DeBoer v. Gordon

The opinion in support of the decision being
entered today is not binding precedent of the Board.
Paper 18
Filed by: Trial Section Motions Panel
Box Interference Filed
February 3, 2003
UNITED STATES PATENT AND TRADEMARK OFFICE
_______________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
_______________
HERMAN A. DEBOER, REIN STRIJKER,
HERBERT L. HEYNEKER, GERARD PLATENBURG, SANG HE LEE,
FRANK PIEPER, and PAUL J.A. KRIMPENFORT,
Junior Party
(Patent Nos. 5,741,957, 6,013,857, and 6,140,552),
v.
KATHERINE GORDON, SUZANNE GROET, LOTHAR HENNIGHAUSEN, and
HEINER WESTPHAL,
Senior Party
(Application 08/246,259).
_______________
Patent Interference 105,004
___________
Before: SCHAFER, TORCZON, and NAGUMO, Administrative Patent
Judges.
NAGUMO, Administrative Patent Judge.
JUDGMENT
(Under 37 C.F.R. § 1.640)
NO INTERFERENCE-IN-FACT
1. The parties have submitted a joint motion for judgment
that no interference-in-fact exists. (Paper No. 16, "JM".)

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The count:
2. Count 1, the sole count, is:
a transgenic bovine according to claim 7 of
Deboer 6,140,552 or a transgenic bovine
according to claim 18 of Gordon, 08/246,259.
3. DeBoer claim 7 is:
A bovine whose mammary gland cells have a
genome comprising in operable association:
a DNA sequence encoding a signal
sequence functional in bovine mammary gland
secretory cells;
a DNA sequence encoding a polypeptide of
interest; and
a regulatory sequence that promotes
expression of the DNA sequence encoding the
polypeptide in the mammary gland;
wherein the bovine or a female
descendant of the bovine is disposed to
express the transgene in mammary secretory
cells such that the polypeptide of interest
is detectable in milk produced by the bovine
or a female descendant of the bovine;
wherein the polypeptide is a
heterologous polypeptide.
4. Gordon claim 18 is:
A non-human mammal whose genome comprises a
DNA construct comprising a whey acidic
protein promoter operably linked to a DNA
sequence encoding a heterologous protein,
wherein said construct further comprises a
DNA sequence encoding a secretory peptide
operatively linked to said DNA sequence
encoding a heterologous protein, wherein said
mammal is selected from the group consisting
of mouse, sheep, pig, goat and cow, and
wherein said heterologous protein is
expressed in the milk of the mammal.

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5. DeBoer's claim 7 relates exclusively to bovines, but it
recites a general regulatory promoter sequence.
6. Gordon's claim 18 refers to a set of five mammals,
including cow, which is a species of bovine, but it recites
exclusively the whey acidic protein (WAP) promoter.
7. The parties argue that each of the claims of the three
involved DeBoer patents (all of which correspond to the count)
refers to a regulatory sequence that promotes expression, a
mammary gland specific promoter, a mammary gland promoter or a
regulatory sequence from a gene that is preferentially expressed
in the mammary gland over the other tissues, or an alpha-s1
casein promoter. (JM at 2–3, ¶4.)
8. The parties argue further that each of Gordon's
involved claims specifies a DNA construct in which the promoter
is a whey acidic protein promoter (WAP) that is operably linked
to a DNA sequence encoding a heterologous protein, and a DNA
sequence encoding a signal peptide. (Id. at 3, ¶6.)
Technical background:
Testimony of Dr. Meade:
9. Dr. Harry M. Meade is Senior Vice President of Research
at GTC, an assignee of the Gordon application. (Meade
declaration, JE007 at 1, ¶2.)
10. Dr. Meade testified that he has worked and published
extensively in the fields of molecular biology and transgenic

