Pioneer Hi-Bred International, Inc.

Incyte Corporation

E.i. Dupont De Nemours and Company

E. I. Du Pont Nemours and Co.

Zoetis Whc 2 LLC

Bo Shen

Mitchell Christian Tarczynski

Peizhong Zheng

Wenqing Yao

Liangxing Wu

Changjiang Li

William B Allen

Keith S Lowe

Timothy George Helentjaris

William James Gordon-Kamm

Knut Meyer

Keith Roesler

Gan-Yuan Zhong

Mark E Williams

Jiacheng Zhou

Howard Glenn Damude

Zhongjiang Jia

Liang Lu

Ericka Bermudez

Jingrui Wu

Jeffrey R Schussler

Chunhong He

Mary A Rupe

Rebecca E Cahoon

Anthony John Kinney

Ding-Quan Qian

Xiaozhao Wang

Fenglei Zhang

Zhan-Bin Liu

Jeffrey Habben

Nathan David Coles

Zhan-bin Liu

Naijing Su

Timothy Martin

Benjamin P Weers

Hajime Sakai

Omolayo O Famodu

Yongzhong Wu

Yongchun Pan

Meizhong Xu

Pingli Liu

Tim Fox

Shili Chen

Kevin G Ripp

Leslie T Harvell

Dale F Loussaert

John D Everard

Thomas G Patterson

Olga Nikolaevna Danilevskaya

Qiyan Lin

Osama Suleiman

Joel R Courter

Dengjin Wang

Igor Cunha Oliveira

Kristin Haug Collet

Joseph A Sclafani

Sabine U Epelbaum

Kayla S Flyckt

Laura L Wayne

Yi Li

Stephen M Allen

Carl R Simmons

Marc C Albertsen

Mark Edward Ruppen

Qun Li

Phaik-Eng Sum

Karlene H Butler

Alexander Sokolsky

Bailin Li

Shane E Abbitt

Russell Dushin

Theodore Mitchell Klein

Rudolf Jung

Michael Xia

Jingwei Li

Scott E Nichols

Kai Liu

Jason Arnold Lotvin

Haiyin He

Zhenwu Li

Ping Cai

Yingda Ye

Darren Robert Abbanat

Leah C Konkol

April L Leonard

Shai J Lawit

Evgueni Ananiev

Odd-Arne Olsen

Darren B Gruis

Chongsheng Eric Shi

Subas Sakya

Valerie Sue Bernan

Carlos M La Rota

Todd J Jones

Heather Marie Christensen

Hyeon-Je Cho

Cheng Lu

Igor Cunha De Oliveira

Alan Gordon Sutherland

Mary J Frank

This application relates to processes and intermediates for the preparation of the PD-1/PD-L1 inhibitor (R)-1-((7-cyano-2-(3'-((2-(difluoromethyl)-7-((3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-yl)amino)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carboxylic acid, and salts and crystalline forms thereof, where the PD-1/PD-L1 inhibitor and solid forms and salt forms thereof are useful in the treatment of various diseases including infectious diseases and cancer.

Process for making a PD-1/PD-L1 inhibitor and salts and crystalline forms thereof

Genome edited plants, plant cells, seeds and plant parts of maize are provided where expression levels and/or activities of MADS-box transcription factors are modulated to improve one or more agronomic characteristics such as grain yield. Also provided are compositions comprising polynucleotides encoding polypeptides and guide RNAs targeted to endogenous maize MADS-box proteins including for example, targeted site-directed mutagenesis using CRISPR-associated nucleases. Additionally, various methods of employing the polynucleotides and genetic modifications in plants, such as methods for modulating expression level in a maize plant and methods for increasing yield of a maize plant are also provided herein.

Improving agronomic characteristics in maize by modification of endogenous mads box transcription factors

The compositions and methods disclosed relate to DNA compositions, plant cells, seeds, plant parts that relate to maize plants with increased grain yield trait. Also provided are assays for detecting the presence of the maize DP-202216-6 event based on the DNA sequence of the recombinant construct inserted into the maize genome and the DNA sequences flanking the insertion site. Kits and conditions useful in conducting the assays are provided.

