date
- 2026-09-11
- Estimated Expiration
- 2039-04-29
AI Technical Summary
Current treatments for inflammatory, fibrostenotic, and fibrotic diseases like Crohn's disease are inadequate, with many patients experiencing lack of response or loss of response to anti-inflammatory therapies, leading to invasive surgeries with significant risks, and there is a need for individualized therapies based on genetic predisposition.
The use of CD30L inhibitors, identified through genetic polymorphisms such as rs911605 and rs1006026, to target CD30L activity or expression, combined with additional therapeutic agents, for personalized treatment of inflammatory diseases, particularly Crohn's disease, to prevent disease progression and response to standard therapies.
This approach allows for personalized treatment strategies that effectively inhibit CD30L activity, reducing disease severity and preventing invasive surgeries by identifying individuals at risk or non-responsive to standard therapies, thereby improving treatment outcomes.
Abstract
Description
Prior Technology
Content of invention
Implementation
Claims
1. A method for inhibiting or reducing CD30 ligand activity or expression in an individual, the method comprising: a) selecting an individual who has or is suspected of having at least one of an inflammatory disease, a fibrotic stenosis, and a fibrotic degenerative disease; b) identifying the individual as a carrier of a genotype containing polymorphism at at least one of rs911605 and rs1006026; and c) administering an effective amount of an inhibitor of CD30 ligands to the individual to inhibit or reduce CD30 ligand activity or expression in the individual.
2. The method of claim 1, wherein the polymorphism at rs911605 includes the "A" pair gene at 501 of the kernel base of rs911605 (SEQ ID NO: 1), and wherein the polymorphism at rs1006026 includes the "G" pair gene at 501 of the kernel base of rs1006026 (SEQ ID NO: 3).
3. The method of claim 1, wherein the genotype includes the polymorphism at rs911605 and the polymorphism at rs1006026.
4. The method of claim 3, wherein the polymorphism at rs911605 includes the "A" pair gene at 501 of the kernel base of rs911605 (SEQ ID NO: 1), and the polymorphism at rs1006026 includes the "G" pair gene at 501 of the kernel base of rs1006026 (SEQ ID NO: 3).
5. The method of claim 1, wherein identifying the individual as a carrier of the genotype comprises: a) contacting a sample containing genetic material obtained from the individual under standard hybridization conditions with a nucleic acid sequence capable of hybridizing with at least 10 adjacent nucleobases between nucleobases 400 and 600 of at least one of SEQ ID NO: 1 and SEQ ID NO: 3, wherein the at least 10 adjacent nucleobases include the nucleobase at position 501 of at least one of SEQ ID NO: 1 and SEQ ID NO: 3; and b) detecting the binding of the nucleic acid sequence to at least 10 adjacent nucleobases between nucleobases 400 and 600 of at least one of SEQ ID NO: 1 and SEQ ID NO:
2.
6. The method of claim 1, wherein the inhibitor of the CD30 ligand is an antibody or antigen-binding fragment targeting the CD30 ligand or CD30, or a combination thereof.
7. The method of claim 1, further comprising administering to the individual an effective amount of an inhibitor of tumor necrosis factor ligand superfamily member 15 (TL1A).
8. The method of claim 7, wherein the inhibitor of TL1A is an antibody or antigen-binding fragment antagonist targeting TL1A.
9. A method for treating an individual with moderate to severe Crohn's disease, the method comprising: a) identifying the individual with Crohn's disease (CD) as a carrier of a genotype containing at least one of rs911605 and rs1006026 polymorphism; the genotype being associated with the individual's risk of developing a moderate to severe form of CD including obstructive CD; and d) administering to the individual a therapeutically effective amount of an inhibitor of CD30 ligand activity or expression.
10. The method of claim 9 further includes determining whether the individual has or will have at least one of unresponsiveness to standard treatment or loss of response.
11. The method of claim 10, wherein the standard treatment is selected from the group consisting of: glucocorticoid steroids, anti-TNF therapy, anti-α4-β7 therapy (vedolizumab), anti-IL12p40 therapy (ustekinumab), thalidomide, and cytotoxic agents.
12. The method of claim 9, wherein the polymorphism at rs911605 comprises the "A" pair gene at 501 nuclei of rs911605 (SEQ ID NO: 1), and wherein the polymorphism at rs1006026 comprises the "G" pair gene at 501 nuclei of rs1006026 (SEQ ID NO: 3).