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animal technology. (Id. at 1, ¶4.)
11. Dr. Meade testified that he is an inventor of U.S.
Patent 4,873,316, which relates to the transgenic production of
protein in milk using the casein promoter. (Id. at ¶3.)
12. Review of the face of U.S. Patent 4,873,316 shows that
Dr. Meade is one of two inventors, that its title is "Isolation
of Exogenous Recombinant Proteins from the Milk of Transgenic
Mammals," and that it was filed June 23, 1987. (JE011 at 1.)
13. Dr. Meade states that whey acid protein is specific to
rodents, and is not normally present in the milk of ruminants.
(JE007 at 3, ¶7.)
14. According to Dr. Meade, there was no evidence in 1986
that the WAP promoter would function in bovines. (Id.)
15. Dr. Meade states that, in 1986, he thought it would
have been more likely that a milk promoter from a ruminant would
facilitate expression of heterologous proteins in ruminant milk.
(Id. at ¶8.)
16. Dr. Meade further states that he is not aware of any
example of successful expression of a heterologous protein in a
transgenic animal prior to Gordon's priority date. (Id. at
3–4, ¶9.)
17. Moreover, Dr. Meade states that it was unknown whether
a promoter from one species could effectively drive expression of
a protein coding sequence from a second species in the mammary

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gland of a third species. (Id.)
Testimony of Dr. Strijker
18. Dr. Rein Strijker, a co-inventor of the involved DeBoer
patents, is also Chief Business Office at Pharming, the assignee.
(Strijker declaration, JE005 at 1, ¶1.)
19. Dr. Strijker testified that he has extensive research
experience and numerous publications in the art of eukaryotic
gene expression and transgenic animals. (Id. at ¶2.)
20. In particular, Dr. Strijker states that he was
especially familiar with the state of the art of eukaryotic
promoters in 1986, as illustrated by the defense of his thesis,
which contained a chapter on the topic, in March of that year.
(Id. at 2, ¶6.)
21. Dr. Strijker testified that many eukaryotic genes have
a highly conserved element called a TATA box about 30 base pairs
(bp) upstream from the transcription start site. (Id.)
Moreover, according to Dr. Strijker, it was well-known that
mutations of the TATA regulatory sequence resulted in "severe
reduction of transcription levels." (Id.)
22. Dr. Strijker testified further that eukaryotic genes
often have a "CAAT box" upstream from the start site, and that
mutations of this sequence also reduce transcriptional
efficiency. (Id.) Dr. Strijker testified that still other
regulatory sequences were known to exist in eukaryotic genes, but

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that it was not known which sequences were required for promoter
activity; nor was their location known. (Id. at 2–3.)
23. Dr. Strijker testified that he is unaware of anyone
having successfully expressed a heterologous protein in the milk
of a transgenic animal as of 1986. (Id. at 3, ¶7.)
24. Dr. Strijker also testified that as of 1986, "it had
not been determined which, if any promoters, "were suitable for
the task, and what if any other regulatory sequences might be
required to achieve expression in milk." (Id.)
25. Dr. Strijker states that Campbell & Rosen (JE009),
published in 1984, reports that the WAP promoter had a "very
unusual TATA box," as well as a CAAT sequence. (JE005 at 4, ¶9.)
26. Review of Campbell and Rosen confirms Dr. Strijker's
characterization: an upstream sequence, TTTAAAT, is described as
"an unusual 'TATA box,' and another upstream sequence, CAAAGTCT,
is described as "similar to the 'CAAT' box." Both sequences were
located in the upstream portions of both mouse and rat WAP genes.
(JE009 at 8694.)
27. Dr. Strijker states that he would have inferred from
the unusual TATA box structure that the WAP promoter was
"inherently extremely weak, and/or that the WAP promoter was
regulated in a manner not yet known and probably requiring one or
more additional sequences besides the TATA box and the CAAT
region." (Id.) (JE005 at 4, ¶9.)

