CN1289253A - Treating atopic dermatitis with lgE antagonists - Google Patents
Treating atopic dermatitis with lgE antagonists Download PDFInfo
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- CN1289253A CN1289253A CN99802505A CN99802505A CN1289253A CN 1289253 A CN1289253 A CN 1289253A CN 99802505 A CN99802505 A CN 99802505A CN 99802505 A CN99802505 A CN 99802505A CN 1289253 A CN1289253 A CN 1289253A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/42—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins
- C07K16/4283—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig
- C07K16/4291—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an allotypic or isotypic determinant on Ig against IgE
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
Abstract
The invention relates to a pharmaceutical composition for treatment of atopic dermatitis comprising a suitable IgE antagonist which does not induce release of the mediators of allergy; for example, anti-IgE antibodies which bind to secreted IgE, to membrane IgE on the surface of IgE-producing B cells, but not to IgE bound to the Fc epsilon RI on the surface of basophils or mast cells. Preferably, these antibodies also do not bind to IgE bound to Fc epsilon RII receptors. It is also preferable if these antibodies have human IgG1 or IgG3 constant regions, as well as further human portions, if desired. The pharmaceutical composition can be administered systemically or topically.
Description
Background of invention
IgE (IgE) is an immunoglobulin like protein (or title " antibody ") molecule.IgE exists concentration low than the immunoglobulin of other kinds such as IgG, IgM, IgA, IgD etc. in human serum.IgE is considered to defend to work in the parasitic invasion and attack at human body, but this effect never is defined as being necessary clearly or or even useful, in developed country, parasitic infection is not a serious problem at least.IgE is as being that the super quick allergic amboceptor of hair style is well-known, and these allergy comprise allergic rhinitis (pollinosis), extrinsic asthma, and food and drug allergy.
In allergy process by the IgE mediation, after IgE is come out by B emiocytosis, partly be attached on the Fc ε R I receptor by its Fc, this receptor is present in the surface of basophil, mastocyte and langerhans' cells.If be attached to IgE on these cell surfaces with allergen contact and combine, can cause these crosslinked in conjunction with the IgE molecule, then make that the receptor under it is also crosslinked thereupon, discharge thereby trigger some pharmacology's amboceptors, described amboceptor is such as histamine, 5-hydroxy tryptamine, leukotriene and hypersensitive slow reacting substance.These amboceptors have caused allergic pathological manifestations.
Some once lived through the patient of the part or all of allergic disease of IgE mediation, also suffered from a kind of dermatosis that is called the misery of atopic dermatitis easily.The feature of atopic dermatitis is the skin lesion of pruritus, erythema and pain.Part chronic dermatitis patient, its skin can lichenization.Though atopic dermatitis usually can occur simultaneously with other allergic disease, do not determine as yet that on one's body infected patient existence is related between the performance of its atopic dermatitis or its seriousness and the IgE content height.The person skilled in art believes that atopic dermatitis is perhaps relevant with IgE, but independent IgE is not the cause of disease material.
Develop the special anti-IgE antibodies of a class and be used for treating allergic disease.These antibodies secretory IgE, but can be in conjunction with attached to the IgE on the Fc ε R I receptor.When these anti-IgE antibodies were administered to inside of human body, their can be in conjunction with IgE and neutralize it, made it can not be again in conjunction with Fc ε R I or Fc ε R II receptor, and the latter is present on B cell or other cell types.These anti-IgE antibodies also can be in conjunction with attached to the IgE on the cell membrane of the B cell that generates IgE (claiming " film conjunction type IgE ").After on these antibodies, can further help to reduce or eliminate the B cell of generation IgE by the cytotoxicity (" ADCC ") of dependence antibody or the cytolysis of complement-mediated, and therefore reduce the content of secretory IgE.But, because they are not in conjunction with attached to the IgE on the Fc ε R I, therefore can not cause crosslinkedly, they itself also can not cause the release of allergic pharmacology's amboceptor.
