Abstract: The subject invention pertains to a modified lantibiotic containing an intact cysteine at the C-terminus, particularly, a cysteine that is not decarboxylated and that contains a free carboxyl group. Derivatives of the modified lantibiotic comprising a moiety conjugated to the carboxyl group of the terminal cysteine are also provided. A bacterium that produces a modified lantibiotic having an intact cysteine at the C-terminus are also provided, wherein the bacterium is genetically modified to inactivate a gene that encodes a decarboxylase enzyme that decarboxylates the cysteine at the C-terminus of a precursor lantibiotic. Methods of producing a modified lantibiotic having an intact cysteine at the C-terminus by culturing a bacterium that synthesizes the modified lantibiotic and purifying the lantibiotic are also provided. Mutants of lantibiotics, particularly, mutacin 1140 having higher anti-bacterial activity or higher bacterial expression compared to mutacin 1140 are also provided.
Abstract: The present invention relates to a composition for preventing, improving, or treating aging, wherein the composition comprises a recombinant protein of flagellin, which is the constituent of Vibrio vulnificus flagella, fused with a pathogenic protein antigen, as an active component. According to the present invention, the recombinant protein of the present invention can improve external and internal aging-related malfunctions and enhance immunity. Also, the composition of the present invention can easily perform immunization through mucosal administration.
Type:
Application
Filed:
November 2, 2017
Publication date:
May 3, 2018
Inventors:
Kyung A. CHO, Jae Sung LIM, Joon Haeng RHEE
Abstract: Methods and compositions used to identify and characterize a new class of rhodopsins derived from algae, which are highly sensitive and efficient anion-conducting channelrhodopsins. The rhodopsin domain of these anion-conducting channelrhodopsins have been cloned and expressed in mammalian systems and thus may be used in, among others, optogenetic applications and as therapeutic agents for electrically active cell mediated disorders.
Type:
Application
Filed:
March 18, 2016
Publication date:
May 3, 2018
Applicant:
Board of Regents of the University of Texas System
Inventors:
John Lee SPUDICH, Elena G. GOVORUNOVA, Oleg A. SINESHCHEKOV
Abstract: The present invention is directed to enzyme based methods for removing water insoluble non-starch polysaccharides (NSPs) and/or water soluble or insoluble oligosaccharides from soy products without significantly damaging the proteins contained therein This removal is facilitated by the enzymatic hydrolysis of poly- and oligomeric carbohydrates into monosaccharides and other water soluble sugars. The present invention provides for the production of three streams of useful materials. The first is an enriched protein material comparable to the known SPCs but without significant quantities of undigestible oligosaccharides and polysaccharides. The second is an SPI made from the soluble protein in the hydrolysate which is valuable for high-quality feed, food and industrial uses. The third is the soluble saccharides and hydrolyzed carbohydrates (releasing sugars) that can be converted by fermentation to various valuable bioproducts.
Type:
Application
Filed:
October 18, 2017
Publication date:
May 3, 2018
Applicant:
THE UNIVERSITY OF AKRON
Inventors:
Lu-Kwang JU, Abdullah Loman, Anthony Coffman, Qian Li, Srujana Koganti
Abstract: The present invention provides a dendritic cell modulatory protein which modulates, and preferably inhibits, the differentiation and/or maturation of mammalian dendritic cells. The invention also provides proteins comprising conserved motifs found in such proteins as well as pharmaceutical compositions comprising the dendritic cell modulatory protein and homologues and active fragments thereof, antibodies thereto and methods of treatment which utilise such proteins, homologues, fragments and anti-bodies.
Abstract: It has been believed that promoting the assembly of polysomes composed of many ribosomes attached to mRNA is very effective for highly efficient protein synthesis. However, the mechanism for p180 protein's capability of promoting polysome formation has been yet to be elucidated. The inventors of the present application newly discovered SF3b4 protein as a protein that specifically interacts with the coiled-coil domain of p180 protein, a responsible region for its capability of promoting polysome formation, and which is capable of promoting mRNA localization to an endoplasmic reticulum (ER). The inventors also found that, in cells capable of highly expressing both p180 protein and a protein promoting mRNA localization to an endoplasmic reticulum (ER) (e.g., SF3b4 protein), the mRNA localization to the endoplasmic reticulum can be significantly elevated so that the secretory capacity in cultured cells can be enhanced.
