Claims for Patent: 11,191,766

Summary for Patent: 11,191,766

Title:	Methods of treating pediatric cancers
Abstract:	A method of treating a pediatric cancer in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, or a pharmaceutically acceptable salt thereof, or a combination thereof.
Inventor(s):	Cox Michael, Nanda Nisha
Assignee:	Loxo Oncology, Inc.
Application Number:	US16739845
Patent Claims:	2. The method of claim 1 , wherein sodium citrate includes at least one of sodium citrate monohydrate and sodium citrate dihydrate.3. The method of claim 1 , wherein sodium citrate includes sodium citrate dihydrate.4. The method of claim 1 , wherein the subject is an infant claim 1 , child claim 1 , or adolescent.5. The method of claim 1 , wherein the pediatric cancer is selected from the group consisting of: congenital mesoblastic nephroma claim 1 , Ph-like acute lymphoblastic leukemia claim 1 , infantile fibrosarcoma claim 1 , pediatric high-grade glioma (HGG) claim 1 , diffuse intrinsic pontine gliomas (DIPGs) claim 1 , pediatric papillary thyroid carcinoma claim 1 , soft tissue sarcoma claim 1 , and spindle cell sarcoma.6. The method of claim 1 , wherein the pediatric cancer is associated with or having a dysregulation of a NTRK gene claim 1 , a Trk protein claim 1 , or expression claim 1 , or activity claim 1 , or level of the same.7. The method of claim 6 , wherein the dysregulation of a NTRK gene claim 6 , a Trk protein claim 6 , or expression claim 6 , or activity claim 6 , or level of the same is a chromosome translocation that results in the translation of a Trk fusion protein.8. The method of claim 7 , wherein the Trk fusion protein is selected from the group consisting of ETV6-NTRK3 claim 7 , RET/NTRK1 claim 7 , TPM3-NTRK1 claim 7 , BTBD1-NTRK3 claim 7 , VCL-NTRK2 claim 7 , AGBL4-NTRK2 claim 7 , LMNA-NTRK1 claim 7 , TFG-NTRK1 claim 7 , QKI-NTRK2 claim 7 , NACC2-NTRK2 claim 7 , TPR-NTRK1 claim 7 , RABGAP1L-NTRK1 claim 7 , MPRIP-NTRK1 claim 7 , SQSTM1-NTRK1 claim 7 , EML4-NTRK3 claim 7 , and AFAP1-NTRK2.9. The method of claim 8 , wherein the Trk fusion protein is ETV6-NTRK3.10. The method of claim 6 , wherein the dysregulation of a NTRK gene claim 6 , a Trk protein claim 6 , or expression or activity of the same is one or more point mutations in the gene.11. The method of claim 10 , wherein the one or more point mutations in the gene result in (i) translation of a TrkA protein have one or more amino acid substitutions selected from the group consisting of C6773T claim 10 , C7232T claim 10 , C7301T claim 10 , R33W claim 10 , A336E claim 10 , A337T claim 10 , R324Q claim 10 , R324W claim 10 , V420M claim 10 , R444Q claim 10 , R444W claim 10 , G517R claim 10 , G517V claim 10 , K538A claim 10 , V573M claim 10 , F589L claim 10 , G595R claim 10 , G667C claim 10 , F598L claim 10 , R649W claim 10 , R649L claim 10 , R682S claim 10 , V683G claim 10 , R702C claim 10 , Q627X claim 10 , Q597X claim 10 , and Q633X; (ii) translation of a TrkB protein having one or more amino acid substitutions selected from the group consisting of A13T claim 10 , E142K claim 10 , R136H claim 10 , V619M claim 10 , F633L claim 10 , G639R claim 10 , G709C claim 10 , G709A claim 10 , and G709S; and/or (iii) translation of a TrkC protein having one or more amino acid substitutions selected from the group consisting of V603M claim 10 , F617L claim 10 , G623R claim 10 , G696C claim 10 , G696A claim 10 , and G696S.13. The method of claim 12 , wherein sodium citrate includes at least one of sodium citrate monohydrate and sodium citrate dihydrate.14. The method of claim 12 , wherein sodium citrate includes sodium citrate dihydrate.15. The method of claim 12 , wherein the subject is an infant claim 12 , child claim 12 , or adolescent.16. The method of claim 12 , wherein the pediatric cancer is selected from the group consisting of: congenital mesoblastic nephroma claim 12 , Ph-like acute lymphoblastic leukemia claim 12 , infantile fibrosarcoma claim 12 , pediatric high-grade glioma (HGG) claim 12 , diffuse intrinsic pontine gliomas (DIPGs) claim 12 , pediatric papillary thyroid carcinoma claim 12 , soft tissue sarcoma claim 12 , and spindle cell sarcoma.17. The method of claim 12 , wherein the pediatric cancer is associated with or having a dysregulation of a NTRK gene claim 12 , a Trk protein claim 12 , or expression claim 12 , or activity claim 12 , or level of the same.18. The method of claim 17 , wherein the dysregulation of a NTRK gene claim 17 , a Trk protein claim 17 , or expression claim 17 , or activity claim 17 , or level of the same is a chromosome translocation that results in the translation of a Trk fusion protein.19. The method of claim 18 , wherein the Trk fusion protein is selected from the group consisting of ETV6-NTRK3 claim 18 , RET/NTRK1 claim 18 , TPM3-NTRK1 claim 18 , BTBD1-NTRK3 claim 18 , VCL-NTRK2 claim 18 , AGBL4-NTRK2 claim 18 , LMNA-NTRK1 claim 18 , TFG-NTRK1 claim 18 , QKI-NTRK2 claim 18 , NACC2-NTRK2 claim 18 , TPR-NTRK1 claim 18 , RABGAP1L-NTRK1 claim 18 , MPRIP-NTRK1 claim 18 , SQSTM1-NTRK1 claim 18 , EML4-NTRK3 claim 18 , and AFAP1-NTRK2.20. The method of claim 19 , wherein the Trk fusion protein is ETV6-NTRK3.21. The method of claim 17 , wherein the dysregulation of a NTRK gene claim 17 , a Trk protein claim 17 , or expression or activity of the same is one or more point mutations in the gene.22. The method of claim 21 , wherein the one or more point mutations in the gene result in (i) translation of a TrkA protein have one or more amino acid substitutions selected from the group consisting of C6773T claim 21 , C7232T claim 21 , C7301T claim 21 , R33W claim 21 , A336E claim 21 , A337T claim 21 , R324Q claim 21 , R324W claim 21 , V420M claim 21 , R444Q claim 21 , R444W claim 21 , G517R claim 21 , G517V claim 21 , K538A claim 21 , V573M claim 21 , F589L claim 21 , G595R claim 21 , G667C claim 21 , F598L claim 21 , R649W claim 21 , R649L claim 21 , R682S claim 21 , V683G claim 21 , R702C claim 21 , Q627X claim 21 , Q597X claim 21 , and Q633X; (ii) translation of a TrkB protein having one or more amino acid substitutions selected from the group consisting of A13T claim 21 , E142K claim 21 , R136H claim 21 , V619M claim 21 , F633L claim 21 , G639R claim 21 , G709C claim 21 , G709A claim 21 , and G709S; and/or (iii) translation of a TrkC protein having one or more amino acid substitutions selected from the group consisting of V603M claim 21 , F617L claim 21 , G623R claim 21 , G696C claim 21 , G696A claim 21 , and G696S.