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28. According to Dr. Strijker, nothing in Campbell & Rosen,
or in the prior art available at the time, indicated whether the
WAP gene had other regulatory promoter sequences, or where they
were. (Id.)
29. Dr. Strijker states that the Rosen et al. reference
(JE010), published March 30, 1986, reporting the failure to
observe WAP gene expression in the majority of transfectants
analyzed, is "entirely consistent with and reinforce" his
conclusions based on the unusual TATA box reported for the WAP
gene.
30. Review of Rosen confirms Dr. Strijker's
characterization of that reference: Rosen reported that WAP gene
expression was not observed in a majority of transfectants
arising from the transfection of entire rat $-casein and WAP
genes into mammary gland cells. (JE010 at 146.)
The parties' arguments
31. The parties urge that it would not have been obvious,
given what was known about the WAP promoter, to use the WAP
promoter to express a protein in bovine milk based on the broader
genera or alternative species of promoter recited in the DeBoer
claims. More specifically, they urge that nothing in the prior
art would have motivated the selection of the WAP promoter, and
that the state of the art actually taught away from using the WAP
promoter.

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32. Moreover, the parties urge that the early state of the
art of making transgenic animals in 1986 would have further
complicated matters because it would have been difficult to
distinguish problems due to inherent structural features of the
WAP promoter from general problems of expressing proteins in
transgenic animals.
33. The parties conclude that expression using the WAP
promoter, as recited in Gordon's claims, is patentably distinct
from expression using the genera of promoters or the alternative
casein promoter recited in the DeBoer claims. Accordingly, they
urge that there is no interference-in-fact.
Discussion
Test and burden of proof
"No interference-in-fact" means there is no interfering
subject matter, that one party's claims are no impediment to a
patent for the other party's claims. The movant has the burden
to prove that the other party claims a different invention from
his own." Case v. CPC Int'l, Inc., 730 F.2d 745, 750, 221 USPQ
196, 200 (Fed. Cir. 1984). In this context, "different
invention" means "patentably distinct." Aelony v. Arni, 547 F.2d
566, 570, 192 USPQ 486, 490 (CCPA 1977) ("Sections 102, 103, and
135 of 35 U.S.C. clearly contemplate where different inventive
entities are concerned that only one patent should issue for
inventions which are either identical to or not patently distinct

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from each other. . . . there is ample precedent from this court
for framing the test of interference in fact in terms of whether
two sets of claims are patentably distinct from each other.")
If either party in an interference shows that its involved
claims would have been neither anticipated nor obvious over the
other party's involved claims, then it has established that a
precondition for an interference — that the two parties are
claiming the same patentable invention — is not met. It is then
evident that the interference was declared improvidently, and
that it should be terminated.
On the merits of the joint motion
In the present case, two experts have testified as to the
state of the art of expressing heterologous proteins in milk by
transgenic techniques as of early 1986. We find that both
Dr. Meade and Dr. Striker are qualified as experts in the field
of transgenic expression of proteins in general, and as experts
in the field of the transgenic expression of proteins in milk, in
particular. Based on their patents and publications, we find
that they were experts in and knowledgeable about the state of
that art in 1986. We therefore accept and give significant
weight to their statements that they were unaware of any example
of successful expression of a heterologous protein in a
transgenic animal prior to Gordon's priority date (JE007, Meade
declaration at 3–4, ¶9), or, more specifically, unaware of anyone

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having successfully expressing a heterologous protein in the milk
of a transgenic animal as of 1986. (JE005, Strijker declaration
at 3, ¶7.) We conclude that the technical development of the
field of the inventions was at an early stage in 1986.
Consistently, Dr. Meade states that it was unknown whether a
promoter from one species could effectively drive expression of a
protein coding sequence from a second species in the mammary
gland of a third species. (JE005 at 3–4, ¶9.) Dr. Strijker's
testimony is also consistent: as of 1986, "it had not been
determined which, if any promoters, were suitable for the task,
and what if any other regulatory sequences might be required to
achieve expression in milk." (JE007 at 3, ¶7.) We conclude from
these statements that as of 1986, there was little empirical
evidence relating to the efficacy of promoters taken from one
species used in another. Thus, there was, as of the critical
date, little if any basis for predicting the results of linking
different regulatory sequences to other protein coding sequences.
Particularly relevant to the status of the WAP promoter, Dr.
Meade states that whey acid protein is specific to rodents, and
is not normally present in the milk of ruminants. (JE007
at 3, ¶7.) Moreover, Dr. Meade states that there was no evidence
that the WAP promoter would function in bovines (id.), and that,
in 1986, he thought it would have been more likely that a milk
promoter from a ruminant would facilitate expression of

