Ex parte CAMPBELL

Board of Patent Appeals and Interferences

Sep 25, 1998

07939556 (B.P.A.I. Sep. 25, 1998)

Application for patent filed September 1, 1992. According to the appellant, this1
application is a continuation of Application 07/058,344, filed June 5, 1987, now
abandoned; which is a division of Application 06/596,447, filed April 3, 1984, now U.S.
Patent 4,693,893, issued September 15, 1987; which is a continuation of Application
06/565,648, filed December 27, 1983, now abandoned.
1
THIS OPINION WAS NOT WRITTEN FOR PUBLICATION
The opinion in support of the decision being entered today (1) was not written for
publication in a law journal and (2) is not binding precedent of the Board.
Paper No. 40
UNITED STATES PATENT AND TRADEMARK OFFICE
_____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
_____________
Ex parte DAVID A. CAMPBELL

_____________
Appeal No. 94-3187
Application 07/939,5561
______________
ON BRIEF
_______________
Before WILLIAM F. SMITH, SCHAFER and ELLIS, Administrative Patent Judges.
WILLIAM F. SMITH, Administrative Patent Judge.
Appeal No. 94-3187
Application 07/939,556
2
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the final rejection of claims 1, 4
through 9 and 12 through 15, all the claims in the application.
Claims 1, 6, 12 and 15 are illustrative of the subject matter on appeal and read as
follows:
1. A genetically reassorted virus grown in cell culture in sufficient quantities to be
useful for vaccine preparation without need of further multiplication, said virus being
derived from an equine influenza virus and the human influenza virus A/Puerto Rico/8/34
which reassorted virus comprises RNA derived from the equine influenza virus coding for
at least one neuraminidase or haemagglutinin surface antigen and the RNA segment
derived from A/Puerto Rico/8/34 which codes for matrix protein.
6. A process for the preparation of a genetically reassorted virus comprising the
steps of:
(a) allowing (i) equine influenza virus and (ii) the human influenza virus strain
A/Puerto Rico/8/34 or a virus comprising the RNA 7 segment thereof to grow under
conditions in which genetic reassortment can take place,
(b) selecting for genetically reassorted viruses having surface antigens from only the
equine virus and having the RNA 7 segment derived from the A/Puerto Rico/8/34 virus,
and
(c) growing those said reassortants from step (b) in cell culture.
12. A vaccine for equine influenza comprising an effective vaccination amount of
attenuated genetically reassorted virus grown in cell culture and derrived [sic] from either or
both of Eq1 and Eq2 equine influenza virus and the human influenza virus A/Puerto
Rico/8/34, which reassorted virus comprises RNA derived from the equine influenza virus
coding for at least one neuramidase or haemagglutinin surface antigen and an RNA
segment derived from A/Puerto Rico/8/34, which codes for matrix protein in association
Appeal No. 94-3187
Application 07/939,556
3
with a veterinary acceptable carrier which can contain an adjuvant suitable for use as
vehicle to introduce the attenuated virus into the animal.
15. A method of vaccinating a horse against influenza by administration to the
horse of an effective amount of (a) one, or (b) a primary followed by a secondary dosage
with an interval of about 3 to about 7 weeks between doses of a genetically reassorted
virus derived from equine influenza virus, attenuated and formulated with a veternary [sic]
acceptable carrier which can contain an adjuvant as a vaccine according to claim 12.

The references relied upon by the examiner are:
Coggins et al. (Coggins) 4,683,137 July 28, 1987
Bosch et al. (Bosch), "RNA and Protein Synthesis in a Permissive and an Abortive
Influenza Virus Infection," in “Negative Strand Viruses and the Host Cell,” eds. Mahy et al.,
Academic Press, pp. 465-473 (1978).
Baez et al. (Baez), "Gene Composition of High-Yielding Influenza Vaccine Strains
Obtained by Recombination," The Journal of Infectious Diseases, vol. 141, pp. 362-365
(1980).
Brundage-Anguish et al. (Brundage-Anguish), "Live Temperature-Sensitive Equine
Influenza Virus Vaccine: Generation of the Virus and Efficacy in Hamsters," Am. J. Vet.
Res., vol. 43, pp. 869-874 (1982).
Claims 1, 4 through 9 and 12 through 15 stand rejected under 35 U.S.C. § 103 as
unpatentable over either Coggins or Brundage-Anguish taken in view of Baez and Bosch.
We reverse.
BACKGROUND
The present invention is directed to genetically reassorted viruses derived from an
equine influenza virus and the human influenza virus A/Puerto Rico/8/34 (PR8). The
Appeal No. 94-3187
Application 07/939,556
4
reassorted virus contains RNA derived from the equine influenza virus coding for at least
one neuraminidase or hemagglutinin surface antigen and the RNA segment from PR8
which codes for matrix protein. As set forth in the abstract of this application, appellant
found that these reassortments will grow in cell culture even though the equine influenza
virus used as a parent will not.
The ability of the present reassorted virus to grow in cell culture is discussed at
page 3, lines 4-9, of the specification as follows:
It has now surprisingly been found that if an equine influenza
virus is genetically reassorted to produce a virus containing
certain RNA derived from A/Puerto Rico/8/34, the genetically
reassorted virus is able to grow in cell culture. There is no
clear correlation between having a high yield in eggs and the
ability to grow in cell culture, and there is no teaching in the
prior art to suggest that a virus which grows well in eggs is
likely to grow in cell culture.

