Ex Parte 5741705 et al

Board of Patent Appeals and Interferences

Jul 27, 2011

90010527 (B.P.A.I. Jul. 27, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
90/010,527 06/10/2009 5741705 VER-245Xq700 5013
7590 07/27/2011
IAN C MCLEOD
2190 COMMONS PARKWAY
OKEMOS, MI 48864
EXAMINER
PONNALURI, PADMASHRI
ART UNIT PAPER NUMBER
3991
MAIL DATE DELIVERY MODE
07/27/2011 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte KERRY GROUP, PLC
Appellant
____________

Appeal 2011-008479
Reexamination Control 90/010,527
Patent 5,741,705
Technology Center 3900
____________

Before SALLY G. LANE, RICHARD M. LEBOVITZ, and
JEFFREY B. ROBERTSON, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on the appeal by the Patent Owner of U.S. Patent
No. 5,741,705 from the Patent Examiner’s rejections of claims 1-19, 21-23,
25-27, 31-33, 35-37, 39, 40, and 44-47 in an ex parte reexamination
proceeding. The Board’s jurisdiction for this appeal is under 35 U.S.C. §§
6(b), 134(b), and 306. We affirm-in-part.
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BACKGROUND
U.S. Patent No. 5,741,705 (hereinafter “the ‘705 patent”) issued April
21, 1998. A “Request for Ex Parte Reexamination” of the issued claims of
the ‘705 patent was filed June 10, 2009, pursuant to 35 U.S.C. §§ 302-307
and 37 C.F.R § 1.510. Reexamination was ordered.
The ‘705 patent claims are directed to a method of growing eukaryotic
cells on a culture medium of hydrolyzed protein material. The hydrolyzed
protein material is said, in the patent, to be produced by the activity of
hydrolytic enzymes on a “protein raw material” which digests the protein
into smaller peptides (‘705 patent, col. 3, ll. 34-55). The material contains
peptides that comprise the amino acid L-glutamine, the latter which serves
as an energy, carbon, and nitrogen source to the eukaryotic cells (id. at col.
1, ll. 21-24). An object of the invention is said “to provide an economic
source of L-glutamine which is stable in aqueous solution” (id. at col. 2, ll.
43-46).
The ‘705 patent issued with claims 1-19. New claims 20-52 were
subsequently added during reexamination. Claims 20, 24, 28-30, 34, 38, 41-
43, and 48-52 were cancelled. Claims 1-19, 21-23, 25-27, 31-33, 35-37, 39,
40, and 44-47 are pending and stand rejected by the Examiner as follows:
1. Claims 1-19, 21-23, 25-27, 31-33, 35-37, 39, 40, and 44-47 under
35 U.S.C. § 103(a) as obvious in view of Mihara,1 Lacey,2 and Motoi;3

1 JP 2-49579 published Feb. 19, 1990 (English translation).
2 Janet M. Lacey and Douglas W. Wilmore, Is Glutamine a Conditionally
Essential Amino Acid? 48 NUTRITION REV. 8, 297-309 (1990).
3 JP H6-245790 published Sept. 6, 1994 (English translation).
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2. Claims 1-19, 21-23, 25-27, 31-33, 35- 37, 39, 40, and 44-47 under
35 U.S.C. § 103(a) as obvious in view of Roth,4 Lacey, and Motoi;
3. Claims 1-19, 21-23, 25-27, 31-33, 35-37, 39, 40, and 44-47 under
35 U.S.C. § 103(a) as obvious in view of Heeneman,5 Lacey, and Motoi;
4. Claims 21-23, 26, 35-37, and 39 as failing to comply with the
written description requirement of 35 U.S.C. § 112, first paragraph;
5. Claims 21-23, 26, 35-37, and 39 under 35 U.S.C. § 305 as
enlarging the scope of the claim(s) of the patent being reexamined.
Claims 1, 21, 25, and 32 are representative and read as follows
(underlining and brackets show amendments relative to the original patented
claimed):
1. In a method for maintaining or growing eucaryotic
cells in vitro requiring L-glutamine by use of a culture medium
[wherein the method includes culturing the cells in the culture
medium], the improvement which comprises:
(a) providing a hydrolyzed protein material containing
peptides as a mixture in the culture medium in an effective
amount which provides a main source of the L-glutamine for
the cells alone and [as the peptides of] which contains at least
20% L-glutamine by weight of the hydrolyzed protein material,
wherein:
(i) the hydrolyzed protein material is obtained by
enzymatic hydrolysis of a protein raw material with an enzyme
to form a hydrolysate, [and] separation of any insoluble
materials [are separated from a] from the hydrolysate, and then
membrane filtration of the hydrolysate, [is subjected to
membrane filtration, wherein]

4 EP 0220379 A1 published May 6, 1987.
5 S. Heeneman, N.E.P. Deutz and W.A. Buurman, The concentrations of
glutamine and ammonia in commercially available cell culture media, 166 J.
IMMUNOLOGICAL METHODS 85-91(1993).
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(ii) the hydrolyzed protein material has a free amino acid
level of less than about 15 percent of a total weight of the
hydrolyzed protein material,
(iii) the hydrolyzed protein material has an average
length of the peptides which is less than about 15 amino acids,
and
(iv) the hydrolyzed protein material contains greater than
90 percent by weight of the hydrolyzed protein material of the
peptides and the free amino acids with a molecular weight of
less than 1000 Daltons, as determined by gel permeation
chromatography: and
(b) culturing the eucaryotic cells in vitro in the culture
medium.