13. The method of claim 12, wherein the genotype includes the polymorphism at rs911605 and the polymorphism at rs1006026.
14. The method of claim 9, wherein the inhibitor of CD30 ligand activity is an antibody or antigen-binding fragment or a combination thereof targeting a CD30 ligand or CD30.
15. The method of claim 9, further comprising administering to the individual an effective amount of an inhibitor of tumor necrosis factor ligand superfamily member 15 (TL1A).
16. The method of claim 15, wherein the inhibitor of TL1A is an antibody or antigen-binding fragment antagonist targeting TL1A.
17. A method for characterizing an inflammatory disease in an individual, the method comprising: a) analyzing genetic material in a sample obtained from an individual with an inflammatory disease to detect the presence of a genotype containing at least one of rs911605 and rs1006026; b) characterizing the inflammatory disease as Crohn's disease (CD), wherein the genotype is detected in step (a).
18. The method of claim 17, wherein the genetic material in the sample analyzed in step (a) comprises: a) amplifying at least 15 nucleotides from the genetic material in SEQ ID NO: 5 or SEQ ID NO: 6, the at least 15 nucleotides comprising the nucleotides at the positions indicated by [A / G] in SEQ ID NO: 5 or [A / G] in SEQ ID NO: 6; and b) hybridizing a nucleic acid comprising a nucleic acid sequence including at least one of SEQ ID NO: 5 and SEQ ID NO: 6 with the genetic material.
19. The method of claim 17, wherein the genetic material in the sample analyzed in step (a) comprises: a) amplifying at least 15 nucleobases from the genetic material in SEQ ID NO: 7 or SEQ ID NO: 8, the at least 15 nucleobases comprising the nucleobases at the positions indicated by [A / G] in SEQ ID NO: 7 or [A / G] in SEQ ID NO: 8; and b) hybridizing a nucleic acid comprising a nucleic acid sequence including at least one of SEQ ID NO: 7 and SEQ ID NO: 8 with the genetic material.
20. The method of claim 18 or 19, wherein the nucleic acid contains a detectable molecule.
21. The method of claim 20, further comprising administering to the individual an inhibitor of CD30 ligand activity or expression, wherein the inflammatory disease is characterized as moderate to severe in step (b).
22. The method of claim 21, wherein the inhibitor of CD30 ligand activity is an antibody or antigen-binding fragment or a combination thereof that targets the CD30 ligand or CD30.
23. The method of claim 21, further comprising administering to the individual an effective amount of an inhibitor of tumor necrosis factor ligand superfamily member 15 (TL1A).
24. The method of claim 23, wherein the inhibitor of TL1A is an antibody or antigen-binding fragment antagonist targeting TL1A.
25. The method of claim 17, wherein step (b) characterizing the inflammatory disease as CD further comprises characterizing the inflammatory disease as difficult to treat with standard treatment selected from the group consisting of: glucocorticoid steroids, anti-TNF therapy, anti-α4-β7 therapy (vedozimab), anti-IL12p40 therapy (utectomycin), thalidomide, and cytotoxic agents.
26. The method of claim 25, wherein the CD is further characterized as a blocking CD.
27. Use of a compound comprising an inhibitor of the CD30 ligand for the treatment of carriers of a genotype identified as comprising the "A" pair gene at kernel position 501 of SEQ ID NO: 2, the "G" pair gene at kernel position 501 of SEQ ID NO: 4, or a combination thereof.
28. Use of a combination therapy comprising an inhibitor of the CD30 ligand and an inhibitor of tumor necrosis factor ligand superfamily member 15 (TL1A) for the treatment of carriers of a genotype identified as comprising the "A" pair gene at kernel position 501 of SEQ ID NO: 2, the "G" pair gene at kernel position 501 of SEQ ID NO: 4, or a combination thereof.
29. As claimed in claim 28, wherein the individual is separately administered an inhibitor of the CD30 ligand and an inhibitor of the TL1A.
30. For the purposes of claims 27 or 28, wherein the individual is identified as having or being susceptible to at least one of the following groups of standard treatments that are unresponsive or have lost response: glucocorticoid steroids, anti-TNF therapy, anti-α4-β7 therapy (vedozizumab), anti-IL12p40 therapy (utectomycin), thalidomide, and cytotoxic agents.