公开(公告)号：US11613514B2

公开(公告)日：2023-03-28

申请号：US17155162

申请日：2021-01-22

申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  University of Maryland, Baltimore

发明人： Craig Thomas ,  Carlos Zarate ,  Ruin Moaddel ,  Todd Gould ,  Panos Zanos ,  Patrick Morris

IPC分类号： C07C225/20 ,  C07C221/00 ,  C07C269/06

摘要： The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

公开(公告)号：US10919842B2

公开(公告)日：2021-02-16

申请号：US16088371

申请日：2017-03-27

申请人： The United States of America, As Represented by the Secretary, Department of Health and Human Services ,  University of Maryland

发明人： Craig Thomas ,  Carlos Zarate ,  Ruin Moaddel ,  Todd Gould ,  Panos Zanos ,  Patrick Morris

IPC分类号： C07C225/20 ,  C07C221/00 ,  C07C269/06

摘要： The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

公开(公告)号：US20230192594A1

公开(公告)日：2023-06-22

申请号：US18170048

申请日：2023-02-16

申请人： The United States of America, as Represented by the Secretary, Department of Health ,  University of Maryland, Baltimore

发明人： Craig Thomas ,  Carlos Zarate ,  Ruin Moaddel ,  Todd Gould ,  Panos Zanos ,  Patrick Morris

IPC分类号： C07C225/20 ,  C07C221/00 ,  C07C269/06

CPC分类号： C07C225/20 ,  C07C221/00 ,  C07C269/06 ,  C07B2200/13 ,  C07C2601/14 ,  C07C2601/16

摘要： The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketam-ine (HNK) includes preparation of (R)-norket-amine via chiral resolution from racemic norketamine via a chiral resolution with L-pyro-glutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hy-droxynorketamine hydrochloride salts.

公开(公告)号：US20150299791A1

公开(公告)日：2015-10-22

申请号：US14439468

申请日：2013-11-04

申请人： THE JOHNS HOPKINS UNIVERSITY ,  UNIVERSITY OF MARYLAND

发明人： Zachary Kaminsky ,  Jennifer L. Payne ,  Todd Gould

IPC分类号： C12Q1/68 ,  G06F19/00 ,  G01N15/10

CPC分类号： C12Q1/6883 ,  C12Q2600/118 ,  C12Q2600/154 ,  C12Q2600/158 ,  C12Q2600/16 ,  G01N15/10 ,  G01N2015/008 ,  G01N2015/1062 ,  G16H50/30

摘要： The present invention relates to the field of post-partum depression. More specifically, the present invention relates to the use of biomarkers to diagnose post-partum depression or predict a risk thereof. In a specific embodiment, a method for identifying a likelihood of PPD in a patient comprises the steps of (a) providing a sample from the patient; (b) measuring white blood cell type counts and DNA methylation levels of a panel of biomarkers in the sample collected from the patient, wherein the panel of biomarkers comprises HP1BP3 and TTC9B and the white blood cell type counts comprise monocytes and non-monocytes; and (c) identifying the patient as likely to develop PPD based on the relative DNA methylation levels at the biomarker loci relative to the ratio of monocytes:non-monocytes.

摘要翻译： 本发明涉及产后抑郁症领域。 更具体地，本发明涉及生物标志物诊断产后抑郁症或预测其风险的用途。 在具体实施方案中，用于鉴定患者中PPD可能性的方法包括以下步骤：（a）从患者提供样品; （b）测量从患者收集的样品中的一组生物标志物的白细胞类型计数和DNA甲基化水平，其中生物标志物组包括HP1BP3和TTC9B，白细胞类型计数包括单核细胞和非单核细胞; 基于相对于单核细胞比例的生物标记基因座的相对DNA甲基化水平，鉴定患者可能开发PPD：非单核细胞。