Shown that in animal model and human clinical trial this type of anti-IgE antibodies can reduce IgE content (referring to Corne etc., " clinical examination magazine " 99, No.5,879-887,1997).This type of anti-IgE antibodies also shows the effect with treatment allergic rhinitis and extrinsic asthma in several human clinical trials, as reduced IgE content in body true desired by it.(, the same referring to Corne etc.; Boulet etc., " Am.J.Respir.Crit.Care Med. " 155:1835-1840 (1997); Fahy etc., " Am.J.Respir.Crit.Care Med. " 155:1828-1834 (1997)).Utilize these anti-IgE antibodies to treat atopic dermatitis and then do not carry out any clinical trial as yet.Because shortage is interrelated between the seriousness of high IgE content and atopic dermatitis symptom, common people can not anticipate that these antibody will can be used for the treatment of atopic dermatitis.As for other IgE antagonisies, be to be attached to Fc ε R I and not cause that allergic pharmacology's amboceptor discharges and work by preventing or suppress IgE, they also can be ineffective to the treatment atopic dermatitis by expection.This class antagonist comprises micromolecule and other new chemistry or biological entities.
Summary of the invention
The present invention includes a kind of pharmaceutical composition that is used for the treatment of atopic dermatitis, said composition comprises the IgE antagonist that can not cause allergic pharmacology's amboceptor to discharge.This class antagonist comprises the monoclonal anti-IgE antibodies, and this antibody can be in conjunction with secretory IgE, but not can in conjunction with the IgE that is present in the Fc ε R I receptors bind on basophil, mastocyte or the langerhans' cells.These anti-IgE antibodies are preferred combination film conjunction type IgE also, and helps downward modulation thus or remove the B cell that generates IgE, the feasible content that further reduces secretory IgE.These anti-IgE antibodies preferred not in conjunction with the IgE of the Fc ε R II receptors bind of low-affinity.If antibody of the present invention with combine with the IgE of Fc ε R II receptors bind, then may cause destroying or reduce B cell or other cell types of producing other kinds immunoglobulin like protein, this will not expect.
Though judge according to conventional, depend alone and reduce or remove IgE and additional other modes will can not treated atopic dermatitis effectively, the prerequisite of the application's foundation then is: the IgE antagonist, comprise independent anti-IgE antibodies, and will prove effective healing potion.In fact, anti-IgE antibodies will prove can provide the better essence effect of expecting than those skilled in the art to atopic dermatitis patients.
If selected IgE antagonist is an anti-IgE antibodies, then can utilize following technology that it is modified, purpose is to lower its antigenicity to be more suitable for the human body administration.Described technology comprises antibody chimeric method (chimerization), humanization (transplanting) by CDR, or opposite, comprise with transgenic animal and produce human antibody or pass through the single-chain fragment that the phage display library technology is produced people's antibody.Preferred these antibody have human IgG l or IgG3 CH, because this known cytolysis that mediates ADCC and complement-mediated in class zone can be assisted thus and be removed the B cell that generates IgE.Pharmaceutical composition of the present invention is when may being the most effective by such as the inner administration of modes such as intravenous, intramuscular or subcutaneous injection the time.It also can utilize the suitable carrier that is not subjected to digest and decompose by the inner administration of oral way; Perhaps send into the alveolar of pulmonary by inhaler.In addition, the also possible topical of said composition is allowed to condition at this absorption and part and works to infected position.
Implement and use description of the invention
1. enforcement various embodiments of the present invention
Be suitable for use as the chemistry of IgE antagonist or biological entities and can utilize several different methods to select and screen, comprise using and similarly measure with the following method that is used for screening TES-C21.Basically, the first step of these methods will be the material of screening in conjunction with secretory IgE, select the molecule that can not cause allergic pharmacology's amboceptor to discharge thereafter from these materials again.Many different algoscopys well known to those skilled in the art all can be used to finish this work.