Abstract: The present invention relates to use of an antagonist of BIR1 (B cell immunoglobulin receptor 1) related to the present invention, a method for screening the antagonist, in addition to subtype polypeptides of BIR1, the polynucleotide encoding them and antibodies for the polypeptides. BIR1 functions as an immunosuppressive receptor, and the antagonist of BIR1 has immunopotentive activity, which is able to use for preventing and/or treating a cancer, an immunodeficiency disease or an infectious disease.
Type:
Application
Filed:
November 22, 2017
Publication date:
May 3, 2018
Applicant:
ONO PHARMACEUTICAL CO., LTD.
Inventors:
Tomoyuki ODANI, Hideaki TADA, Kimiho YAMADA
Abstract: The invention concerns a variant (double mutant form) of the survivin polypeptide; nucleic acid molecules encoding the survivin variant; antigen presenting cells (APCs) such as dendritic cells, or APC precursors, comprising the variant survivin polypeptide or encoding nucleic acid sequence; and methods for treating a malignancy, such as myeloma, or for inducing an immune response, utilizing a variant survivin polypeptide, nucleic acid molecule, or APC.
Type:
Application
Filed:
May 7, 2016
Publication date:
May 3, 2018
Inventors:
FREDERICK L. LOCKE, DARIO ALTIERI, SCOTT ANTONIA, CLAUDIO ANASETTI, DMITRY GABRILOVICH
Abstract: The purpose of the present invention is to provide a method for producing a very stable, cyclized mutant protein such that high cyclization efficiency is achieved while the number of amino acids added is minimal and the biological properties of an original protein are maintained. In view of conformational information about the original protein, secondary structure-free regions at N/C terminal portions are deleted. Then, a protein database is screened for proteins with secondary structures similar to those of N/C terminal residues of a secondary structure-forming portion after the deletion. The screening results are used to determine the amino acid length of a loop structure through which the N-terminus and the C-terminus of the secondary structure-forming portion of the original protein are to be connected. A cyclized mutant protein is finally produced having a loop structure with the determined amino acid length.
Abstract: The present invention relates a method of preparing a Glucagon-like peptide 2 (GLP-2) analog by gene recombination. The present invention provides an expression vector, which includes: (a) a nucleic acid sequence encoding tag protein; (b) a nucleic acid sequence encoding Smt3 protein (SEQ ID NO: 1); and (c) a nucleic acid sequence encoding linker peptide (SEQ ID NO: 2) and GLP-2 analog. The fusion protein expressed by the expression vector can be cleaved by thrombin, wherein the cleaving position is at the linker peptide, and then the GLP-2 analog is produced.
Abstract: Disclosed are compositions and methods for detecting, isolating, and/or characterizing a T cell or autoantibody associated with type I diabetes. The composition and methods comprise the use of a hybrid insulin peptide having an N-terminal amino acid sequence taken from the human insulin peptide and a C-terminal amino acid sequence taken from a secretory granule protein that are joined through a peptide bond to form an autoimmune antigen. The detecting, isolating and characterization step further includes performing an immunoassay and/or T cell proliferation assay with the disclosed hybrid insulin peptides, where preferably, the immunoassay is an ELISPOT assay.
Abstract: The present invention relates generally to receptor-selective variants of the low-density lipoprotein receptor-associated protein (RAP) and compositions thereof, methods of generating such variants and methods of using such receptor-selective RAP variant compositions for therapeutic purposes.
Abstract: The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target a G-protein coupled receptor (e.g., a G-protein coupled receptor family C group 5 member D (GPRC5D)), and immunoresponsive cells comprising such CARs. The presently disclosed CARs targeting a G-protein coupled receptor (e.g., GPRC5D) have enhanced immune-activating properties, including anti-tumor activity.
Type:
Application
Filed:
June 5, 2017
Publication date:
May 3, 2018
Inventors:
Renier J. Brentjens, Eric L. SMITH, Cheng LIU
Abstract: The present invention provides materials and methods for antagonizing the function of vascular endothelial growth factor receptors, platelet derived growth factor receptors and other receptors, to prevent, inhibit, or ameliorate allograft rejection or arteriosclerosis in organisms that receive an organ transplant.