21. The method of claim 1 wherein the hydrolyzed
protein material has an average length of the peptides ranging
from about 9 to about 12 amino acids.

25. The method according to claim 1 wherein the
hydrolysate is subjected to membrane filtration with a
membrane having a molecular weight cut-off of 10,000
Daltons.

32. The method according to claim 1 wherein the
hydrolyzed protein material comprises (A) peptides with a
molecular weight within 1,000 Daltons to 5,000 Daltons and
(B) peptides with a molecular weight within 5,000 Daltons to
10,000 Daltons, as determined by gel permeation
chromatography.

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1. MIHARA, LACEY, AND MOTOI

Legal Principles
To decide whether a composition, device, or process would have been
obvious in light of the prior art, it must be determined whether, at the time of
invention, “a person of ordinary skill in the art would have had reason to
attempt to make the composition or device, or carry out the claimed process,
and would have had a reasonable expectation of success in doing so.”
PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1360 (Fed.
Cir. 2007) (internal citations omitted).
“[R]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness.” In re Kahn, 441 F.3d 977, 988 (Fed. Cir. 2006).
In making an obviousness determination, “it can be important to
identify a reason that would have prompted a person of ordinary skill in the
relevant field to combine the elements in the way the claimed new invention
does.” KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 418 (2007).

Findings of Fact (“FF”)
[FF1] Mihara teaches an enzymatic decomposition product for
culturing animal cells, which would be considered the same kind of material
as the “hydrolyzed protein material” recited in the claims (App. Br. 17
acknowledging that Mihara is a decomposition product) . According to
Mihara:
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The present invention provides a culture medium
containing an enzymatic decomposition product of wheat
gluten, and a culture medium combining this culture medium
with yeast extract.
The culture medium of the present invention may be any
culture medium provided that it contains at least an enzymatic
decomposition product of wheat gluten as an ingredient of a
culture medium used to culture animal cells.
(Mihara, p. 3.)
[FF2] Mihara teaches that the decomposition product comprises
glutamine in the form of a peptide, and that such form is stable upon steam-
sterilization.
The culture medium of the present invention does not
decompose glutamine even when steam-sterilized, and so does
not require replenishing glutamine, by having glutamine present
in the form of a peptide.
(Mihara, p. 13.)
[FF3] Mihara teaches that the culture medium provided a stable
source of glutamine for animal cells propagated on it.

Table 2 shows the pH of the Enzymatic Decomposition Product of Wheat
Gluten during steam sterilization and the corresponding Cell Count.
(Id. at p. 7.)

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[FF4]
The table [2 above] shows that even when steam-sterilized at
pH 2 to 8, hardly any of the glutamine in the enzymatic
decomposition product of wheat gluten is decomposed,
revealing that this decomposition product can be used stably as
an ingredient in a culture medium.
(Id.)
[FF5]
Previously, culture media containing, for example, amino acids,
vitamins, saccharides, and inorganic salts . . . have been known
as culture media for culturing animal cells. These culture
media have the drawback, however, that steam-sterilizing
degrades the glutamine in the culture media, rendering the
glutamine unusable. To correct this drawback, a culture
medium containing an L-glutamine derivative, which is stable
against heat and is used in animal cells as L-glutamine (L-
amino acid-L-glutamine), has been known (Japanese
Unexamined Patent Publication S61-271985).
(Id. at p. 2.)
[FF6] Motoi describes an oligopeptide mixture obtained by breaking
down wheat protein with a protein degrading enzymes (Motoi, p. 3-4).
[FF7] The “oligopeptide mixture obtained by the present invention
has excellent absorbability in the digestive tract and is extremely useful as a
nutritional source in cases of invasion or intestinal dysfunction” (id. at p. 4, ¶
[0001]).
[FF8] “In particular, dipeptides and tripeptides consisting of two or
three bound amino acids are highly absorbable by the digestive tract” (id. at
p. 4, ¶ [0002]).
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[FF9] Motoi describes an oligopeptide mixture with a weight average
molecular weight of 200 to 1000 (id. at p. 2), which corresponds to a
maximum of about 7.6 amino acids (App. Br. 25).
[FF10] The combined content of dipeptides and tripeptides is 50% by
weight or more (Motoi, p. 3).
[FF11] The free amino acid content is 10% by weight or less (id.).
[FF12] Example 1 shows wheat protein subjected to degradation by
two enzymes, Orientase 22BF and Orientase 90N (id. at p. 16, ¶ [0036]).
[FF13] The resulting oligopeptide mixture had a weight-average
molecular weight of 420, which is equivalent to 3.2 amino acids (id. at p. 16,
¶ [0037]; App. Br. 25).
[FF14] The combined content of dipeptides and tripeptides was
59.8% by weight of the oligopeptide mixture (Motoi, at p. 16, ¶ [0037]).
[FF15] The free amino acid content in Example 1 was 7.2% by
weight (id.).
[FF16] Example 2 shows wheat protein subjected to degradation by
one enzyme (id. at p. 17, ¶ [0038]).
[FF17] The resulting oligopeptide mixture had a weight-average
molecular weight of 540, which is equivalent to 4.1 amino acids (id. at p. 17,
¶ [0038]; App. Br. 25).
[FF18] The combined content of dipeptides and tripeptides was
50.4% by weight of the oligopeptide mixture (id. at p. 17, ¶ [0039]).
[FF19] The free amino acid content in Example 2 was 5.8% by
weight (id.).
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[FF20] Motoi discloses digesting (hydrolyzing) wheat protein at a
range of different times, temperatures, enzyme concentrations, etc. (id. at pp.
7-12, ¶¶ [0009]-[0022]).
[FF21]
[I]n particular an oligopeptide mixture with an even higher
combined content of dipeptides and tripeptides can be obtained
by the method of Example 1, in which hydrolysis with alkaline
protease is followed by hydrolysis with neutral protease.
Id. at p. 19, ¶ [0041].)
[FF22] Motoi teaches that its oligopeptide mixture could be subjected
to “filtration.” (Id. at p. 13, ¶ [0026], l. 5.)