In a specific embodiments, be used for monoclonal anti-IgE antibodies of the present invention and produce by successive (immortalization), stable antibody-producting cell system.Preferred antibody-producting cell is to be hybridoma and rotaring lymphoma transfecting cell system.But, they also can be contain and can express reset through function, coding any cell line of gene of the antibody of studying (or fragment).The lymphoid cell of energy natural production assembly type immunoglobulin is preferred.
The hybridoma of the specific antibodies that production the present invention is used can prepare with the standard body hybridoma technique (" nature " 256:495,1975) of Kohler and Milstein, or with using different similar approach preparations of merging reagent.This method is summarized as follows: use people IgE that has determined to comprise the epitope of being studied that is arranged in IgE Fc zone or the B cell that generates IgE or the peptide section of people IgE (secreting type or membrane type) that animal is carried out immunity inoculation, thereby produce monoclonal anti-IgE antibodies.Peptide can chemosynthesis or is used recombinant DNA technology production, for the enhancement antigen effect, itself and carrier protein is puted together such as keyhole chirp hemocyanin.Afterwards, the animal that crosses from immunity inoculation obtains lymphoid cell (as splenocyte), and makes itself and infinite multiplication cell (for example myeloma or different myeloma) merge the generation hybrid cell.The screening technique that these hybrid cell reuse are hereinafter described in detail filters out those that can produce required anti-IgE antibodies.
When considering the antibody long term administration, just when treating atopic dermatitis with anti-IgE herein, these antibody are preferably human antibodies or are essentially human antibodies, to reduce or eliminate human anti-mice (HAMA) antibody response.The mouse antibodies part itself may trigger allergy, and perhaps the HAMA at this class part reacts the effect that may reduce treatment.
People's hybridoma of secretion human antibodies can be produced by K hler and Milstein technology.Although preferred especially human antibodies during the treatment human disease, generally speaking, it is quite difficult utilizing the stable people-people's hybridoma of this technology generation to come the long-term production human monoclonal antibody.Another kind of technology of producing human antibodies is to utilize transgenic mice.In brief, the method involves destroys endogenous Mus heavy chain and κ light chain position, makes up subsequently and contains V, D, the heavy chain of J section and κ light chain transgenic, and the C gene of human origin.Then, use human transgenic these genes to be introduced in the mice body by the pronucleus microinjection.These mices produce human antibodies through hybridization and generate bacterial strain.This technology is specified in many documents, and one of them is a United States Patent (USP) the 5th, 569, No. 825.This technology can be by GenPharm International, and Inc. (USA) authorize and obtain for Mountain View, California by company.
The another kind of method that solves the antigenicity problem is to utilize the phage display library method to produce as whole mankind's antibody fragments such as strand Fv districts.In brief, the method relates to by polymerase chain reaction (PCR) from bone marrow, blood and the human V gene of tonsil sample amplification repertoire, and then preparation contains the independent library of heavy chain and light chain (κ chain and λ chain) V gene.Then these independent segments are assembled to and are used to be illustrated in phage surface among the strand Fv, can easily filter out required fragment herein.The list of references of this technology of more detailed description comprises United States Patent (USP) the 5th, 565, No. 332 and European patent 0589877B1 number.This technology also can be authorized by the Cambridge Antibody Technology Limited of England Melbourn and be obtained.
With rodent particularly mice to produce antibody be a quite complete technology.Reduce that the other method of muroid part is to produce this antibody by the rodent system earlier in the anti-IgE antibodies, by other technology of determining they are transformed into chimeric rodent/people's antibody again or CDR moves the humanized antibody of growing.Chimeric antibody can be produced described in No. 397 as United States Patent (USP) the 4th, 816.The manufacturing of humanized antibody sees various list of references, comprises following patent: United States Patent (USP) the 5th, 693,762; 5,693,761; 5,225, No. 539 and WO89/06692 and WO92/22653 etc.
Anti-IgE antibodies of the present invention (being called TES-C21) and chimeric Mus/people's form thereof an example of (claiming TESC-2) has been described in the International Patent Application WO 92/17207.The screening scheme of TES-C21 and TESC-2 (stating as follows) can be used for screening other anti-IgE antibodies equally, is fit to chimeric or transplants humanized antibody of the present invention by CDR-to make.The hybridoma cell line of producing TES-C21 can be positioned at American type culture collection (ATCC) acquisition in Rockville city, U.S. Maryland state certainly, and registration number is 11134, and the cell line of producing TESC-2 is deposited in this with registration number BRL10706.