Type:
Application
Filed:
November 21, 2017
Publication date:
May 3, 2018
Applicant:
VEGENICS PTY LIMITED
Inventors:
Kari Alitalo, Karl B. Lemström, Antti I. Nykänen
Abstract: The present disclosure relates to a class of engineered polypeptides having a binding affinity for the neonatal Fc receptor (in the following referred to as FcRn), and provides an FcRn binding polypeptide comprising the sequence EX2 X3 X4 AX6 X7 EIRWLPNL X16X17 X18 QRX21 AFIX25 X26LX28 X29. The present disclosure also relates to the use of such an FcRn binding polypeptide as an agent for modifying pharmacokinetic and pharmacodynamic properties and as a therapeutic agent.
Type:
Application
Filed:
December 14, 2017
Publication date:
May 3, 2018
Inventors:
Caroline Ekblad, Elin Gunneriusson, Malin Lindborg, Lars Abrahmsen, John Löfblom, Torbjörn Gräslund, Johan Seijsing
Abstract: Disclosed herein are switchable chimeric receptors, switchable chimeric receptor effector cells and chimeric receptor effector cell switches. The switchable chimeric receptor-ECs are generally T cells. The chimeric receptors have non-antibody extracellular domains that recognize a chimeric receptor binding partner on the chimeric receptor-EC switch or target cell. The chimeric receptor-ECs and switches may be used for the treatment of a disease or condition in a subject in need thereof.
Type:
Application
Filed:
March 28, 2016
Publication date:
May 3, 2018
Applicant:
The California Institute for Biomedical Research
Inventors:
Travis YOUNG, Chanhyuk KIM, Peter G. SCHULTZ
Abstract: The present invention provides a modified collagen comprising S-nitroso groups and a method of manufacture of such a modified collagen. Also provided is a wound dressing comprising such a modified collagen, particularly a wound dressing comprising a formulated composition comprising such a modified collagen.
Abstract: Described herein is a new antidote for the rapid elimination of carbon monoxide from hemoglobin, including brain, heart, and red cell hemoglobin. The disclosed therapy involves the use of modified human globins, particularly neuroglobins modified at residue 64 and cytoglobins modified at residue 81, which bind carbon monoxide with extremely high affinity. The monomeric mutant globins are infused into blood, where they rapidly and irreversibly sequester carbon monoxide, and thus limit toxic effects of carbon monoxide on cellular respiration and oxygen transport and utilization.
Type:
Application
Filed:
October 6, 2017
Publication date:
May 3, 2018
Applicant:
University of Pittsburgh - Of the Commonwealth System of Higher Education
Abstract: A method for inactivation or removal of coagulation factors VII, FVII, FVIIa, FIX, FIXa, FX, FXI and FXIa inor from protein containing solutions obtained from blood, blood plasma, plasma fractions or by recombinant means wherein the protein containing solution is contacted with an organic acid or its salt while being stirred.
Type:
Application
Filed:
November 6, 2017
Publication date:
May 3, 2018
Applicant:
OCTAPHARMA AG
Inventors:
Waltraud KAAR, Alfred ZOCHLING, Karin AHRER
Abstract: The present invention provides for a method for improving properties of an antibody such as an expression level and stability. A method for obtaining an antibody with an improved expression level and/or stability by modifying human antibody or a humanized antibody, characterized by that at least any one of the amino acid residues at position 8, 12, 15 or 18 (according to Kabat numbering) in a light chain variable region (hereinafter referred to as “VL chain”) of a human antibody or a humanized antibody is substituted with a different amino acid other than proline or cysteine, and a human antibody or a humanized antibody or a human antibody fragment or a humanized antibody fragment with an improved expression level and/or stability which are obtained by said method.
Abstract: This disclosure provides a multimeric hepatitis B virus (HBV) protein binding molecule, e.g., a dimeric IgA or a pentameric or hexameric IgM binding molecule, comprising at least two bivalent binding units, or variants or fragments thereof, each comprising at least two antibody heavy chain constant regions or fragments thereof, wherein each heavy chain constant region or fragment thereof is associated with an HBV antigen binding domain. The disclosure also provides compositions comprising the multimeric binding molecules, polynucleotides encoding the multimeric binding molecules, and methods to make and use the multimeric binding molecules.
