Ex Parte Berg

Board of Patent Appeals and Interferences

Sep 16, 2010

10704330 (B.P.A.I. Sep. 16, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte RICHARD A. BERG
____________

Appeal 2010-001516
Application 10/704,330
Technology Center 1600
____________

Before ERIC GRIMES, DONALD E. ADAMS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL1
This appeal under 35 U.S.C. § 134 involves claims 1-11, the only
claims pending in this application. We have jurisdiction under 35 U.S.C. §
6(b).

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
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STATEMENT OF THE CASE
The claims are directed to a method for preparing human collagen or
human procollagen (claims 1 and 2), an expression system (claims 3 and 4),
a fertilized nonhuman mammalian egg (claims 5 and 6), a mouse embryonic
stem cell (claims 7 and 8), a transgenic nonhuman mammal (claims 9 and
10) and a polynucleotide (claim 11). Claim 11 is representative and is
reproduced in the “Claims Appendix” of Appellant’s Brief (App. Br. 15).
Appellant has waived any appeal of the obviousness-type double
patenting rejections (App. Br. 13). Accordingly, we decline to address the
merits of the obviousness-type double patenting rejections. The rejections
presented for review follow:
1. Claims 1-11 stand rejected under 35 U.S.C § 103(a) as unpatentable over
the combination of Bühler2 and Khillan3.
2. Claims 1, 3, 5, 7, 9, and 11 stand rejected under 35 U.S.C § 103(a) as
unpatentable over the combination of Bühler and Lee4.
3. Claims 3-11 stand rejected under 35 U.S.C § 103(a) as unpatentable over
the combination of Krimpenfort5 and Khillan.

2 Bühler et al., Rabbit β-CASEIN PROMOTER DIRECTS SECRETION OF
HUMAN INTERLEUKIN-2 INTO THE MILK OF TRANSGENIC RABBITS,
8 Biotechnol. 140-143 (1990).
3 Khillan et al., Transgenic Mice That Express a Mini-gene Version of the
Human Gene for Type I Procollagen (COL1A1) Develop a Phenotype
Resembling a Lethal Form of Osteogenesis Imperfecta, 266 J. Biol. Chem.
23373-23379 (1991).
4 Lee et al., Construction of a Full-length cDNA Encoding Human Pro-α2(I)
Collagen and Its Expression in Pro-α2(I)-deficient W8 Rat Cells, 263 J.
Biol. Chem. 13414-13418 (1998).
5 Krimpenfort et al., Generation of Transgenic Dairy Cattle Using ‘In Vitro’
Embryo Production, 9 BIOTECHNOLOGY 844-847 (1991).
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4. Claims 3, 5, 7, 9, and 11 stand rejected under 35 U.S.C § 103(a) as
unpatentable over the combination of Krimpenfort and Lee.
5. Claims 1-11 stand rejected under 35 U.S.C § 103(a) as unpatentable over
the combination of Strijker6 and Khillan.
6. Claims 1, 3, 5, 7, 9, and 11 stand rejected under 35 U.S.C § 103(a) as
unpatentable over the combination of Strijker and Lee.
We affirm.
ISSUE
Does the preponderance of evidence on this record support a
conclusion of obviousness?
FINDINGS OF FACT
FF 1. Appellant’s “invention provides recombinant production of human
collagen in a form that permits isolation of a homogeneous collagen type
and can be designed to effect the production of commercially practical
amounts of these proteins at a reasonable cost” (Spec. 3: 11-13).
FF 2. Appellant discloses that either collagen or procollagen is obtained
depending on the presence or absence of suitable proteases in the cell and
that “[i]f procollagen is secreted into the milk, of course, by supplying the
appropriate proteolytic enzymes, collagen will result” (Spec. 3: 25 - 4: 4 and
4: 17-18).
FF 3. Appellant discloses that
[T]echniques for construction of appropriate host vectors
containing regulatory sequences effective to produce foreign
proteins in mammary glands and cause the secretion of said
protein into milk are known in the art. In addition, techniques

6 Strijker et al., Expression of Human Lactoferrin in Milk of Transgenic
Animals, Conference Proceedings Series - American Chem. Soc. 38-41
(1992).
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for constructing transgenic mammals containing these systems,
including mice as well as larger mammalian species such as
cows, sheep and goats, are well known.