The humanization modification for preparing mouse antibodies TES-C21 according to the method for describing in detail in No. the 675449th, Australia patent of authorizing on May 25th, 1997.Similar operation can be used to produce other anti-IgE humanized antibodies.Production is applicable to that several transfectomas of humanization anti-IgE antibodies of the present invention can obtain from ATCC, and its registration number is respectively 11130; 11131; 11132; 11133.Wherein, a kind of have the complete clinical development potential that is used for treating atopic dermatitis with anti-IgE antibodies like the antibody class of the transfectoma production of registration number 11131 preservations.The humanized antibody that another kind is suitable for treating atopic dermatitis is E25 (rhuMAb-E25), and by Genentech, Inc. company produces.This antibody describes in detail in following document: Presta etc., " IMMUNOLOGY KEY WORDS INDEX 151:2623-2632 (1993).The production of A.TES-C21 and TESC-2 and screening
Production as described below and screening TES-C2 and TESC-2.In brief, male Balb/c mice is provided by polyclone IgE (being provided by Vertex company) the inoculation several from human serum.This IgE mixes with suitable adjuvant.After last injecting immune is former mice is put to death, take out spleen, be prepared into single-cell suspension liquid in order to merging with the myeloma cell.Splenocyte utilizes integrative mixture and the Sp2/O cell fusion of Polyethylene Glycol-1450 (Kodak), CMF-PBS and DMSO.Mix the back at cell suspending liquid and add DMEM.
The hybridoma that is produced by this fusion utilizes enzyme-linked immunosorbent assay (ELISA) at screening with the dull and stereotyped bonded people IgE of Immulon2.One of these hybridomies are promptly produced TES-C21.
TES-C21 further screens with ELISA, and selecting has specificity to people IgE, and not with those of reaction such as IgG, IgM, IgA, IgD, human serum albumin, transferrins or insulin.TES-C21 combines finely with various IgE molecules equally.In addition, TES-C21 also relies on cell line SKO-007, U266 and the SE44 of mode in conjunction with secretion IgE with dosage, shows that this antibody can be in conjunction with human film conjunction type IgE.But TES-C21 is not in conjunction with the human B cell line of carrying surperficial IgM, IgD, IgG or IgA; T cell line; Or the muroid blast cell of SE44 system; Or secrete the mouse cell line of chimeric human IgG.Also not in conjunction with the IgE on high affinity Fc ε R I receptor or the low-affinity Fc ε R II receptor, these receptors are presented on the various cell types TES-C21.In addition, TES-C21 does not also induce histamine release to the human blood basophil (its surperficial Fc ε R is stained with IgE) of prepared fresh.TES-C21 can suppress the combination of the IgE of 1 μ g to Fc ε R II fully under the concentration of 10 μ g/ml.
In order to produce TESC-2,, and be distributed to and be used on the 96 hole flat boards selecting variable region and the people γ 1 and the κ constant region cotransfection of Sp2/O cell with TES-C21 heavy chain and light chain.Screening secretion with the supernatant of the bonded human IgG of people IgE.Allow rotaring lymphoma transfecting cell in the culture medium of serum-free, adapt to growth.TESC-2 utilizes immobilization protein A post purification from the culture medium of confluent culture then.
TES-C21 and TESC-2 can be fine in conjunction with getting equally to the IgE that is combined on the microtitration plate.This can as described belowly be proved: Immulon2 is dull and stereotyped with gp120 peptide-ovalbumin conjugate bag quilt, and IgE-SE44 is attached on the immobilized antigen.The TES-C21 or the TESC-2 that add various concentration.Goat anti-mouse IgG of puting together in conjunction with situation utilization and horseradish peroxidase (HRP) (survey TES-C21 with) or the anti-human IgG Fc of HRP-goat (survey TESC-2 with) detect.
