Macrogenics, Inc.

Cognis Corporation

Jeffrey B Stavenhagen

Christopher Rankin

Sergey Gorlatov

Sujata Vijh

Ling Ling Huang

Scott Koenig

Nadine Tuaillon

David L Craft

C Ron Wilson

Yeyan Zhang

The present invention relates to methods of treating or preventing cancer and other diseases using molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds an Fc&#x3b3;R that activates a cellular effector ('Fc&#x3b3;R,' such as Fc&#x3b3;RIIA or Fc&#x3b3;RIIIA) and an Fc&#x3b3;R that inhibits a cellular effector ('Fc&#x3b3;R,' such as Fc&#x3b3;RIIA) with an altered Ratio of Affinities relative to the respective binding affinities of such Fc&#x3b3;R for the Fc region of the wild-type immunoglobulin. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by Fc&#x3b3;R is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by Fc&#x3b3;R is desired (e.g., inflammation, autoimmune disease).

Methods for the treatment of disease using immunoglobulins having fc regions with altered affinities for FcgammaRactivating and FegammaRinhibiting

Methods for the treatment of disease using immunoglobulins having Fc regions with altered affinities for Fc&#x3b3;Rand Fc&#x3b3;R

The present invention relates to methods of treating or preventing cancer and other diseases using molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds an Fc&#x3b3;R that activates a cellular effector ('Fc&#x3b3;R,' such as Fc&#x3b3;RIIA or Fc&#x3b3;RIIIA) and an Fc&#x3b3;R that inhibits a cellular effector ('Fc&#x3b3;R,' such as Fc&#x3b3;RIIA) with an altered Ratio of Affinities relative to the respective binding affinities of such Fc&#x3b3;R for the Fc region of the wild-type immunoglobulin. The methods of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where either an enhanced efficacy of effector cell function mediated by Fc&#x3b3;R is desired (e.g., cancer, infectious disease) or an inhibited effector cell response mediated by Fc&#x3b3;R is desired (e.g., inflammation, autoimmunde disease).

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The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds Fc&#x3b3;RIIIA and/or Fc&#x3b3;RIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by Fc&#x3b3;R is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

Identification and engineering of antibodies with variant FC regions and methods of using same

Identification and engineering of antibodies with variant Fc regions and methods of using same

The present invention relates to molecules comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds Fc&#x3b3;RIIIA and/or Fc&#x3b3;RIIA with a greater affinity relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are useful in preventing, treating, or ameliorating symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function mediated by Fc&#x3b3;R is desired, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

The present invention relates to molecules having a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region. These modified molecules confer an effector function to a molecule, where the parent molecule does not detectably exhibit this effector function. In particular, the molecules of the invention have an increased effector cell function mediated by a Fc&#x3b3;R, such as, but not limited to, ADCC. In one embodiment, the variant Fc region binds Fc&#x3b3;RIIIA and/or Fc&#x3b3;RIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention have particular utility in treatment, prevention or management of a disease or disorder, such as cancer, in a sub-population of patients, wherein the target antigen is expressed at low levels in the target cell population, in particular, in patients refractory to treatment with an existing therapeutic antibody due to the low level of target antigen expression on the cancer or associated cells.

Engineering Fc antibody regions to confer effector function

The present invention provides modified promoters fromCYP and POX4 genes. The modified promoters have various sequence motifs added, deleted, or altered in order to modulate expression of a coding sequence operably linked thereto. The sequence motifs comprise repressors of gene induction (URS sequences) and activators of gene induction (UAS sequences) as well as oleic acid response elements (ORE sequences). Yeast host cells comprising such modified promoters are also provided. Methods of altering expression of a protein of the beta or omega oxidation pathways using a subject modified promoter are also provided.

The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds Fc&#x3b3;RIIA and/or Fc&#x3b3;RIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by Fc&#x3b3;R is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

Growing community of inventors

Brookeville, MD, United States of America

Jeffrey B Stavenhagen