Type:
Application
Filed:
March 25, 2016
Publication date:
May 3, 2018
Inventors:
Stephen F. Carroll, Ramesh Baliga, Dean NG, Bruce A. Keyt
Abstract: The invention provides a construct comprising two or more fusion proteins of Formulas (I)-(IV): A-(optional linker)-C-(optional linker)-B (Formula I), B-(optional linker)-D-(optional linker)-E-(optional linker)-B (Formula II), A-(optional linker)-C (Formula III), and B-(optional linker)-D-(optional linker)-E (Formula IV), wherein A denotes an antibody or antibody fragment, B denotes a single domain CD4, C denotes an immunoglobulin light chain constant region D denotes an immunoglobulin heavy chain constant region, and E denotes an Fc region or a portion thereof that is optionally defucosylated.
Type:
Application
Filed:
December 16, 2015
Publication date:
May 3, 2018
Applicants:
The United States of America, as Represented by the Secretary, Dept. of Health and Human Resources, Fudan University
Inventors:
Dimiter S. Dimitrov, Weizao Chen, Tianlei Ying
Abstract: This disclosure provides a multimeric human immunodeficiency virus (HIV) protein binding molecule, e.g., an dimeric IgA or a pentameric or hexameric IgM binding molecule, comprising at least two bivalent binding units, or variants or fragments thereof, each comprising at least two antibody heavy chain constant regions or fragments thereof, wherein each heavy chain constant region or fragment thereof is associated with an HIV antigen binding domain. Also provided are compositions comprising the multimeric binding molecules, polynucleotides encoding the multimeric binding molecules, and methods to make and use the multimeric binding molecules.
Type:
Application
Filed:
April 15, 2016
Publication date:
May 3, 2018
Inventors:
Bruce Keyt, Dan T. Stinchcomb, Ole A. Olsen
Abstract: The present invention relates, in part, to bispecific antibodies that bind the pertussis toxin protein. The present invention further relates to the use of the bispecific antibodies for the prevention and treatment of Bordetella pertussis infections.
Abstract: Disclosed herein are sensor systems, compositions comprising the sensor systems, and methods of using the same. In particular aspects, disclosed herein are sensor systems for a target intracellular ligand and uses thereof, e.g., in detection assays or in cell manipulation or therapeutic applications.
Type:
Application
Filed:
April 15, 2016
Publication date:
May 3, 2018
Applicant:
PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Inventors:
Chung Yiu Jonathan Tang, Constance Cepko, Eugene Drokhlyansky, Sui Wang
Abstract: Disclosed herein are novel compositions and methods for the treatment of age-related diseases, mitochondrial diseases, the improvement of stress resistance, the improvement of resistance to hypoxia and the extension of life span. Also described herein are methods for the identification of agents useful in the foregoing methods. Methods and compositions are provided for the treatment of diseases or disorders associated with mitochondrial dysfunction.
Type:
Application
Filed:
May 26, 2017
Publication date:
May 3, 2018
Applicants:
President and Fellows of Harvard College, Massachusetts Institute of Technology
Inventors:
David A. Sinclair, Ana P. Gomes, Eric Bell
Abstract: Antibodies which bind and neutralize human IL-33, and methods of using same, are provided, said antibodies are useful as agents for treating conditions associated with allergic disease including treating atopic dermatitis.
Type:
Application
Filed:
October 24, 2017
Publication date:
May 3, 2018
Inventors:
Robert Jan Benschop, Julian Davies, Angela Jeannine Okragly, Chetankumar Natvarlal Patel
Abstract: Multivalent binding peptides, including bi-specific binding peptides, having immunoglobulin effector function are provided, along with encoding nucleic acids, vectors and host cells as well as methods for making such peptides and methods for using such peptides to treat or prevent a variety of diseases, disorders or conditions, as well as to ameliorate at least one symptom associated with such a disease, disorder or condition.