According to surveying and determination, TES-C21 has identical relative affinity with TESC-2 to the IgE that is combined on the microtitration plate.Immulon2 is dull and stereotyped with gp120 peptide-ovalbumin conjugate bag quilt, and IgE-SE44 is attached on the immobilized antigen.TES-C21 and TESC-2 add with variable concentrations respectively, and precincubation added the biotinylation TES-C21 of 0.22 μ g/ml after 1 hour.Biotinylation TES-C21 detects in conjunction with the Succ-PEG-DSPE that utilizes and horseradish peroxidase is puted together.
TES-C21 and TESC-2 also demonstrate equal combination to the cell that generates IgE.This is proved by following method: with cell in 2 * 10
6Under the state of cell/100 μ l PBS-1% lowlenthal serums under different antibodies concentration 0 ℃ of incubation 30 minutes.TES-C21 utilizes FITC-goat (Fab ') in conjunction with situation
2Anti-mice IgG measures; TESC-2 then utilizes FITC-goat (Fab ') in conjunction with situation
2Anti-human IgG is measured.Use Coulter Epics V by the quantitative assay of fluorescent flow cytometry in conjunction with situation.FITC intensity door is arranged on and obtains 10% ± 0.5% positive cell when not having initial immunoglobulin.
TES-C21 and TESC-2 the two to being combined in the not combinations of IgE on the low-affinity IgE receptor.It is that the cell of IM-9 is studied that TESC-2 identification and the probability of the compound IgE of CD23 are utilized the human lymphoblastoid of an IgG secretion.Exist on the IM-9 cell CD23 can resist by it by anti--Leu20 conclusive evidence that dyes by force-Leu20 a kind ofly has specific MAb to CD23.The IM-9 cell washs with the people IgE incubation of 5 to 10 μ g/ml, uses the anti-IgE Mab of biotin labeled TESC-2 or positive control TES-19 incubation then, and last reuse FITC-Succ-PEG-DSPE incubation is by the flow cytometry analysis.
The two all can suppress the combination of IgE to Fc ε R II chimeric TESC-2 and Mus TES-C21.Antibody under variable concentrations with 20 μ g IgE-SE44 37 ° of following precincubation one hour, add the IM-9 cell have Fc ε R II then.IgE uses biotinylation TES-19 and FITC-Succ-PEG-DSPE to detect with the situation that combines of cell, and quantitative with the fluorescent flow cytometry.
TESC-2 and IgE form immune complex in the precincubation process in these experiments in order to get rid of, it combines with cell and produces false-positive probability, confirms that with biotin labeled TESC-2 or FITC goat anti-human IgE (having TES-C21) these immune complexs are not also in conjunction with Fc ε R II.
TESC-2 and TES-C21 can not induce the human blood basophil (the Fc ε R on it is combined with IgE) of prepared fresh to discharge histamine.Because the basophil of different donors discharges different amboceptors, so antibody is being tested to the basophil preparation from the independent donor more than 50 under the multiple concentration.Do not observe TESC-2 or TES-C21 induces histamine release.
May be in conjunction with basophil but do not induce receptor to take place crosslinked and cause the problem of histamine release in order to solve TES-C21, use second antibody to carry out crosslinked.Because independent anti-human IgG can be induced histamine release, therefore in these experiments, only use murine antibody TES-C21.Crosslinked goat anti-mouse IgG has strengthened the inductive histamine release of contrast anti-IgE antibodies by inferior optimum concentration.But, even TES-C21 does not still induce histamine release under these very tolerant conditions.
