US4059571A
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Novel immunoglobulin derivatives and process for the preparation thereof
Assignee: Teijin Ltd
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Filing: 1975-03-04
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Granted: 1977-11-22
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Expires: 1995-03-04
Abstract
Abstract Novel immunoglobulin derivatives which are characterized in that in which the interchain disulfide bonds of immunoglobulin are predominantly cleaved, on the average 3 to 5 of the interchain disulfide bonds or the inter- and intra-chain disulfide bonds being cleaved, and so produced sulfur atoms (S-) are S-sulfonated (--S-SO 3 ). The above immunoglobulin derivatives are prepared by reacting native immunoglobulin with A. a compound capable of forming tetrathionate ion, and B. a compound capable of forming in water, sulfite ion whereby cleaving on the average 3 to 5 inter-chain disulfide bonds, or inter- and intra-chain disulfide bonds, of the native immunoglobulin, and S-sulfonating (S-SO 3 ) the so formed sulfur atoms. This invention also provides a water-soluble composition for injection containing said immunoglobulin derivative having the titre of anti-diphtheria of at least 1.0 I.U./ml at its concentration of 10.0% by weight, and a pharmaceutically-acceptable solubilizing agent for said immunoglobulin derivative.
Inventors
- 👤 Katsuhiko Tomibe
- 👤 Yasuhiko Masuho
- 👤 Kimihiko Matsuzawa
- 👤 Sachio Ishimoto
- 👤 Kazuo Satake
- 👤 Tsuneo Watanabe
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 12:15
CPC Classifications
C; C07; C07K; C07K16/00; C07K16/06; C07K16/065
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
57 words
Novel immunoglobulin derivatives which are substantially free from oxidizing metal ions such as cupric ion comprising immunoglobulin in which the interchain disulfide bonds are predominantly cleaved, on the average 3 to 5 of the interchain disulfide bonds or the inter- and intra-chain disulfide bonds being cleaved, and so produced sulfur atoms (S--) are S-sulfonated (-S-SO 3 ).
Claim 2
Dependent Claim
57 words
Novel immunoglobulin derivatives which are substantially free from oxidizing metal ions such as cupric ion comprising immunoglobulin in which the interchain disulfide bonds are predominantly cleaved, on the average 3 to 5 of the interchain disulfide bonds or the inter- and intra-chain disulfide bonds being cleaved, and so produced sulfur atoms (S--) are S-sulfonated (-S-SO 3 ).
Claim 3
Dependent Claim
33 words
The novel immunoglobulin derivatives of claim 1, in which on the average approximately 3 - 4.5 interchain disulfide bonds of immunoglobulin are substantially selectively cleaved, and the so produced sulfur atoms are S-sulfonated.
Claim 4
Dependent Claim
31 words
The novel immunoglobulin derivative according to claim 1, in which on the average approximately 4.5 interchain disulfide bonds of immunoglobulin are substantially selectively cleaved, and so produced sulfur atoms are S-sulfonated.
Claim 5
Dependent Claim
66 words
Immunoglobulin which is characterized in that 1. on the average 3 to 5 interchain disulfide bonds, or inter- and intra-chain disulfide bonds, of immunoglobulin are cleaved and so formed sulfur atoms (S-) are S-sulfonated (-S-SO 3 ), 2. it has the titre of anti-diphtheria of 1.0 international unit (I.U.)/ml. at its concentration of 10.0% by weight, and 3. it is substantially free from oxidizing metal ions.
Claim 6
Dependent Claim
66 words
Immunoglobulin which is characterized in that 1. on the average 3 to 5 interchain disulfide bonds, or inter- and intra-chain disulfide bonds, of immunoglobulin are cleaved and so formed sulfur atoms (S-) are S-sulfonated (-S-SO 3 ), 2. it has the titre of anti-diphtheria of 1.0 international unit (I.U.)/ml. at its concentration of 10.0% by weight, and 3. it is substantially free from oxidizing metal ions.
