Alderbio Holdings LLC

US Government As Represented by the Secretary of the Army

H. Lundbeck A/s

Alder Biopharmaceuticals, Inc.

Mark Young

Gary Lesnicki

Patricia Dianne McNeill

Franz Hartner

John A Latham

Leon F Garcia-Martinez

Ethan Wayne Ojala

Daniel S Allison

Leon Manole

Anthony P Farina

Geoffrey F Lee

Steven D Davin

Hoa Binh Do

Stewart Gilman

John J Dineen

Leon F Garcia-martinez

William Rice

Frank Renner

Anthony Farina

Methods for producing heterologous proteins are disclosed. In particular, the present disclosure provides improved methods of producing desired proteins, including multi-subunit proteins such as antibodies, with a higher yield and improved purity. In exemplary embodiments, the transformed cells are a yeast, e.g., methylotrophic yeast such as

Temperature shift for high yield expression of polypeptides in yeast and other transformed cells

A feedback control mechanism for a fermentation of yeast cells to make recombinant proteins uses a respiratory quotient measurement which adjusts the levels of oxygenation and/or fermentable sugar feed. The feedback control mechanism permits well controlled cultures that produce good amounts of product while avoiding toxic accumulation of ethanol. Additionally, recombinant proteins so produced have excellent qualitative properties, such as excellent homogeneity and proper inter-subunit assembly.

Fermentation process for antibody production

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Processes for producing and purifying recombinant proteins are disclosed. In particular, the present disclosure provides processes of producing and purifying multi-subunit proteins expressed in yeast or filamentous fungal cells. The production and/or purification of such proteins are monitored for impurities, preferably using lectin binding assays, such that one or more process parameters may be adjusted to maximize the amount of desired recombinant protein and minimize the amount of glycosylated impurities. The processes can also be monitored for other undesired product-associated impurities, such as aggregates and nucleic acids. In exemplary embodiments, the recombinant proteins are multi-subunit proteins, such as antibodies, the host cell is a yeast, such as, and the glycosylated impurity is a glycovariant of the desired recombinant polypeptide, such as an N-linked and/or O-linked glycovariant.

Antibody purification and purity monitoring

A stacked, collaborative engagement ammunition round is presented. The round includes plural stacked miniaturized projectiles where such projectiles separate after launch and then swarm as a group towards a target or targets. At launch, the projectiles may fly in a preselected formation, leader-follower towards the target. Or, the projectiles may deploy propellers, tri-copter or quad-copter vanes, and self steer swarming to the target. Each projectile has its own miniaturized guidance, navigation and control components, autopilot, cameras, transmitter, receiver, antennae, power source, sensors, fuzes and/or flex circuits.

Stackable collaborative engagement munition

An aerodynamic device, such as a projectile includes an elongated forebody, and an aft section secured to the forebody. The aft section acts as a d control device, and includes a connecting member that extends integrally in a conically shaped flared section, for generating a lift force to help stabilize the projectile during forward flight. The aft section further includes a flange that extends from the flared section, and that provides velocity decay and optimal drag, in order to limit the projectile flight and descent within a predetermined safety or emergency range. The flared section is defined between an innermost edge positioned adjacent to the connecting member, and an outermost edge positioned adjacent to the flange. The flange includes a forward facing wall that extends from the outermost edge and that has a height 'H' that controls the amount of drag on the projectile, such that the outer diameter of the aft section is less than, or equal to the inner diameter of the gun barrel from which the projectile is fired.

Training projectile

The disclosure is of a projectile having a main body, a nose and a tail iuding a flared tail member, the projectile having its center of gravity close to the nose thereof.

Growing community of inventors

Boulder, CO, United States of America

Mark Young