(Spec. 8: 11-15.)

FF 4. Bühler teaches “a construct comprising a nucleic acid sequence
encoding a human protein operably linked to the β-casein promoter” that
was used to “obtained a transgenic rabbit . . . that expressed and secreted the
human protein into the milk” (Ans. 5).
FF 5. Bühler does not teach a construct encoding a human collagen or
procollagen (Ans. 5).
FF 6. “A well developed system for use in . . . [Appellant’s] method utilizes
milk production in cows. This system is summarized by Krimpenfort”
(Spec. 7: 10-11; see also Ans. 9-10).
FF 7. Strijker teaches the “Expression of Human Lactoferrin in Milk of
Transgenic Animals” (Strijker, Title).
FF 8. Bühler, Krimpenfort, and Strijker fail to teach a construct encoding a
human collagen or procollagen (Ans. 5, 10, and 14).
FF 9. “Collagen is a well studied protein . . . [and t]he genetic materials for
use in the method of . . . [Appellant’s] invention encoding the desired
collagens are available” (Spec. 5: 4 and 6: 6-7).
FF 10. Khillan teaches “Transgenic Mice That Express a Mini-gene Version
of the Human Gene for Type I Procollagen” (Khillan, Title; see also Ans. 5-
6 and Spec. 2: 17-18 (Khillan teaches “transgenic mice . . . that express a
minigene version of the human gene for type I procollagen systemically”).
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FF 11. Lee teaches “a Full-length cDNA encoding Human Pro-α2(I)
Collagen” (Lee, Title; see also Ans. 8 and Spec 9: 8-11 (Lee teaches the
isolation of a full-length cDNA for the alpha-2 chain of type I collagen).
FF 12. Toman declares that “[t]here are a host of reasons why one would not
have expected Meade’s method to be amenable to mammary specific
expression of human collagen” (Toman Dec. 7 1: ¶ 3).
FF 13. Toman declares that “one of ordinary skill in the art at the time of
filing of the subject application, would not have had a reasonable
expectation of successfully obtaining mammary specific expression of
human collagen as instantly claimed” (Toman Dec. 2: ¶ 4).
ANALYSIS
The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 11 is representative.
The arguments presented for each obviousness rejection in
Appellant’s Brief are identical. Accordingly, we address all rejections
together.
Appellant contends that “no one had been able to effect targeted
expression of collagen in a cell which does not normally make it (such as
breast tissue)” (App. Br. 4-5). In support of this contention, Appellant
contends that Bühler, Krimpenfort, and Strijker teach the expression of
small, globular proteins in mammalian milk (App. Br. 5). We are not
persuaded. Bühler’s teaching of the expression of human interleukin-2; and
Krimpenfort and Strijker’s teaching of the expression of human lactoferrin

7 Toman Declaration, executed May 19, 1998 (Toman Dec.). We note that
the Toman Declaration was submitted in the record of Application No.
08/485,194 (see Toman Dec., Caption).
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in the milk of a transgenic animal is not evidence of a failure of others to
express collagen in a cell such as breast tissue. To the contrary, as Appellant
discloses, and established by Bühler, Krimpenfort, and Strijker
[T]echniques for construction of appropriate host vectors
containing regulatory sequences effective to produce foreign
proteins in mammary glands and cause the secretion of said
protein into milk are known in the art. In addition, techniques
for constructing transgenic mammals containing these systems,
including mice as well as larger mammalian species such as
cows, sheep and goats, are well known.