Discussion
The Examiner found that Mihara taught a culture medium for
maintaining and growing eukaryotic cells (Ans. 11). Mihara’s medium was
characterized by the Examiner as “an enzymatic decomposition product of
wheat gluten containing peptides composed of L-glutamine residues as the
main source of L-glutamine for the cells.” (Id.) The Examiner found that
Mihara described its culture medium as “stable in solution and against heat”
without “the drawback of being degraded by steam sterilization, as does
culture medium containing the free form” of L-glutamine (id.).
The Examiner identified the difference between the subject matter of
claim 1 and Mihara as the latter publication did not disclose a hydrolyzed
protein material having the claimed glutamine content, peptide weight, free
amino acid content, peptide sizes, and peptide molecular weights (Ans. 11-
12). The Examiner also found that Mihara did not describe the medium as
being subjected to membrane filtration. However, the Examiner found that
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Motoi described a peptide mixture with the claimed protein material
characteristics and disclosed filtration of it (id. at 12-13). Motoi’s peptide
mixture was also a hydrolytic peptide digestion product as was Mihara’s and
that recited in the claims. The Examiner determined:
One of ordinary skill in the art at the time of the
invention would have found it prima facie obvious to have
substituted the peptide mixture disclosed by Motoi for an
improved peptide source of L-glutamine in the method for
maintaining and growing eukaryotic cells in vitro taught by
Mihara. The person of ordinary skill in the art at the time of the
invention would have been motivated to do so because all of
Mihara, Lacey, and Moitoi [sic] teach that L-glutamine is more
stable in solution in the form of peptides than as a free amino
acid . . . . Because both Mihara and Motoi teach enzymatic
degradation of the same material, i.e., wheat gluten, using the
same enzyme, i.e., alkaline protease, one of ordinary skill in the
art at the time of the invention would have had a reasonable
expectation that the substitution would have yielded an
improved source of L-glutamine in cell culture medium for use
in the method of Mihara.
(Ans. 13.)
In making the statement of the rejection, the Examiner stated:
Lacey teaches that L-glutamine is known to be a critical amino
acid for cells, regardless of whether they are cultured in vitro or
present in vivo within an animal, and both Lacey and Motoi
teach that di-and tripeptides containing L-glutamine are readily
absorbed and utilized by cells.
(Id.)
Appellant contends that Lacey “provides no indication that glutamine
residues in a di- or higher peptide” could be utilized by “growing cells.”
(App. Br. 20.) Furthermore, Appellant argues that Lacey’s disclosure about
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alpha-amino protected glutamine residues cannot be extended to the random
hydrolysis products of Motoi (id.).
It was not disputed by Appellant that Mihara’s enzyme decomposition
mixture is a product of “random hydrolysis” by an enzyme, and is the same
kind of material as the “hydrolyzed protein material” recited in the claims
(FF1). Mihara’s decomposition mixture was utilized by animal6 cells in cell
cultures (FF3 & FF4). Thus, Mihara provided the skilled worker with a
reasonable expectation of success that random enzyme hydrolysis products
could be used for culturing and growing animal cells, the same type of
product that is recited in claim 1. Lacey’s teaching is unnecessary to have
reached this determination. Consequently, we do not have to decide the
accuracy of Appellant’s contention that Lacy provides “no indication” that
cultured cells could utilize di- or higher peptides. Mihara alone provided the
expectation of success.
Appellant also contends that Motoi did not “in any way suggest that
its dipeptides and tripeptides (which are intended as a human nutritional
supplement) are ‘readily absorbed by cells’ in culture.” (App. Br. 21.)
The evidence supports Appellant’s contention that Motoi described an
enzymatic degradation product (“oligopeptide mixture”) of gluten as a
nutrient source for humans (FF6 & FF7), not cells grown in culture medium.
The evidence also supports the contention that Motoi’s description of the
oligopeptide mixture as having “excellent absorbability” was with respect to
absorption by the human digestive tract (Motoi, p. 4 (Industrial field)) (FF7).

