# US 5,707,627 A · Methods and compositions for the direct concentrated delivery of passive immunity

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- Number: US 5,707,627 A
- Document ID: US5707627A
- Status: Granted
- Kind: A
- Application number: 08/609,912
- Filed: 1996-02-29
- Granted: 1998-01-13
- Earliest claimed: 1993-01-12
- Inventors: Anthony George Gristina; Quentin Newell Myrvik
- Web page: https://patentgrep.com/patent/US5707627A

## CPC

- A61K 39/44: Antibodies bound to carriers
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 17/00: Drugs for dermatological disorders
- A61P 27/16: Otologicals
- C07K 16/12: against material from bacteria
- C07K 16/1214: Pseudomonadaceae (F)
- C07K 16/1271: Micrococcaceae (F); Staphylococcaceae (F), e.g. Staphylococcus (G)
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Compositions containing a high concentration of the full repertoire of immunoglobulins, including IgA, IgM and IgG, are used to combat infections from microorganisms and viruses at a wound, surgical, or burn site, or normal tissue at times of risk of infection. The compositions can contain elevated antibody titers for several specific pathogens including S. aureus, CNS, Enterococci, S. epidermidis, P. aeruginosa, E. coli, and Enterobacter spp., etc. The compositions are applied directly to a wound or burn site as an ointment, creme, fluid, spray, or the like, prior to viral or bacterial attachment or biofilm formation such that adhesion of the pathogens is inhibited and the pathogens closest to the wound or burn site will be pre-opsonized for phagocytic killing prior to toxin release. The immunoglobulins in the composition can be immobilized on a biocompatible material such as collagen, fibrin, hyaluronan, biodegradable polymers, and fragments thereof, which will be placed in-situ at the wound, surgical or burn site. In addition, the immunoglobulins in the composition may be coated on the body contacting surface of an implantable device such as a catheter, contact lens or total joint. The inventive compositions have particular application in preventing infections.

## Claims

### Claim 1

An antimicrobial composition for preventing infections in human and animal hosts that are derived from wounds, burns, or biomaterials, comprising:
a pharmaceutically acceptable carrier selected from the group consisting of gels, ointments, cremes, lavage fluids, and matrix materials for application to either a tissue surface at a surgical or trauma site or a surface of a biomaterial to be inserted at a biomaterial implant site; and
a mixture of antibodies disposed in said carrier, said mixture of antibodies comprising 0.1-20% by weight of said antimicrobial composition.

### Claim 2 (depends on 1)

The antimicrobial composition of claim 1 wherein said carrier is selected from the group consisting of gels, ointments and cremes.

### Claim 3 (depends on 1)

The antimicrobial composition of claim 1 wherein said carrier is a lavage fluid.

### Claim 4 (depends on 1)

The antimicrobial composition of claim 1 wherein said carrier is a matrix material selected from the group consisting of fibrin, collagen, gelatin, hyaluronan, and polysacharide.

### Claim 5 (depends on 1)

The antimicrobial composition of claim 1 wherein said mixture of antibodies comprises IgG.

### Claim 6 (depends on 5)

The antimicrobial composition of claim 5 wherein said mixture of antibodies further comprises monoclonal antibodies.

### Claim 7 (depends on 1)

The antimicrobial composition of claim 1 wherein said mixture of antibodies comprises IgG, IgM, and IgA.

### Claim 8 (depends on 7)

The antimicrobial composition of claim 7 wherein said mixture of antibodies further comprises monoclonal antibodies.

### Claim 9 (depends on 1)

The antimicrobial composition of claim 1 wherein said mixture of antibodies comprises monoclonal antibodies.

### Claim 10 (depends on 1)

The antimicrobial composition of claim 1 wherein said mixture of antibodies comprises antibodies for least two microorganisms selected from the group consisting of S. aureus, S. epidermidis, Coagulase Negative Staph., Streptococcus (Groups. A, B, and D), P. aeruginosa, E. coli, Enterobacter spp., K. pnumoniae, S. pneumoniae, S. mutans, H. influenzae, Proteus spp., S. pyogenes, M. pneumoniae, respiratory syncytial virus, influenza virus (A, B, and C), and rhinovirus.

### Claim 11

An antimicrobial composition for preventing infections in human and animal hosts that are derived from wounds, burns, or biomaterials, comprising:
a pharmaceutically acceptable carrier selected from the group consisting of gels, ointments, cremes, lavage fluids, and matrix materials for application to either a tissue surface at a surgical or trauma site or a surface of a biomaterial to be inserted at a biomaterial implant site; and
IgG distributed in said carrier at a concentration ranging from 500-20,000 mg/dl.

### Claim 12 (depends on 11)

The antimicrobial composition of claim 11 wherein said carrier is selected from the group consisting of gels, ointments and cremes.

### Claim 13 (depends on 11)

The antimicrobial composition of claim 11 wherein said carrier is a lavage fluid.

### Claim 14 (depends on 11)

The antimicrobial composition of claim 11 wherein said carrier is a matrix material selected from the group consisting of fibrin, collagen, gelatin, hyaluronan, and polysacharide.