Type:
Application
Filed:
June 8, 2017
Publication date:
May 3, 2018
Applicant:
APTEVO RESEARCH AND DEVELOPMENT LLC
Inventors:
Peter Armstrong THOMPSON, Jeffrey A. LEDBETTER, Martha Susan HAYDEN-LEDBETTER, Laura Sue GROSMAIRE, Robert BADER, William BRADY
Abstract: The present invention is directed to bi-specific monovalent diabodies that comprise two polypeptide chains and which possess at least one binding site specific for an epitope of CD3 and one binding site specific for an epitope of gpA33 (i.e., a “gpA33×CD3 bi-specific monovalent diabody”). The present invention also is directed to bi-specific monovalent diabodies that comprise an immunoglobulin Fc Domain (“bi-specific monovalent Fc diabodies”) and are composed of three polypeptide chains and which possess at least one binding site specific for an epitope of gpA33 and one binding site specific for an epitope of CD3 (i.e., a “gpA33×CD3 bi-specific monovalent Fc diabody”). The bi-specific monovalent diabodies and bi-specific monovalent Fc diabodies of the present invention are capable of simultaneous binding to gpA33 and CD3. The invention is directed to pharmaceutical compositions that contain such bi-specific monovalent diabodies or such bi-specific monovalent Fc diabodies.
Type:
Application
Filed:
November 21, 2017
Publication date:
May 3, 2018
Applicant:
MacroGenics, Inc.
Inventors:
Paul A. Moore, Jonathan Li, Francine Zhifen Chen, Leslie S. Johnson, Kalpana Shah, Ezio Bonvini
Abstract: The present invention relates to agents that modulate the Hippo pathway and Hippo pathway signaling, such as antibodies and soluble receptors, as well as to methods of using the agents for the treatment of diseases such as cancer.
Type:
Application
Filed:
July 6, 2017
Publication date:
May 3, 2018
Applicant:
OnceMed Pharmaceuticals, Inc.
Inventors:
Austin L. GURNEY, Cecile Chartier-Courtaud
Abstract: A pharmaceutical composition comprising an active agent that causes reduction of the level of systemic immunosuppression in an individual for use in treating a disease, disorder, condition or injury of the CNS that does not include the autoimmune neuroinflammatory disease, relapsing-remitting multiple sclerosis (RRMS), is provided. The pharmaceutical composition is for administration by a dosage regimen comprising at least two courses of therapy, each course of therapy comprising in sequence a treatment session followed by an interval session.
Type:
Application
Filed:
November 22, 2017
Publication date:
May 3, 2018
Applicant:
Yeda Research and Development Co. Ltd.
Inventors:
Michal Eisenbach-Schwartz, Kuti Baruch, Neta Rosenzweig
Abstract: The present invention is directed to antibodies, including novel antigen binding domains and heterodimeric antibodies, that bind somatostatin receptor 2 (SSTR2)
Type:
Application
Filed:
June 28, 2017
Publication date:
May 3, 2018
Inventors:
Gregory Moore, Rumana Rashid, Sung-Hyung Lee, Paul Foster
Abstract: The present invention is directed to novel bispecific heterodimeric Fc fusion proteins comprising an IL-15/IL-15R? Fc-fusion protein and a PD-1 antibody fragment-Fc fusion protein.
Type:
Application
Filed:
October 16, 2017
Publication date:
May 3, 2018
Inventors:
Matthew Bernett, Rumana Rashid, John Desjarlais, Rajat Varma, Christine Bonzon
Abstract: Provided herein are various embodiments relating to antibodies. Some of the embodiments include antagonist antibodies that bind PD-1. Such antibodies can be used in methods to treat, for example, cancer.
Type:
Application
Filed:
November 1, 2017
Publication date:
May 3, 2018
Applicant:
Jounce Therapeutics, Inc.
Inventors:
George Robert Mabry, III, Stephen Sazinsky
Abstract: Antibodies that bind specifically to glycosylated PD-L1 relative to unglycosylated PD-L1 are provided. Antibodies that recognize specific epitopes of glycosylated PD-L1 protein and can block the binding of PD-L1 to PD-1 are provided. In some aspects, PD-L1 polypeptides comprising glycosylated amino acid residues at amino and carboxy terminal positions of the PD-L1 extracellular domain are also provided. Methods for making and using such antibodies and polypeptides (e.g., for the treatment of cancer) are also provided.