Further detect TESC-2, whether can block the combination of IgE to determine it, and whether TESC-2 can be in conjunction with these receptor with the immune complex of IgE Fc ε R1 receptor.Whether suppress people IgE in conjunction with Fc ε R1 in order to measure TESC-2, the human peripheral basophil of having removed IgE by processing under low pH value is used peptide antigen is had active chimeric IgE reload or sensitization derived from SE44.The function of SE44-IgE is measured in conjunction with the inductive histamine release of compound that stops by the bonded multivalence R15K peptide-ovalbumin in IgE-SE44 variable region.IgE-SE44 has suppressed IgE after with TESC-2 precincubation and has been attached on the Fc ε R1.When elder generation was with another kind of IgE (PS) incubation before the basophil contact IgE-SE44, it was suppressed with combining also of IgE-SE44.Can suppose that TESC-2 and IgE have formed immune complex in the precincubation process and they can not cause histamine release.These experimental conditions and result are summarised in the following table 1.
Table 1:TESC-2 is to the inhibition of IgE in conjunction with high-affinity IgE receptor
| Histamine release net value (total %) | ||
| Basophil loads the condition of IgE-SE44 | Stimulate with R15K peptide-ovalbumin | Stimulate with anti-IgE |
| IgE-SE44 is without TESC-2 precincubation | ?????????37 | ????66 |
| IgE-SE44 TESC-2 precincubation | ?????????3 | ????68 |
| IgE-SE44 IgE-PS precincubation | ?????????0 | ????63 |
CDR-transplanting modification for the mentioned TES-C21 in front has also been carried out above-mentioned these researchs, and has obtained similar result.
2. use Antybody therapy atopic dermatitis of the present invention
IgE antagonist of the present invention or antibody must be safe and effective to confirm it through the human clinical trial before can selling.The explanation of giving one example, clinical trial can be begun by maximum 30 atopic dermatitis patients.Though these patients have carried out regular treatment at atopic dermatitis, as treating with antihistamine drug, corticosteroid, alleviation bath and washing liquid etc., its symptom still continues to occur.These patients are the anti-IgE antibodies of 50 to 300 milligrams of intravenous or subcutaneous injections, weekly, every other week or injection in every month once, 3 to 6 months by a definite date.Anti-IgE treatment is to the curative effect of atopic dermatitis patients will give a mark with for example SCORAD index (referring to B.Kung etc., " dermatological " 195:10-19,1997).To assess this therapy in addition to the influence of circulation IgE concentration and the relation between the clinical efficacy.
Other researchs will be tested different dosage regimens, dosing interval, and will be more anti-IgE treatment and the difference of comforting between the medicament.Also will study the effect of the anti-IgE of topical application.Pharmaceutical composition of the present invention is by behind any acceptable administration, and the expection meeting produces remarkable benefit to atopic dermatitis patients.
Above description, term, expression way and embodiment etc. only are exemplary, do not have restriction.The present invention includes the counterpart of all previous embodiments, no matter be known or unknown.Protection scope of the present invention is only limited by following claims, and should be by any statement or other any source decisions of other any parts of presents.
Claims (13)
1. pharmaceutical composition that is used for the treatment of atopic dermatitis, it comprises the IgE antagonist.
2. pharmaceutical composition that is used for the treatment of atopic dermatitis, it comprise combine with secretory IgE but not with the bonded anti-IgE antibodies of basophil.
3. pharmaceutical composition that is used for the treatment of atopic dermatitis, it comprise combine with secretory IgE and film conjunction type IgE but not with the bonded anti-IgE antibodies of basophil.
4. pharmaceutical composition that is used for the treatment of atopic dermatitis, it comprises and combines with secretory IgE and film conjunction type IgE but not with basophil with combined the bonded anti-IgE antibodies of IgE of Fc ε R II receptor.
5. as any one described pharmaceutical composition in the claim 2 to 4, wherein anti-IgE antibodies is not in conjunction with mastocyte.
6. as any one described pharmaceutical composition in the claim 2 to 4, wherein anti-IgE antibodies is a monoclonal antibody.
7. pharmaceutical composition as claimed in claim 6, wherein anti-IgE antibodies is chimeric antibody, moves through CDR and grow humanized antibody, or human antibodies.
8. pharmaceutical composition as claimed in claim 6, wherein the effect target of anti-IgE antibodies is people IgE.