### Claim 15 (depends on 11)

The antimicrobial composition of claim 11 further comprising monoclonal antibodies distributed in said carrier.

### Claim 16 (depends on 11)

The antimicrobial composition of claim 11 further comprising IgM and IgA distributed in said carrier.

### Claim 17 (depends on 16)

The antimicrobial composition of claim 16 further comprising monoclonal antibodies distributed in said carrier.

### Claim 18 (depends on 11)

The antimicrobial composition of claim 11 wherein said IgG comprises antibodies for at least two microorganisms selected from the group consisting of S. aureus, S. epidermidis, Coagulase Negative Staph., Streptococcus (Groups A, B, and D), P. aeruginosa, E. coli, Enterobacter spp., K. pnumoniae, S. pneumoniae, S. mutans, H. influenzae, Proteus spp., S. pyogenes, M. pneumoniae, respiratory syncytial virus, influenza virus (A, B, and C), and rhinovirus.

### Claim 19

An antimicrobial composition for preventing infections in human and animal hosts that are derived from wounds, burns, or biomaterials, comprising:
a pharmaceutically acceptable carrier selected from the group consisting of gels, ointments, cremes, lavage fluids, and matrix materials for application to either a tissue surface at a surgical or trauma site or a surface of a biomaterial to be inserted at a biomaterial implant site; and
a mixture of monoclonal antibodies disposed in said carrier which are specific for at least two microorganisms selected from the group consisting of S. aureus, S. epidermidis, Coagulase Negative Staph., Streptococcus (Groups A, B, and D), P. aeruginosa, E. coli, Enterobacter spp., K. pnumoniae, S. pneumoniae, S. mutans, H. influenzae, Proteus spp., S. pyogenes, M. pneumoniae, respiratory syncytial virus, influenza virus (A, B, and C), and rhinovirus, said mixture of monoclonal antibodies being present at a concentration ranging from 0.01 .mu.g/ml to 5 .mu.g/ml.

### Claim 20

A method for preventing infections in human and animal hosts that are derived from wounds, burns, and biomaterials, comprising the steps of:
preparing a surgical or trauma site of a wound, burn or biomaterial implant site in a human or animal host where damaged tissue exists, wherein said preparing is selected from the the group consisting of cleaning, decontaminating, debriding and surgery;
directly applying an amount of an antimicrobial composition containing in combination a pharmaceutically acceptable carrier selected from the group consisting of gels, ointments, cremes, lavage fluids, and matrix materials, and a mixture of antibodies disposed in said carrier wherein said mixture of antibodies comprising 0.1-20% by weight of said antimicrobial composition and wherein said mixture of antibodies is selected from the group consisting of IgG, IgG in combination with IgM and IgA, IgG in combination with monoclonal antibodies, IgG in combination with IgM and IgA and monoclonal antibodies, and monoclonal antibodies, on either tissue surfaces at said surgical or truama site or on a biomaterial to be applied at said biomaterial implant site to produce an immunocompetent inflammatory zone sufficient to prevent adhesion of microorganisms to said tissue surfaces or said biomaterials or a biofilm formation and to pre-opsonize said microorganisms for rapid intracellular killing by host defense mechanisms, said step of directly applying being performed by a process selected from the group consisting of applying said antimicrobial composition to said tissue surfaces or said biomaterial implant site at a time of surgery or trauma or within a period of six hours after said surgery or trauma, or using a biomaterial pre-coated with said antimicrobial composition; and
preventing or reducing infections in said human or animal host at said surgical or trauma site with said antimicrobial composition or biomaterial pre-coated with said antimicrobial composition.

### Claim 21

A method for preventing infections in human and animal hosts that are derived from wounds, burns, and biomaterials, comprising the steps of:
preparing a surgical or trauma site of a wound, burn or biomaterial implant site in a human or animal host where damaged tissue exists, wherein said preparing is selected from the the group consisting of cleaning, decontaminating, debriding and surgery;
directly applying an amount of an immunoglobulin composition containing in combination a pharmaceutically acceptable carrier selected from the group consisting of gels, ointments, cremes, lavage fluids, and matrix materials, and IgG distributed in said carrier at a concentration ranging from 500-20,000 mg/dl on either tissue surfaces at said surgical or truama site or on a biomaterial to be applied at said biomaterial implant site to produce an immunocompetent inflammatory zone sufficient to prevent adhesion of microorganisms to said tissue surfaces or said biomaterials or a biofilm formation and to pre-opsonize said microorganisms for rapid intracellular killing by host defense mechanisms, said step of directly applying being performed by a process selected from the group consisting of applying said antimicrobial composition to said tissue surfaces or said biomaterial implant site at a time of surgery or trauma or within a period of six hours after said surgery or trauma, or using a biomaterial pre-coated with said antimicrobial composition; and
preventing or reducing infections in said human or animal host at said surgical or trauma site with said antimicrobial composition or biomaterial pre-coated with said antimicrobial composition.