Type:
Application
Filed:
March 29, 2016
Publication date:
May 3, 2018
Applicants:
STCUBE, INC., BOARD OF REGENTS, THE UNIVERSITY OF TEXAS
Inventors:
Stephen S. YOO, Ezra M. CHUNG, Yong-Soo KIM, Mien-Chie HUNG, Chia-Wei LI, Seung-Oe LIM
Abstract: CAR cells and antibodies targeting human B7-H4 expressed on many human cancers including but not limited to breast ovarian, and renal cancers are described as a new method of cancer treatment. It is proposed that B7-H4 CAR cells are safe and effective in patients and can be used to treat human tumors expressing the B7-H4 surface protein.
Abstract: This invention relates generally to a combination therapy for the treatment of cancer, particularly to a combination of (i) a bifunctional molecule comprising a TGF?RII or fragment thereof capable of binding TGF? and an antibody, or antigen binding fragment thereof, that binds to an immune checkpoint protein, such as Programmed Death Ligand 1 (PD-L1) and (ii) at least one additional anti-cancer therapeutic agent.
Abstract: The present invention generally relates to antibodies specific for asialoglycoprotein receptor (ASGPR) and their use for selectively delivering effector moieties that influence cellular activity. In addition, the present invention relates to polynucleotides encoding such antibodies, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the antibodies of the invention, and to methods of using them in the treatment of disease.
Type:
Application
Filed:
September 21, 2017
Publication date:
May 3, 2018
Applicant:
ROCHE GLYCART AG
Inventors:
Thomas HOFER, Changhua Ji, Ekkehard Moessner, Pablo Umana
Abstract: The invention provides compositions and methods for treating diseases associated with expression of a tumor antigen as described herein. The invention also relates to nucleic acids comprising a truncated PGK promoter operably linked to a chimeric antigen receptor (CAR) specific to a tumor antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a tumor antigen as described herein.
Type:
Application
Filed:
January 15, 2016
Publication date:
May 3, 2018
Inventors:
Jennifer Brogdon, Hilmar Erhard Ebersbach, David Glass, Thomas Huber, Julia Jascur, Carl H. June, Jihyun Lee, Joan Mannick, Michael C. Milone, Leon Murphy, Avery D. Posey, Huijuan Song, Yongqiang Wang, Lai Wei, Qilong Wu, Qiumei Yang, Jiquan Zhang
Abstract: This application provides: an antibody which specifically binds to an ALK2 protein and has an activity of inhibiting BMP signal transduction mediated by ALK2; a method for producing the antibody; and a pharmaceutical composition comprising the antibody, for treating and/or preventing ectopic ossification and/or bone dysplasia, anemia, or diffuse intrinsic pontine glioma (DIPG).
Type:
Application
Filed:
January 29, 2016
Publication date:
May 3, 2018
Applicants:
Saitama Medical University, Daiichi Sankyo Company, Limited
Abstract: The invention relates to anti-HER3/HER4 antigen binding proteins, e.g. anti-HER3/HER4 antibodies, that bind to the beta-hairpin of HER3 and the beta-hairpin of HER4, methods for selecting these antigen binding proteins, their preparation and use as medicament.
Type:
Application
Filed:
August 3, 2017
Publication date:
May 3, 2018
Applicant:
Hoffmann-La Roche Inc.
Inventors:
Birgit Bossenmaier, Guy Georges, Michael Gerg, Gerhard Niederfellner, Christian Scholz, Michael Schraeml
Abstract: CAR cells targeting FLT3 relevant antigens are described as a new method of cancer treatment. It is proposed that FLT3 CAR cells are safe and effective in patients and can be used to treat human tumors and cancer.
Type:
Application
Filed:
November 13, 2017
Publication date:
May 3, 2018
Applicant:
Precision Immunotherapy, Inc.
Inventors:
Jianhua Yu, Michael Caligiuri, Steven Devine
Abstract: The invention provides anti-IFNAR1 antibodies with reduced affinity for Fc receptors and/or ligands and methods of making and using such antibodies.
Type:
Application
Filed:
September 21, 2017
Publication date:
May 3, 2018
Inventors:
ANTHONY COYLE, PETER KIENER, HERREN WU, RICARDO CIBOTTI
Abstract: Bispecific antibody compounds, and methods of using same, are provided which bind and neutralize Dkk-1 and RANKL and which are useful as adjuncts to spinal fusion surgery or as agents for bone healing or treating conditions associated with bone loss or degeneration.