Genes, constructs and maize event DP-202216-6

Soybean seeds with increased protein and having a modified expression or activity of at least one or two HECT E3 ligase polypeptides are provided. Methods for modifying expression or activity of HECT E3 ligase polypeptides and polynucleotides include genome editing to modify the transcription regulatory region or sequence encoding the HECT E3 ligase polypeptides and transformation with recombinant DNA constructs to enhance or suppress expression or activity of the HECT E3 ligase polypeptides. Plants containing the modifications produce seeds with altered composition such as one or more of increased protein, decreased soluble carbohydrate, increased oleic acid, decreased saturated fats such as palmitic and stearic acids, and decreased linoleic or linolenic acid.

Soybean gene and use for modifying seed composition

The present invention relates to processes of preparing PD-1/PD-L1 inhibitor (R)-1-((7-cyano-2-(3'-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthyridin-8-ylamino)-2,2′-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid, or salts thereof, related synthetic intermediates, and salts of the intermediates, where the PD-1/PD-L1 inhibitor is useful in the treatment of various diseases including infectious diseases and cancer.

Process of preparing a PD-1/PD-L1 inhibitor

Provided are compositions comprising polynucleotides encoding polypeptides. Also provided are recombinant DNA constructs, plants, plant cells, seed, grain comprising the polynucleotides, and plants, plant cells, seed, grain comprising a genetic modification at a genomic locus encoding a polypeptide. Additionally, various methods of employing the polynucleotides and genetic modifications in plants, such as methods for modulating expression level in a plant and methods for increasing yield of a plant are also provided herein.

MADS box proteins and improving agronomic characteristics in plants

Soybean plants producing soybean seeds comprising leghemoglobin are produced by modifying the genome of the soybean plant. Soybean plants, soybean seeds and soy protein compositions comprising leghemoglobin are provided. Soybean plants, soybean seeds and soy protein compositions comprising leghemoglobin and additionally one or more of high oleic acid, low linolenic acid, high protein, low stachyose, low raffinose and low protease inhibitors are provided. Protein compositions comprising leghemoglobin, such as soy isolates and concentrates can be made from the soybean seeds. Additionally, methods for generating and using plants, seeds and protein compositions comprising leghemoglobin are disclosed.

Leghemoglobin in soybean

Provided are compositions comprising polynucleotides encoding modified diacylglycerol acyltransferase-1 (DGAT1) polypeptides having improved properties, such as increased enzymatic activity and/or increased stability. Plants, plant cells, seed, grain and comprising the polynucleotides are provided which have one or more of increased fatty acid or protein content. Methods of generating the polynucleotides in plant cells include transformation and genetic modification. Methods of employing the polynucleotides in plants, methods for increasing DGAT1 activity in a plant, and methods for increasing fatty acid content or protein content in a plant are provided.

Modified seed oil content by gene editing

This application relates to processes and intermediates for the preparation of the PD-1/PD-L1 inhibitor (R)-1-((7-cyano-2-(3′-((2-(difluoromethyl)-7-((3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-yl)amino)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carboxylic acid, and salts and crystalline forms thereof, where the PD-1/PD-L1 inhibitor and solid forms and salt forms thereof are useful in the treatment of various diseases including infectious diseases and cancer.

This application relates to solid forms and salt forms of the PD-1/PD-L1 inhibitor 4,4′-(((((2,2′-dichloro-[1,1′-biphenyl]-3,3′-diyl)bis(azanediyl))bis(carbonyl))bis(1-methyl-1,4,6,7-tetrahydro-5H-imidazo[4,5-c]pyridine-2,5-diyl))bis(ethane-2,1-diyl))bis(bicyclo[2.2.1]heptane-1-carboxylic acid), including processes of preparation thereof, where the solid forms and salt forms are useful in the treatment of various diseases including infectious diseases and cancer.

Salts and crystalline forms of a PD-1/PD-L1 inhibitor

The present invention relates to processes of preparing PD-1/PD-L1 inhibitor (R)-1-((7-cyano-2-(3'-(3-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-1,7-naphthyridin-8-ylamino)-2,2&#x2032;-dimethylbiphenyl-3-yl)benzo[d]oxazol-5-yl)methyl)pyrrolidine-3-carboxylic acid, or salts thereof, related synthetic intermediates, and salts of the intermediates, where the PD-1/PD-L1 inhibitor is useful in the treatment of various diseases including infectious diseases and cancer.

Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections. 

Heterocyclic compounds as immunomodulators

Disclosed are compounds of Formula (I'), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections. 

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Johnston, IA, United States of America

Bo Shen