This is a patent called "Product for inhibition of infection of mammalian
cells by respiratory syncytial virus." The assignee to this patent is
Abbott. The patent is for a liquid enteral nutritional product, or a liquid
enteral nutritional infant formula, or nasal spray. Whether Abbott has used
this patent in its production of infant formula is something I don't know.
But why go to all the expense of patenting? Just thought it might of
interest to some Lactnetters. Sorry for the length...although this is only a
partial copy of the whole patent # 5506209 at
http://www.uspto.gov/patft/index.html
Valerie W. McClain, IBCLC....human milk is pretty darn amazing...so amazing
that the infant formula industry is willing to put it into formula..
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"The present invention relates generally to inhibiting the infection of
mammalian cells by Respiratory Syncytial Virus and more specifically to the
use of native or recombinant human .beta.-casein and hydrolysates thereof for
inhibiting the infection of mammalian cells by Respiratory Syncytial Virus.
Respiratory Syncytial Virus (RSV) is the single most frequent cause of acute
respiratory tract infection in infants and children. Infants less than six
months of age are most frequently and seriously affected. In most
immunologically normal subjects, infection with RSV is limited to the
respiratory mucosa, and is associated with the development of bronchiolitis,
pneumonia and reactive airway disease. RSV infection in immunocompromised
subjects has until recently been associated with increased mortality in
infants and increased morbidity in other age groups. It has recently been
reported in PEDIATRIC NOTES, Vol. 18, No. 9, Jan. 27, 1994, that periods of
high incidence of acute respiratory disease and numbers of deaths in elderly
people were followed within 2-3 weeks by reports of high numbers of RSV or
influenza virus isolates. The analyses indicate that RSV is as important as
influenza viruses in causing morbidity and deaths among the elderly.
It has been reported that some respiratory disease may be prevented by breast
feeding, and that "bronchiolitis of infants due to respiratory syncytial
virus is less frequent in breast fed than in artificially fed infants". While
human breast milk can contain antibodies to RSV, it has been found that milk
also has antiviral activity that is not due to antibodies. It has been
theorized that this effect "may be produced by certain polysaccharides which
are found on a number of different molecular constituents of milk." Tyrrell,
"BREAST FEEDING AND VIRUS INFECTIONS", THE IMMUNOLOGY OF INFANT FEEDING,
edited by A. W. Wilkinson, Plenum Press, New York, N.Y. pages 55-62 (1981).
Okamato, et al., "Antiviral Factors in Human Milk: Implications in
Respiratory Syncytial Virus Infection", ACTA PAEDIATRICA SCANDANAVICA
SUPPLEMENT, 351:137-143 (1989) disclose that while the mechanisms of
protective immunity to RSV had not been clearly defined, immunity acquired
transplacentally or via breast feeding has been suggested to reduce the risk
of lower respiratory tract disease. However, this publication focuses upon
the role of antibodies transmitted in breast milk or the possible role of
breast milk in modulating an infant's RSV immune response.
Laegreid et al., "Neutralizing Activity in Human Milk Fractions against
Respiratory Syncytial Virus", ACTA PAEDIATRICA SCANDANAVICA, 75:696-701
(1986) reports a study which confirms that human milk may contain
RSV-neutralizing activity of a non-immunoglobulin nature as well as
RSV-specific antibody. However, the identity and mechanism of the
non-immunoglobulin anti-RSV component of human milk is not identified. It is
important though to note that Laegreid et al. disclose that RSV-neutralizing
components from breast milk may reach an infant's respiratory tract directly
as a result of regurgitation and inhalation of milk during and after feeding.
The mucosa of the respiratory tract may gain direct protection in this way.
WO 91/06308 filed by Andersson et al. for "ANTIBACTERIAL COMPOSITION", and a
published article by the same authors (Aniansson et al., "Anti-adhesive
activity of human casein against Streptococcus pneumonia and Haemophilus
influenzae", MICROBIAL PATHOGENESIS, 8:315-323 (1990) disclose the use of a
milk fraction having a molecular weight of at least 5,000 daltons for
"therapeutic prophylactic, and/or diagnostic use in infections caused by S.
pneumonae and/or H. influenzae", but it is suggested in these publications
that the beneficial effect is provided by kappa-casein. However, the present
invention relates to the use of native or recombinant human .beta.-casein and
hydrolysates of both to inhibit RSV infections.
WO93/04172 relates to a DNA sequence encoding human .beta.-casein, but does
not disclose the ,capacity of either native or recombinant human
.beta.-casein to inhibit the attachment of RSV to human cells.
WO91/08675 discloses an infant formula which contains recombinant forms of
both human alpha-lactalbumin and human .beta.-casein. However, this
publication discloses only that these human milk proteins will "give a
simulated human mother's milk formula that does not exhibit the allergenic
properties associated with formulas based on cow or other foreign protein."
(page 3, lines 20-22). The use of human .beta.-casein to inhibit the
attachment of RSV to human cells is not taught or suggested in said
publication.
The two assays (a HEp-2 cell assay and a LLC-MK2 cell assay) which were used
for determining the bioactivity of .beta.-casein are described below. These
assays have not been published heretofore, although the HEp-2 cell assay was
based upon established methodology.
MATERIALS USED IN BOTH ASSAYS
Native Human .beta.-Casein
.beta.-casein isolated from human milk was purchased from Symbicom AB, P. O.
Box 1451 S-901 24 Umea Sweden.
Recombinant Human .beta.-Casein
Applicants obtained .beta.-casein cDNA and the expression system from
Symbicom AB, P. O. Box 1451, S-901 24 Umea, Sweden. The human .beta.-casein
cDNA used had been previously cloned and sequenced by Lonnerdal et al.,
Cloning and sequencing of a cDNA encoding human milk .beta.-casein. (SEQ.ID
NO: 1:) Federation of European Biochemical Societies Letters 269, 153-156
(1990). The recombinant human .beta.-casein was obtained from E. coli and
purified according to the method of Hansson et al., Expression of Human Milk
.beta.-Casein in Escherichia coli: Comparison of Recombinant Protein with
Native Isoforms. Protein Expression and Purification 4, 373-381 (1993). To
express human .beta.-casein in E. coli, .beta.-casein cDNA was cloned under
control of a T7 promoter in two different expression vectors. One vector,
pS26, was designed for intracellular expression. The other vector, pS28, has
a signal sequence for extracellular expression. The procedure followed was
substantially that described by Hansson et al. "
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