公开(公告)号：US20200330621A1

公开(公告)日：2020-10-22

申请号：US16914563

申请日：2020-06-29

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Paul Sondel ,  Anatoly Pinchuk ,  Zachary Morris ,  Mario Otto ,  Bryan Bednarz ,  Peter Carlson

IPC: A61K51/04 ,  A61K39/395 ,  A61K9/00 ,  A61K38/20 ,  C07K16/30

Abstract: The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid metal chelate compound that is differentially retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or by performing another method of in situ tumor vaccination. In a non-limiting example, the radioactive phospholipid metal chelate compound has the formula: wherein R1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R2 is —N+(CH3)3.

公开(公告)号：US10736949B2

公开(公告)日：2020-08-11

申请号：US15652400

申请日：2017-07-18

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Paul M. Sondel ,  Anatoly Pinchuk ,  Zachary Morris ,  Mario Otto ,  Bryan Bednarz

IPC: A61K39/00 ,  A61K39/395 ,  A61K39/39 ,  A61K51/04

Abstract: A method of treating a malignant solid tumor in a subject is disclosed herein. The method includes the steps of administering to the subject an immunomodulatory dose of a radiohalogenated compound that is differentially taken up by and retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by intratumorally injecting into (or treating via a separate method) at least one of the malignant solid tumors a composition that includes one or more agents capable of stimulating specific immune cells within the tumor microenvironment. In certain exemplary embodiments, the radiohalogenated compound has the formula: wherein R1 is a radioactive halogen isotope, n is 18 and R2 is —N+(CH3)3.

公开(公告)号：US20180021461A1

公开(公告)日：2018-01-25

申请号：US15658535

申请日：2017-07-25

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Paul Sondel ,  Anatoly Pinchuk ,  Zachary Morris ,  Mario Otto ,  Bryan Bednarz ,  Peter Carlson

IPC: A61K51/04 ,  C07K16/30 ,  A61K38/20 ,  A61K9/00

Abstract: The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid metal chelate compound that is differentially retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or by performing another method of in situ tumor vaccination. In a non-limiting example, the radioactive phospholipid metal chelate compound has the formula: wherein R1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half life of greater than 6 hours and less than 30 days. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R2 is —N+(CH3)3.

公开(公告)号：US20180015154A1

公开(公告)日：2018-01-18

申请号：US15652400

申请日：2017-07-18

Applicant: Wisconsin Alumni Research Foundation

Inventor： Jamey Weichert ,  Paul M. Sondel ,  Anatoly Pinchuk ,  Zachary Morris ,  Mario Otto ,  Bryan Bednarz

IPC: A61K39/00 ,  A61K51/04

Abstract: A method of treating a malignant solid tumor in a subject is disclosed herein. The method includes the steps of administering to the subject an immunomodulatory dose of a radiohalogenated compound that is differentially taken up by and retained within malignant solid tumor tissue, and performing in situ tumor vaccination in the subject by intratumorally injecting into (or treating via a separate method) at least one of the malignant solid tumors a composition that includes one or more agents capable of stimulating specific immune cells within the tumor microenvironment. In certain exemplary embodiments, the radiohalogenated compound has the formula: wherein R1 is a radioactive halogen isotope, n is 18 and R2 is —N+(CH3)3.

公开(公告)号：US20170128572A1

公开(公告)日：2017-05-11

申请号：US15343580

申请日：2016-11-04

Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATION

Inventor： Jamey Weichert ,  Anatoly Pinchuk ,  Wolfgang Axel Tomé

IPC: A61K41/00 ,  A61N5/10 ,  G01N33/60 ,  C07F9/10 ,  A61K51/04

CPC classification number: A61K41/009 ,  A61K49/085 ,  A61K49/10 ,  A61K49/106 ,  A61K51/0482 ,  A61K2039/505 ,  A61N5/1039 ,  A61N5/1048 ,  A61N5/1077 ,  A61N2005/109 ,  C07F9/091 ,  C07F9/10 ,  C07F9/11 ,  C07F9/6515 ,  C07F9/6524 ,  C07F9/6561 ,  G01N33/574 ,  G01N33/58 ,  G01N33/60 ,  G01N2458/15

Abstract: Alkylphosphocholine analogs incorporating a chelating moiety that is chelated to gadolinium are disclosed herein. The alkylphophocholine analogs are compounds having the formula: or a salt thereof. R1 includes a chelating agent that is chelated to a gadolinium atom; a is 0 or 1; n is an integer from 12 to 30; m is 0 or 1; Y is —H, —OH, —COOH, —COOX, —OCOX, or —OX, wherein X is an alkyl or an arylalkyl; R2 is —N+H3, —N+H2Z, —N+HZ2, or —N+Z3, wherein each Z is independently an alkyl or an aroalkyl; and b is 1 or 2. The compounds can be used to detect solid tumors or to treat solid tumors. In detection/imaging applications, the gadolinium emits signals that are detectable using magnetic resonance imaging. In therapeutic treatment, the gadolinium emits tumor-targeting charged particles when exposed to epithermal neutrons.