公开(公告)号：US20230151423A9

公开(公告)日：2023-05-18

申请号：US16990572

申请日：2020-08-11

申请人： THE JOHNS HOPKINS UNIVERSITY ,  UNIVERSITY OF MARYLAND

发明人： Zachary Kaminsky ,  Jennifer L. Payne ,  Todd Gould

IPC分类号： C12Q1/6883 ,  G16H50/30

CPC分类号： C12Q1/6883 ,  G16H50/30 ,  C12Q2600/118 ,  C12Q2600/154 ,  C12Q2600/158 ,  C12Q2600/16

摘要： The present invention relates to the field of post-partum depression. More specifically, the present invention relates to the use of biomarkers to diagnose post-partum depression or predict a risk thereof. In a specific embodiment, a method for identifying a likelihood of PPD in a patient comprises the steps of (a) providing a sample from the patient; (b) measuring white blood cell type counts and DNA methylation levels of a panel of biomarkers in the sample collected from the patient, wherein the panel of biomarkers comprises HP1BP3 and TTC9B and the white blood cell type counts comprise monocytes and non-monocytes; and (c) identifying the patient as likely to develop PPD based on the relative DNA methylation levels at the biomarker loci relative to the ratio of monocytes:non-monocytes.

公开(公告)号：US20230022767A1

公开(公告)日：2023-01-26

申请号：US17777654

申请日：2020-11-17

申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVIC ,  THE UNIVERSITY OF MARYLAND, BALTIMORE

发明人： Patrick Joseph Morris ,  Craig Joseph Thomas ,  Stephen J. Byard ,  Martin P. Wilmshurst ,  Todd Gould ,  Carlos Zarate ,  Ruin Moaddel

IPC分类号： C07C225/20

摘要： The disclosure provides salts of (2R,6R)-hydroxynorketamine (HNK), wherein the salt is with an organic acid chosen from malonic acid, salicylic acid, ethane sulfonic acid, glycolic acid, stearic acid, or capric acid, and their crystal forms.

公开(公告)号：US20190135732A1

公开(公告)日：2019-05-09

申请号：US16088371

申请日：2017-03-27

申请人： The United States of America, As Represented by the Secretary, Department of Health and Human Serv ,  University of Maryland

发明人： Craig Thomas ,  Carlos Zarate ,  Ruin Moaddel ,  Todd Gould ,  Panos Zanos ,  Patrick Morris

IPC分类号： C07C225/20 ,  C07C221/00

摘要： The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

公开(公告)号：US20190083420A1

公开(公告)日：2019-03-21

申请号：US16088294

申请日：2017-03-27

申请人： The Uinited States of America, as represented by the Secretary, Department of Health and Human Serv ,  University of Maryland

发明人： Irving Wainer ,  Carlos Zarate ,  Ruin Moaddel ,  Todd Gould ,  Panos Zanos ,  Craig Thomas ,  Patrick Morris

IPC分类号： A61K31/135 ,  A61P25/24

摘要： Disclosed is a method of treating Psychotic Depression, Suicidal Ideation, Disruptive Mood Dysregulation Disorder, Persistent Depressive Disorder (Dysthymia), Premenstrual Dysphoric Disorder, Substance/Medication-Induced Depressive Disorder, Depressive Disorder Due to Another Medical Condition, Other Specified Depressive Disorder, Unspecified Depressive Disorder, Separation Anxiety Disorder, Selective Mutism, Specific Phobia, Social Anxiety Disorder (Social Phobia), Panic Disorder, Panic Attack (Specifier), Agoraphobia, Generalized Anxiety Disorder, Substance/Medication-Induced Anxiety Disorder, Anxiety Disorder Due to Another Medical, Other Specified Anxiety Disorder, Unspecified Anxiety Disorder, or fatigue the method including administering a pharmaceutical composition containing an effective amount of an active agent, wherein the active agent is purified (2R,6R)-hydroxynorketamine, purified (2S,6S)-hydroxynorketamine, or a combination thereof, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier to a patient in need of such treatment.