6 Animal cells are a type of eukaryotic cells.
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Thus, we agree with Appellant that Motoi’s oligopeptide mixture was not
used by Motoi to grow animal cells in culture.
However, the Examiner recognized this distinction between the
claimed subject matter and Motoi. The Examiner reasoned that because
Motoi’s oligopeptide mixture was the same type of enzyme degradation
product found by Mihara to be useful as a cell media for animal cells, the
ordinary skilled worker would have had reason to use Motoi’s mixture in
Mihara’s culture method for its glutamine content and stability, and in doing
so, would have had a reasonable expectation of success (Ans. 13).
The Examiner’s reasoning is supported by the preponderance of the
evidence. While there was no explicit suggestion that Motoi’s oligopeptide
mixture be used as an animal cell culture medium, Mihara taught that a
similar composition produced by enzymatic degradation was useful for this
purpose (FF1). Because Mihara taught that enzyme protein decomposition
products could be used as a source of glutamine to successfully grow animal
cells (FF3), persons of ordinary skill in the art would have reasonably
expected that Motoi’s enzyme decomposition product could also serve as
growth medium for cultured animals cells. The required expectation of
success is provided by Mihara. PharmaStem Therapeutics, Inc. 491 F.3d at
1360. The ordinary skilled worker would have been led to use Motoi’s
composition for its expected benefit in providing a stable source of
glutamine.
As Motoi’s oligopeptide mixture is being used for its known
properties, absent unexpected results, the Examiner’s determination that it
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would have been obvious to replace Mihara’s enzyme degradation product
with Motoi’s is supported by the preponderance of the evidence of record.

Claims 1-14, 16, 21-23, 25-27, and 31-33: Membrane filtration
Claim 1 also recites:
(i) the hydrolyzed protein material is obtained by enzymatic
hydrolysis of a protein raw material with an enzyme to form a
hydrolysate, separation of any insoluble materials from the
hydrolysate, and then membrane filtration of the hydrolysate.

Claim Interpretation
Step (i) recites that the claimed “hydrolyzed protein material is
obtained by” following by a series of recited steps. One of those steps is
“membrane filtration.” Because of the “obtained by” language, we interpret
the “hydrolyzed protein material” to be a “product-by-process.” A product-
by-process limitation defines a product in terms of how it is made.
SmithKline Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1315 (Fed. Cir.
2006).
“[E]ven though product-by-process claims are limited by and defined
by the process, determination of patentability is based on the product itself.”
In re Thorpe, 777 F.2d 695, 697 (Fed. Cir. 1985). Consequently, we must
determine whether the recited process steps impart a structure or
characteristic to the product which distinguishes it from products made by
other processes.
In this case, the claim specifies that the hydrolyzed protein material is
obtained by a process that includes the step of membrane filtration. The
claim does not define the membrane filtration step or describe the
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characteristics of the membrane filter. For example, the claim does not
require the membrane filtration to remove a specific size of particles, while
retaining particles of another size. The claim does not recite the membrane’s
pore characteristics. Thus, it is not evident what difference there would be
between a filtered hydrolyzed protein material and an unfiltered material.

Analysis
The Examiner found that:
. . . while Motoi does not specifically disclose membrane
filtration as the filtration means for removing the insoluble
material from the hydrolysate (page 13, first partial paragraph),
a person of ordinary skill in the art at the time of the invention
would have found it prima facie obvious to have used
membrane filtration to separate the soluble peptides from
insoluble material in the Motoi hydrolysate, because membrane
filtration was well known in the art at the time of the invention
to be a rapid, simple, and effective means of separating
materials according to solubility and size.
(Ans. 14.)
Appellant contends that Motoi did not teach membrane filtration to
remove peptides above a certain molecular weight (App. Br. 24). This
argument is not persuasive. As discussed above, the claim does not require
the membrane filtration step to remove a particle of a specific size from the
hydrolysate. Appellant appears to be arguing a limitation that does not
appear in the claim.
Appellant also argues that “there would have been no perceived need
to additionally perform membrane filtration on Motoi's hydrolysate to
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remove high molecular weight components, since such high molecular
weight components would not be expected to be present.” (App. Br. 24.)
Once again, Appellant is attempting to distinguish the claim from the
cited prior art publication based on a limitation that does not appear in the
claim. The “membrane filtration” step does not restrict the claim to
removing components of a specific size, such as “high molecular weight
components” as argued by Appellant.

Claims 21-23 & 35-37: Average peptide length
Claims 21-23 and 35-37 recite that the hydrolyzed material comprise
peptides having an average peptide length of “from about 9 to about 12
amino acids” (claims 21 & 35), an average peptide length “of about 9 amino
acids” (claims 22 and 36), and an average peptide length “of about 12 amino
acids” (claims 23 and 37). The issue in this rejection is whether the claimed
average peptide lengths would have been obvious to a person of ordinary
skill in the art based on the disclosures of Mihara, Lacy, and Motoi.