(FF 3.) More clearly, Appellant discloses that Krimpenfort summarizes a
well developed system to express human proteins in milk (FF 6).
Nevertheless, with reference to the Toman Declaration Appellant
contends that there are “numerous reasons why one skilled in the art would
not in fact have expected the cited method to be amenable to mammary
specific expression of human collagen” (App. Br. 5). We are not persuaded.
Contrary to Appellant’s contention Toman does not declare that one of
ordinary skill in the art would not have expected to observe expression of
collagen or procollagen in the milk of animals produced by any of Bühler,
Krimpenfort, or Strijker’s methodologies. Instead, Toman declares that
“[t]here are a host of reasons why one would not have expected Meade’s
method to be amenable to mammary specific expression of human collagen”
(FF 12 (emphasis added)). Appellant has failed to establish that the
rejections on this record rely on Meade’s methodology. In this regard, we
recognize that Appellant expressly discloses that Krimpenfort’s
methodology is useful in expressing proteins, including collagen, in milk
(FF 6).
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We are also not persuaded by Toman’s statement that “one of
ordinary skill in the art at the time of filing of the subject application, would
not have had a reasonable expectation of successfully obtaining mammary
specific expression of human collagen as instantly claimed” (FF 13).
Toman’s conclusion relies on the differences between fibroblasts and
mammary cells (Toman Dec. 2: ¶ 4), but Bühler, Krimpenfort, and Strijker
provide evidence that those differences did not prevent expression of human
proteins in the mammary cells of transgenic animals (FF 4, 6, 7). The
evidence cited therefore does not support Toman’s conclusion.
Further, Appellant discloses that techniques, such as those taught by
Bühler, Krimpenfort, and Strijker, for construction of appropriate host
vectors containing regulatory sequences effective to produce foreign
proteins in mammary glands and cause the secretion of said protein into milk
are known in the art (FF 3). Appellant has failed to establish that a person of
ordinary skill in this art would have had no reasonable expectation of
success in applying these known methods to obtain collagen or procollagen
from milk. In this regard, we note that Appellant discloses that either
collagen or procollagen is obtained depending on the presence or absence of
suitable proteases in the cell and if procollagen is secreted into milk,
collagen can be obtained by supplying the appropriate proteolytic enzymes
(FF 2).
Appellant contends that “Khillan did not even teach how to ‘express’
anything resembling true ‘collagen’ or ‘procollagen’. The ‘mini-gene’
expressed by Khillan lacked the large central region of collagen” (Reply Br.
3). We are not persuaded. The Specification does not define what is
required for a given protein to be considered a “human collagen” or “human
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procollagen” and Khillan refers to its sequence as a “mini-gene version” of
the human type I procollagen gene (see FF 10). Appellant has failed to
establish that Khillan’s mini-gene version of collagen is outside the scope of
the claimed collagen or procollagen (see FF 10).
With regard to Lee, Appellant contends that Lee’s “host W8 cells do
normally secrete collagen” (Reply Br. 4). While this may be true, Appellant
has failed to provide persuasive evidence or reasoning to support a
conclusion that it would not have been prima facie obvious to a person of
ordinary skill in this art to utilize the collagen teachings of Khillan and Lee
in combination with the teachings of Bühler, Krimpenfort, or Strijker to
produce a construct comprising a nucleotide sequence encoding human
collagen or human procollagen operably linked to a promoter of a milk-
specific protein with a reasonable expectation that the expression product of
such a construct would be expressed in the milk of a transgenic animal
containing the construct.
CONCLUSION OF LAW
The preponderance of evidence on this record supports a conclusion
of obviousness.
The rejection of claim 11 under 35 U.S.C § 103(a) as unpatentable
over the combination of Bühler and Khillan is affirmed. Claims 1-10 fall
together with claim 11.
The rejection of claim 11 under 35 U.S.C § 103(a) as unpatentable
over the combination of Bühler and Lee is affirmed. Claims 1, 3, 5, 7, and 9
fall together with claim 11.
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Application 10/704,330

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The rejection of claim 11 under 35 U.S.C § 103(a) as unpatentable
over the combination of Krimpenfort and Khillan is affirmed. Claims 3-10
fall together with claim 11.
The rejection of claim 11 under 35 U.S.C § 103(a) as unpatentable
over the combination of Krimpenfort and Lee is affirmed. Claims 3, 5, 7,
and 9 fall together with claim 11.
The rejection of claim 11 under 35 U.S.C § 103(a) as unpatentable
over the combination of Strijker and Khillan is affirmed. Claims 1-10 fall
together with claim 11.
The rejection of claim 11 under 35 U.S.C § 103(a) as unpatentable
over the combination of Strijker and Lee is affirmed. Claims 1, 3, 5, 7, and
9 fall together with claim 11.

TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

alw

RICHARD ARON OSMAN
3525 DEL MAR HEIGHTS RD. #915
SAN DIEGO, CA 92130