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heterologous proteins in ruminant milk. (Id. at ¶8.)
Dr. Meade's statements are supported by Dr. Strijker's
description of the Campbell & Rosen reference (JE009), that this
reference reported that the WAP promoter had a "very unusual TATA
box." (JE005 at 4, ¶9.) Dr. Strijker's statement that it was
well-known that mutations of a highly conserved TATA regulatory
sequence about 30 base pairs upstream from the transcription
start site resulted in "severe reduction of transcription levels"
(id. at 2, ¶6), supports his conclusion that the unusual TATA
sequence implies that either the WAP promoter was "inherently
extremely weak, and/or that the WAP promoter was regulated in a
manner not yet known and probably requiring one or more
additional sequences besides the TATA box and the CAAT region."
(Id. at 4, ¶9.) The conclusions of Drs. Meade and Strijker are
supported by the Rosen et al. reference, published March 30, 1986
(JE010), reporting the failure to observe WAP gene expression in
the majority of transfectants analyzed. We find that the weight
of the evidence is that the WAP promoter was known to be unusual,
and that it was known that there were difficulties using it for
heterologous protein expression in mammary gland cells.
Against this background of the state of the art, we find
that, taken as prior art, DeBoer's involved claims reciting the
use of promoters generally would not have provided one of
ordinary skill in the art with a suggestion, reason, or

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motivation, or a reasonable expectation of success, to use the
WAP promoter recited in Gordon's involved claims. Thus, we hold
that Gordon's claims would not have been anticipated by, or
obvious over, DeBoer's claims; in other words, the claims of the
two parties are not drawn to the same patentable invention.
Accordingly, we find, acting on behalf of the Director of the
United States Patent and Trademark Office, that there is no
interference-in-fact.
Order
In consideration of the joint motion for no interference in
fact, it is:
ORDERED that the joint motion that there is no interference-
in-fact between any of junior party DeBoer's U.S. Patents Nos.
5,741,957, 6,013,857, and 6,140,552, and senior party Gordon's
application 08/246,259 is GRANTED;
FURTHER ORDERED that a copy of this judgment shall be given
a number and entered in the administrative files of Junior Party
DeBoer's U.S. Patents Nos. 5,741,957, 6,013,857, and 6,140,552;
FURTHER ORDERED that a copy of this judgment shall be given
a number and entered in the administrative file of senior party
Gordon's application 08/246,259;
FURTHER ORDERED that senior party Gordon's application
08/246,259 shall be returned to the examiner for further
proceedings not inconsistent with this order;

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FURTHER ORDERED that if there is a settlement agreement,
attention is directed to 35 U.S.C. § 135(c) and 37 C.F.R.
§ 1.661.
)
RICHARD E. SCHAFER )
Administrative Patent Judge ) BOARD OF PATENT
) APPEALS AND
RICHARD TORCZON ) INTERFERENCES
Administrative Patent Judge )
) INTERFERENCE
MARK NAGUMO ) TRIAL SECTION
Administrative Patent Judge )
)
Attorney for Deboer
(real party in interest:
Pharming, B.V.)
Edward J. Keeling, Esq.
Steven W. Parmelee
Mark Sandbaken
TOWNSEND AND TOWNSEND AND CREW, LLP
Attorney for Gordon
(real parties in interest:
Genzyme Corp., and United States of America
as represented by the National Institutes of Health)
Paul T. Clark, Esq.
CLARK & ELBING LLP
Backup Counsel
Richard Wagner
HAMILTON, BROOK, SMITH & REYNOLDS, P.C.