Claim Interpretation
The claims define the recited ranges using the term of approximation
“about.” The reason that the “about” language was used in the claims was
not explained by Appellant, but it appears to be because the amino acid
lengths are reported as averages in the ‘705 patent (infra FF23 & 24) and
therefore would not necessarily average out to a whole number.
The term “about” is not defined in the ‘705 patent. Thus, we apply
the widely used rule of rounding up when the fraction is exactly 0.5 or
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above, and rounding down when it is less. The value of “about 9” is
therefore interpreted to encompass average values of from 8.5 to 9.4, and the
value of “about 12,” to average values of 11.5 to 12.4.

Analysis
The Examiner determined that the recited ranges would have been
obvious to persons of ordinary skill in the art:
absent some teaching of the criticality of the claimed ranges,
one of ordinary skill in the art at the time of the invention
would have found it prima facie obvious to have adjusted the
reaction conditions of the hydrolysis so as to achieve the recited
peptide lengths and concentrations in the resulting mixture in
order to optimize stability and efficiency of utilization by cells
in culture.
(Ans. 15.)
The Examiner did not provide adequate evidence that persons of
ordinary skill in the art would have had reason to have adjusted the
hydrolysis conditions described in the prior art to have made peptide
mixtures with the recited average peptide lengths. The Examiner stated that
the reason was “to optimize stability and efficiency of utilization by cells in
culture,” but the evidence does not support such reasoning.
At least one reason protein decomposition products were utilized by
Mihara as animal cell culture media was to provide a source of glutamine
(FF2-FF5). Mihara, however, did not disclose the average length of its
peptides in its decomposition product. However, Mihara described prior art
which utilized an L-glutamine derivative, L-amino acid-L-glutamine – a
two-amino acid peptide or dipeptide (FF5). Based on this teaching, persons
of ordinary skill in the art would have recognized that two-amino acid
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peptides comprising glutamine were stable and useful for culturing animal
cells.
Motoi taught an enzyme decomposition product comprising peptides
as a nutritional source for humans. Motoi described a maximum of an
average of 7.6 amino acids in length, with specific examples of 3.2 and 4.1
amino acids in length (FF9, FF13, & FF17). The oligopeptide mixture
comprises a minimum content of 50% dipeptides and tripeptides (FF10,
FF14, & FF18). Thus, Motoi’s disclosure of a high di- and tri-peptide
content, coupled with specific examples of 3.2 and 4.1, and a maximum of
7.6, would not have led the skilled worker to the higher peptide sizes recited
in the claims.
Moreover, Motoi’s peptides were used for nutritional purposes, not as
a culture media for animal cells (FF7). The Examiner did not provide
sufficient evidence that the peptide lengths described in Motoi would have
guided the skilled worker in choosing peptides for growing animal cells as
described in Mihara and recited in the claims.
Finally, the Examiner did not provide sufficient evidence that larger-
sized peptides would be more efficiently utilized by cultured animal cells.
To the contrary, Mihara’s teaching about dipeptides (FF5) points to smaller-
sized peptides for growing animal cells, not peptides with longer lengths,
and specifically not the claimed ranges of about 9, about 9-12, and about 12
amino acids in length.
In sum, the Examiner did not establish a reason that would have
prompted the ordinary skilled worker to have made peptides of the claimed
sizes. Kahn, 441 F.3d at 988; KSR, 550 U.S. 398 at 418. Nor did the
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Examiner establish that the specifically claimed peptide sizes would have
reasonably been expected to be effective for culturing animal cells.
PharmaStem, 491 F.3d at 1360.
For the foregoing reasons, we reverse the rejections of claims 21-23
and 35-37.

Claims 32, 33, & 44-47: High molecular weight peptide content
Claims 32, 44, and 46 recite that the hydrolyzed protein material
comprises (A) peptides with a molecular weight within 1,000 Daltons to
5,000 Daltons and (B) peptides with a molecular weight within 5,000
Daltons to 10,000 Daltons, as determined by gel permeation
chromatography. Claims 33, 45, and 47 further recite that the hydrolyzed
protein material further comprises (C) peptides with a molecular weight
greater than 10,000 Daltons, as determined by gel permeation
chromatography.
Appellant contends that Motoi seeks to maximize the low molecular
weight content of the oligopeptide mixture to components having 1-3 amino
acids, and that Motoi indicates that “substantially all of the oligopeptide
mixture components have a molecular weight much less than 1 kDa.” (App.
Br. 26.) For this reason, Appellant contends that Motoi does not suggest the
claimed range of peptides.
Motoi taught that the size (and therefore molecular weight) of the
peptide components could be reduced by using two enzymes (Example 1)
instead of only one enzyme (Example 2), where the dipeptide/tripeptide
content of the two enzyme hydrolysis product was 59.8% and the one
enzyme hydrolysis product was 50.4% (FF12-FF18). Motoi stated:
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In particular an oligopeptide mixture with an even higher
combined content of dipeptides and tripeptides can be obtained
by the method of Example 1, in which hydrolysis with alkaline
protease is followed by hydrolysis with neutral protease.
(FF21.)
Larger peptides were therefore converted into smaller peptide
components as enzyme hydrolysis was increased, indicating that hydrolysis
was not complete and that the protein material was incompletely digested.
Thus, as more protein digestion was accomplished, the molecular weights of
the peptide components were reduced. Based on these facts, the Examiner
had reasonable basis to believe that higher molecular weight components –
some of which were converted into lower molecular weight components
when the two-enzyme treatment was performed – were present in the
incompletely digested oligopeptide mixture. As the claim does not require
any specific amount of the higher molecular weight peptides A, B, and C,
the Examiner also had reason to believe that at least some peptide
components as high as those claimed were present – shifting the burden to
Appellant to show they were not. Even trivial amounts of peptides A, B, and
C would meet the claimed limitation. Thus, we affirm the rejection of
claims 32, 33, and 44-47.