and at page 4, lines 3-14, of the specification as follows:
The involvement of matrix protein in general in virus growth
in cell culture was suggested by Bosch et al, ( in Negative
Strand Viruses and the Host Cell (1978), Academic Press,
edited by B. W. J. Mahy and others, page 465). However, this
paper relates to the growth of fowl plague virus (FPV) and no
mention is made of equine influenza virus. In view of the well
known difficulty in making predictions about the behaviour of
one type of influenza virus based on observations of another,
this distinction is by no means trivial. See, for example
Scholtissek et al, Virology (1977) 81 74-80, which illustrates
the proposition that apparently small changes between
influenza viruses have profound effects. This is amplified by
Appeal No. 94-3187
Application 07/939,556
5
Sweet and Smith (Microb. Revs. (1980) 44 (22), 303-30).
Furthermore, there has been no suggestion that the segment in
A/PR/8/34 coding for matrix protein is effective in conferring
the ability to grow in cell culture.
As explained at page 3, lines 27-30, of the specification, it is important to understand that:
Whereas it has been established by the applicants that the
RNA segment which codes for matrix protein enables growth
in cell culture to take place, it is not clear as to whether the
matrix protein itself confers this ability: it may be some other
gene product coded by the same RNA segment.
DISCUSSION
Assuming, without deciding, that the combined disclosures of Coggins, Brundage-
Anguish and Baez would have suggested to one of ordinary skill in the art to form a
genetically reassorted virus derived from an equine influenza virus and PR8 which
comprises RNA derived from the equine influenza virus coding for at least one
neuraminidase or hemagglutinin surface antigen and the RNA segment derived from PR8
which codes for matrix protein, that would not end the inquiry. Rather, a second
determination would have to be made as to whether the applied prior art would have led
one skilled in the art to reasonably expect that such a reassorted virus would grow in cell
culture. For this aspect of the claimed invention, the examiner relies upon Bosch.
Bosch acknowledges in the abstract that many influenza virus infections of cells in
culture do not result in the production of infectious virus. Bosch used Fowl Plague Virus
Appeal No. 94-3187
Application 07/939,556
6
(FPV) to infect L cells and chick embryo fibroblasts. FPV infection of L cells resulted in
low viral virus yields while the FPV infections of chick embryo fibroblasts resulted in
relatively high virus yields. In order to define the factors responsible for these disparate
results, Bosch compared the virus-specific RNA and protein synthesis of the two systems.
The examiner relies upon Bosch’s observation, set forth in the last full paragraph of page
467, that of the proteins analyzed in the chick embryo fibroblast and L cell cultures, the
synthesis of matrix protein was reduced in the L cell culture. The examiner has inferred
that the relatively higher production of matrix protein in the chick embryo fibroblast culture
was responsible for the relatively higher virus yields obtained in that system. From this
inference, the examiner concluded that one of ordinary skill in the art would have
understood at the time of the present invention, from a consideration of all four of the
applied references together, that a reassorted virus containing the RNA encoding matrix
protein of PR8 would have expectedly been able to grow in high yields in cell culture. We
disagree.
In our view, the narrow disclosure of Bosch does not support the sweeping
conclusion reached by the examiner. Bosch initially indicates that many influenza virus
infections of cells in culture do not result in the production of infectious virus. That teaching
in and of itself provides evidence that the area in which appellant is working has a high
degree of unpredictability. While infection of chick embryo fibroblasts resulted in relatively
Appeal No. 94-3187
Application 07/939,556
7
high virus yields, Bosch, considered in its entirety, indicates to us that the results to be
obtained from an influenza virus infection of cells in culture at the time of the present
invention was unpredictable. This determination is consistent with appellant’s
characterization of the prior art at page 4, lines 3-14, of the specification referred to above.
When we consider the entire record, it is our view that one of ordinary skill in the art
at the time of the present invention would not have reasonably expected that a reassorted
virus derived from equine influenza virus and PR8 and containing the RNA’s required by
the claims on appeal would be capable of growing in cell culture.
The decision of the examiner is reversed.
REVERSED
)
WILLIAM F. SMITH )
Appeal No. 94-3187
Application 07/939,556
8
Administrative Patent Judge )
)
)
) BOARD OF PATENT
RICHARD E. SCHAFER )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
JOAN ELLIS )
Administrative Patent Judge )
sd
Donald Brown
130 Water Street
Boston, MA 02109