Claim 7
Dependent Claim
75 words
A water-soluble composition which comprises an immunoglobulin derivative which is substantially free from oxidizing metal ions in which on the average 3 to 5 interchain disulfide bonds, or inter- or intra-chain disulfide bonds, of native immunoglobulin are cleaved, and so formed sulfur atoms are S-sulfonated (S-SO 3 ), and which exhibits the anti-diphtheria titre of at least 1.0 I.U./ml at the concentration of 10.0% by weight, and a harmless solubilizing agent of said immunoglobulin derivative.
Claim 8
Dependent Claim
75 words
A water-soluble composition which comprises an immunoglobulin derivative which is substantially free from oxidizing metal ions in which on the average 3 to 5 interchain disulfide bonds, or inter- or intra-chain disulfide bonds, of native immunoglobulin are cleaved, and so formed sulfur atoms are S-sulfonated (S-SO 3 ), and which exhibits the anti-diphtheria titre of at least 1.0 I.U./ml at the concentration of 10.0% by weight, and a harmless solubilizing agent of said immunoglobulin derivative.
Claim 9
Dependent Claim
21 words
Aqueous injectable compositions which comprise an immunoglobulin derivative of claim 4, the harmless solubilizing agent of the immunoglobulin derivatives, and water.
Claim 10
Dependent Claim
73 words
A process for the preparation of immunoglobulin derivatives which comprises reacting native immunoglobulin with A. a compound capable of forming tetrathionate ion, and B. a compound capable of forming sulfite ion in water, in the substantial absence of oxidizing metal ion to thereby cleave on the average 3 to 5 interchain disulfide bonds, or inter- and intra-chain disulfide bonds, of the native immunoglobulin, and S-sulfonating (S-SO 3 ) the so formed sulfur atoms.
Claim 11
Dependent Claim
73 words
A process for the preparation of immunoglobulin derivatives which comprises reacting native immunoglobulin with A. a compound capable of forming tetrathionate ion, and B. a compound capable of forming sulfite ion in water, in the substantial absence of oxidizing metal ion to thereby cleave on the average 3 to 5 interchain disulfide bonds, or inter- and intra-chain disulfide bonds, of the native immunoglobulin, and S-sulfonating (S-SO 3 ) the so formed sulfur atoms.
Claim 12
Dependent Claim
24 words
The process for making immunoglobulin derivatives according to claim 7, in which the reaction is effected at the pH ranging from 3.5 to 10.
Claim 13
Dependent Claim
27 words
The process for making immunoglobulin derivatives according to claim 8, in which the reaction is effected at the temperature within the range of 10° - 50° C.
Claim 14
Dependent Claim
32 words
The process of claim 7 in which compound (A) is tetrathionic acid, sodium tetrathionate, potassium tetrathionate, or ammonium tetrathionate, and compound (B) is sulfurous acid, sodium sulfite, potassium sulfite or sodium bisulfite.
Claim 15
Dependent Claim
27 words
The process of claim 7 in which, on the average, 4.5 interchain disulfide bonds of immunoglobulin are selectively cleaved, and the so produced sulfur atoms are S-sulfonated.
Claim 16
Dependent Claim
32 words
The process of claim 11 wherein the reaction temperature is within the range of 15°- 48° C. and the pH during the reaction is maintained within the range of 6 to 9.
Claim 17
Dependent Claim
42 words
The process of claim 7 wherein the compound (A) and the compound (B) are each present in an amount of from 2 to 100 molar times the interchain, or inter- and intra-chain disulfide bonds of the starting native immunoglobulin to be cleaved.
References Cited (Backward Citations)
US3597409A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-11-21 | 1981-05-23 | 1981-11-22 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-11-21 | 1985-05-23 | 1985-11-22 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-11-21 | 1989-05-23 | 1989-11-22 | $7700.00 | Window Closed / Lapsed |