Claims 17 & 25: 10 kDa membrane filtration
Claims 17 and 25 recite that the hydrolysate is subjected to membrane
filtration with a membrane having a molecular weight cut-off of 10,000
Daltons.
The Examiner found that Motoi disclosed “filtration.” (Ans. 14.) The
Examiner found, and Appellant did not dispute, that membrane filtration was
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a conventional separation technique (id. at 14 & 34). The Examiner
determined that it would have been obvious to the ordinary skilled worker to
have utilized membrane filtration since it was well known at the time of the
invention as a “rapid, simple, and effective means of separating materials
according to solubility and size.” (Id. at 14.)
The preponderance of the evidence supports the Examiner’s
determination that the claimed subject matter would have been obvious to
the ordinary skilled worker. Motoi’s oligopeptide mixture was required to
have a minimum dipeptide and tripeptide content of 50% by weight or more
and an average molecular weight of 200-1000 (FF9 & FF10). Thus, as long
as the membrane filter did not remove the desired small molecular weight
components, the objectives of Motoi would have been achieved.
Appellant contends that Motoi did not disclose “membrane” filtration.
This argument is not persuasive.
Motoi taught that its oligopeptide mixture could be subjected to
“filtration.” (FF22). It is undisputed that membrane filtration was a
convention filtration separation technique (Ans. 34). Consequently, persons
of ordinary skill in the art would have found “membrane filtration”
reasonably suggested by Motoi’s disclosure of “filtration.” The claims are
drawn to purely conventional technique. The Examiner reasonably found
that it would have been within the scope of the level of ordinary skill in the
art to choose a membrane filter of the claimed size, guided by the principle
of selecting a filter that did not retain the smaller desired molecular weight
constituents.
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We have considered Appellant’s argument that the cited prior art
publications do not suggest a particular molecular weight cut-off (App. Br.
30). We have also considered Appellant’s contention that the recited cut-off
would have been considered ineffectual and unnecessary by the skilled
worker because there would be essentially no components present in Motoi
above the 10,000 Dalton cut-off (id. at 31). However, Appellant did not
provide adequate evidence to establish that there would have been no
components in Motoi above 10,000 Daltons. Arguments of counsel cannot
take the place of evidence lacking in the record. Estee Lauder, Inc. v.
L'Oreal, S.A., 129 F.3d 588, 595 (Fed. Cir. 1997).

Claims 26 & 39: Free amino acid content
Claims 26 and 39 recite that the hydrolyzed protein material contains
free amino acids in an amount between 0.7 and 3.5 percent by weight of the
hydrolyzed protein material.
Although the examples described in Motoi comprise 7.2% and 5.8%
by weight of free amino acids (FF15 & FF19), Motoi broadly discloses a
range which is 10% by weight or less (FF11). The claimed amounts of
between 0.7% and 3.5% fall within this range. When there is a range
disclosed in the prior art, and the claimed invention overlaps or falls within
that range, there is a presumption of obviousness. In re Peterson, 315 F.3d
1325, 1329 (Fed. Cir. 2003); Iron Grip Barbell Co. v. USA Sports, Inc., 392
F.3d 1317, 1322 (Fed. Cir. 2004). Because these facts are present here, the
Examiner had sufficient evidence to establish prima facie obviousness of the
claimed subject matter.
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Appellant contends that a range lower than 5.8% is not reasonably
suggested by Motoi because Motoi’s examples show that, as the minimum
amount of dipeptide/tripeptide content increased from 50.4% to 59.8%
percent, the free amino acid content increased from 5.8% (Example 2) to
7.2% (Example 1) (FF12-FF20). Thus, Appellant contends that Motoi has a
“practical limit” of about 5.8% (App. Br. 28). That is, at the minimum
amount of dipeptide and tripeptide content of about 50% described by Motoi
(FF10), the free amino acid content is 5.8%, which is not as low as the
claimed range of 0.7-3.5%.
This argument is not persuasive.
First, Examples 1 and 2 of Motoi were not conducted under the same
enzyme digestion conditions. Example 1 was accomplished with two
enzymes (FF12). Example 2 was accomplished with one enzyme (FF16).
Thus, the examples are not comparable and do not establish a trend because
each example was conducted under different digestion conditions.
Secondly, Motoi describes a range of enzyme digestion conditions
(FF20). Given Motoi’s express disclosure of amino acid content of less than
10% by weight, the Examiner had sufficient evidence to find that persons of
ordinary skill could routinely have produced oligopeptide mixtures with a
free amino acid content within the claimed range using Motoi’s disclosure as
guidance.
Summary
We affirm the rejections of claims 1-19, 25-27, 39, 40, and 44-47.
Claims not separately argued fall together. 37 C.F.R. § 41.37(c)(1)(vii).
We reverse the rejections of claims 21-23 and 35-37.
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2. WRITTEN DESCRIPTION & RULE 305 ISSUE