9. pharmaceutical composition as claimed in claim 8, wherein anti-IgE antibodies has human IgG1 or IgG3 CH.
10. as any one described pharmaceutical composition in the claim 2 to 9, it further comprises makes said composition be suitable for excipient and the solvent that uses in the body.
11. pharmaceutical composition as claimed in claim 10, wherein excipient and solvent make said composition be suitable for subcutaneous or intravenous injection.
12. a pharmaceutical composition that is used for the treatment of atopic dermatitis, it comprises anti-IgE antibodies, and this antibody has and the identical performance of antibody that generates with the cell line of registration number BRL10706 preservation in American type culture collection.
13. a pharmaceutical composition that is used for the treatment of atopic dermatitis, it comprises anti-IgE antibodies, and this antibody has and the identical structure of antibody that generates with the cell line of registration number 11131 preservations in American type culture collection.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7303398P | 1998-01-29 | 1998-01-29 | |
| US1526998A | 1998-01-29 | 1998-01-29 | |
| US09/015,269 | 1998-01-29 | ||
| US60/073,033 | 1998-01-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1289253A true CN1289253A (en) | 2001-03-28 |
Family
ID=26687160
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99802505A Pending CN1289253A (en) | 1998-01-29 | 1999-01-06 | Treating atopic dermatitis with lgE antagonists |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1056471A4 (en) |
| JP (1) | JP2002501905A (en) |
| CN (1) | CN1289253A (en) |
| AU (1) | AU2103699A (en) |
| WO (1) | WO1999038531A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102993306A (en) * | 2003-02-01 | 2013-03-27 | 唐纳士公司 | High affinity, anti-human IgE antibodies |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010519194A (en) * | 2007-02-15 | 2010-06-03 | アストラゼネカ・アクチエボラーグ | Binding elements for IgE molecules |
| GB201610198D0 (en) * | 2016-06-10 | 2016-07-27 | Ucb Biopharma Sprl | Anti-ige antibodies |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5449760A (en) * | 1987-12-31 | 1995-09-12 | Tanox Biosystems, Inc. | Monoclonal antibodies that bind to soluble IGE but do not bind IGE on IGE expressing B lymphocytes or basophils |
| WO1992017207A1 (en) * | 1991-03-26 | 1992-10-15 | Tanox Biosystems, Inc. | MONOCLONAL ANTIBODIES WHICH BIND TO SECRETED AND MEMBRANE-BOUND IgE, BUT NOT TO IgE ON BASOPHILS |
| KR950702628A (en) * | 1992-08-01 | 1995-07-29 | 치세이 라 | Antiallergic Agents |
| JPH07118168A (en) * | 1993-10-19 | 1995-05-09 | Tomoyasu Ra | Ige production suppressing agent |
| DE69333484T2 (en) * | 1992-09-24 | 2005-03-24 | Novartis Ag | Reshaped monoclonal antibodies against an immunoglobulin isotype |
| MY120425A (en) * | 1996-07-26 | 2005-10-31 | Novartis Ag | Fusion polypeptides |
-
1999
- 1999-01-06 WO PCT/US1999/000135 patent/WO1999038531A1/en not_active Application Discontinuation
- 1999-01-06 AU AU21036/99A patent/AU2103699A/en not_active Abandoned
- 1999-01-06 CN CN99802505A patent/CN1289253A/en active Pending
- 1999-01-06 EP EP99901309A patent/EP1056471A4/en not_active Withdrawn
- 1999-01-06 JP JP2000529263A patent/JP2002501905A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102993306A (en) * | 2003-02-01 | 2013-03-27 | 唐纳士公司 | High affinity, anti-human IgE antibodies |
| CN102993306B (en) * | 2003-02-01 | 2015-01-28 | 唐纳士公司 | High affinity, anti-human IgE antibodies |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999038531A1 (en) | 1999-08-05 |
| EP1056471A4 (en) | 2001-05-30 |
| JP2002501905A (en) | 2002-01-22 |
| EP1056471A1 (en) | 2000-12-06 |
| AU2103699A (en) | 1999-08-16 |
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