Legal Principles
To satisfy the written description requirement, the inventor “must also
convey with reasonable clarity to those skilled in the art that, as of the filing
date sought, he or she was in possession of the invention.” Vas-Cath Inc. v.
Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991). In describing the
claimed invention, there is no requirement that the wording be identical to
that used in the specification as long as there is sufficient disclosure to show
one of skill in the art that the inventor “invented what is claimed.” Union
Oil Co. of Cal. v. Atlantic Richfield Co., 208 F.3d 989, 997 (Fed. Cir. 2000).
Thus, so long as a person “of ordinary skill in the art would have understood
the inventor to have been in possession of the claimed invention at the time
of filing, even if every nuance of the claims is not explicitly described in the
specification, then the adequate written description requirement is met.” In
re Alton, 76 F.3d 1168, 1175 (Fed. Cir. 1996). “[H]ow the specification
accomplishes this is not material.” In re Wertheim, 541 F.2d 257, 262
(CCPA 1976).
Claims 2, 37, and 38, which claim a solids content range of
“between 35% and 60%,” present a different question. They
clearly claim a range within the described broad range of 25%
to 60% solids; the question is whether, on the facts, the PTO
has presented sufficient reason to doubt that the broader
described range also describes the somewhat narrower claimed
range. We note that there is no evidence, and the PTO does not
contend otherwise, that there is in fact any distinction, in terms
of the operability of appellants’ process or of the achieving of
any desired result, between the claimed lower limit of solids
content and that disclosed in the Swiss application [the priority
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application which was said by Appellant to describe the
claimed range]. We see an important practical distinction
between broad generic chemical compound inventions, for
example, as in In re Ruschig, supra, in which each compound
within the genus is a separate embodiment of the invention, and
inventions like that at bar, in which the range of solids content
is but one of several process parameters. What those skilled in
the art would expect from using 34% solids content in the
concentrated extract prior to foaming instead of 35% is a
different matter from what those skilled in the art would expect
from the next adjacent homolog of a compound whose
properties are disclosed in the specification. We wish to make it
clear that we are not creating a rule applicable to all description
requirement cases involving ranges. Where it is clear, for
instance, that the broad described range pertains to a different
invention than the narrower (and subsumed) claimed range,
then the broader range does not describe the narrower range. In
re Baird, 52 CCPA 1747, 348 F.2d 974, 146 USPQ 579 (1965);
In re Draeger, 32 CCPA 1217, 150 F.2d 572, 66 USPQ 247
(1945).
Wertheim, 541 F.2d at 264-65 (CCPA 1976).

Findings of Fact (“FF”)
[FF23]
The present invention relates to a method for maintaining or
growing eucaryotic cells in vitro requiring L-glutamine by use
of a culture medium, the improvement which comprises:
providing a hydrolysed protein material containing peptides
including L-glutamine and amino acids in a mixture in the
growth medium, wherein the mixture has a free amino acid
level of less than about 15 percent by total proteinaceous
material weight, has an average length of the peptide which is
less than about 15 amino acids . . . .
(‘705 patent, col. 2, ll. 55-64.)

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[FF24]
Preferably the free amino acid level is less than about 10
percent by the total proteinaceous material weight and the
length of the peptide is less than 10 amino acids.
(Id. at col. 3, ll. 18-21.)

[FF25]
As shown in Table 2 below, the protein hydrolysate of Example 1
comprises an average peptide length (PCL) of 9.3 and a free amino acid
level (FAA) of 3.54%.

(‘705 patent, col. 7, ll. 8-37.)

[FF26]
As shown in Table 4 below, the protein hydrolysate of Example 2
comprises an average peptide length (PCL) of 11.9 and a free amino acid
level (FAA) of 0.70%.

(Id. at col. 8, ll. 6-15.)
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Claims 21-23, 35-37, and 39
The Examiner rejected claims 21-23, 35-37, and 39 for failing to
comply with the written description requirement under 35 U.S.C. § 112, first
paragraph, because the claimed peptides of “about 9 to about 12 amino
acids,” “about 9 amino acids,” and “about 12 amino acids,” were said not to
be described in the ‘705 patent. The Examiner stated that the disclosure of
peptide lengths of 9.3 and 11.9 in the examples “do not provide support for
‘about 9’ and ‘about 12’, as is presently claimed. The scope of ‘about 9’ and
‘about 12’ is broader than the scope of the specific values of 9.3 and 11.9.”
(Ans. 24).
The written description of the ‘705 patent contains the following
pertinent disclosure:
• average peptide length of less than about 15 amino acids (FF23);
• average peptide length of less than 10 amino acids (FF24);
• average peptide length of 9.3 (FF25); and
• average peptide length of 11.9 (FF26).
Based on the disclosure of a broader range of less than about 15
amino acids, and intermediate peptides of 11.9, less than 10, and 9.3 amino
acids in length, we conclude that the ‘705 patent described the narrower
claimed range of “about 9 to about 12 amino acids.” In particular, the
disclosure by the inventor of peptide lengths less than 15 and less than 10
conveys with sufficient clarity that the inventors considered average peptide
lengths within those disclosed ranges to be part of the invention. Vas-Cath,
935 F.2d at 1563-64; Alton, 76 F.3d at 1175; Wertheim, 514 F.2d at 264-65.
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The inventors’ description of a narrower range of less than 10 amino acids
which fell within the broader range of less about 15 amino acids, coupled
with specific examples of peptides having an average length of 9.3 and 11.9
amino acids, established that the inventors invented ranges in between,
including the range bounded by the exemplary 9.3 and 11.9 values.
The value of “about 9” is broader than the value of 9.3 in that it would
have been reasonably interpreted to include a range of 8.5 to 9.4 (see Claim
Interpretation section supra.). However, “about 9” is encompassed by the
expressly described ranges of less than about 15 amino acids and less than
10 amino acids (FF23 & FF24). Consequently, persons of ordinary skill in
the art would have recognized that the inventors had in their possession
peptides with an average length of “about 9.”
Similarly, “about 12” is broader than the value of 11.9 in that it would
have been reasonably interpreted to include a range of 11.5 to 12.4 (see
Claim Interpretation section supra.). However, “about 12” is encompassed
by the expressly described range of less than about 15 amino acids.
Consequently, persons of ordinary skill in the art would have recognized that
the inventors had possession of peptides with an average length of “about
12.”

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Claims 26 & 39
Claims 26 and 39 recite that the hydrolyzed protein material contains
the free amino acids in an amount between 0.7 and 3.5 percent by weight of
the hydrolyzed protein material.
The written description of the ‘705 patent contains the following
disclosure:
• free amino acid level of less than about 15 percent by total
proteinaceous material weight (FF23);
• free amino acid level of less than about 10 percent by the total
proteinaceous material weight (FF24);
• free amino acid level of 3.54% (FF25); and
• free amino acid level of 0.70% (FF26).
The ‘705 patent’s written description specifically discloses that its
compositions comprise a free amino acid content of less than 15% and less
than 10% (FF23 & FF24). The disclosure of the broader ranges, coupled
with specific examples of 3.54% and 0.7% (FF25 & FF26), reasonably
conveyed to persons of ordinary skill in the art that the inventors’ invented
intermediate ranges, including the claimed narrower range of “the free
amino acids in an amount between 0.7 and 3.5 percent by weight of the
hydrolyzed protein material.”

Rule 305 Issue
The Examiner rejected claims 21-23, 26, 35-37, and 39 under 35
U.S.C. § 305 as enlarging the scope of the claims of the patent being
reexamined. In 35 U.S.C. § 305, it is stated that “[n]o proposed amended or
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new claim enlarging the scope of a claim of the patent will be permitted in a
reexamination proceeding . . . .” The Examiner found that the claim scope
had been enlarged because subject matter in the rejected claims was not
supported by the written description of the ‘705 patent (Ans. 25). As
discussed above, this determination was erroneous. Consequently, the
rejection under § 305 is not sustainable.

REJECTIONS 2 & 3
Rejections 2 and 3 differ from rejection 1 in using the Roth or
Heeneman publication as the primary reference, rather than Mihara. Roth
describes utilizing an animal cell growth medium comprising glutamine in
dipeptide or tripeptide form (Roth, Abstract (57) & p. 1). Heeneman
describes an animal cell nutrient media with glutamine as a free amino acid
or as a dipeptide (Heeneman, pp. 85 & 90). Neither reference teaches
culturing animal cells on a hydrolyzed enzymatic protein decomposition
product as did Mihara – a required element of claim 1. Protein
decomposition products are also not described in either Lacey or Motoi for
animal cell culture media. Consequently, there would have been no reason
with an expectation of success to have utilized Motoi’s enzymatic
decomposition product for human consumption in the Roth and Heeneman
animal cell culture methods. Kahn, 441 F.3d at 988; KSR, 550 U.S. 398 at
418; PharmaStem, 491 F.3d at 1360. We reverse the rejections of claims 1-
19, 21-23, 25-27, 31-33, 35- 37, 39, 40, and 44-47 as obvious in view of
Roth, Lacey, and Motoi, and as obvious in view of Heeneman, Lacey, and
Motoi;
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TIME PERIOD FOR RESPONSE
Requests for extensions of time in this ex parte reexamination
proceeding are governed by 37 C.F.R. § 1.550(c). See 37 C.F.R. § 41.50(f).

AFFIRMED-IN-PART

bim

FOR PATENT OWNER:

IAN McLEOD
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OKEMOS, MI 48864

FOR THIRD-PARTY REQUESTER:

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