Ex Parte Kivits et al

Board of Patent Appeals and Interferences

Apr 21, 2010

10484255 (B.P.A.I. Apr. 21, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte MARINUS KIVITS, CATHARINA GALAMA,
and ANDOR HENDRIKS
____________

Appeal 2009-011492
Application 10/484,255
Technology Center 1600
____________

Decided: April 21, 2010
____________

Before LORA M. GREEN, RICHARD M. LEBOVITZ, and
STEPHEN WALSH, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on the appeal under 35 U.S.C. 134 by the Patent
Applicant from the Patent Examiner’s rejections of claims 26 and 28-51.
The Board’s jurisdiction for this appeal is under 35 U.S.C. §§ 6(b). We
reverse.

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STATEMENT OF THE CASE
The claimed invention in this appeal is directed to methods of
extracting fractions containing growth factors from milk products, and the
products which contain the extracted growth factors.
Claims 26 and 28-51 are pending in this appeal and stand rejected by
the Examiner as follows:
1. Claims 47-50 under 35 U.S.C. § 102(a) as anticipated by Kivits
(WO 01/25276 A1, Apr. 12, 2001; also referred to by the Examiner as
“WO”) (Ans. 3);
2. Claims 26, 28-46, and 51 under 35 U.S.C. § 103(a) as obvious in
view of Kivits and Cox (Cox and Burk, Eur. J. Biochem., 197: 353-58,
1991) (Ans. 4-5);
3. Claims 26 and 28-51 on the ground of nonstatutory obviousness-
type double patenting as unpatentable over claims 16 and 21 of copending
Application No. 10/089,995 (Ans. 6); and
4. Claims 26 and 28-51 on the ground of nonstatutory obviousness-
type double patenting as unpatentable over claims 1, 2 and 5 of U.S. Patent
No. 6,010,698 (Ans. 6-7).
Claims 26, 47, and 49 are representative and read as follows:
26. A process for extracting fractions containing growth factors from
a milk product, comprising the steps of
a) recovering a basic fraction of the milk product by means of cationic
exchange chromatography;
b) contacting a solution containing the fraction obtained in step a)
with a hydrophobic interaction chromatography resin comprising a carrier
and a ligand attached to the carrier; wherein the ligand of the hydrophobic
interaction chromatography resin is one of an n-butyl group and a phenyl
group;
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c) eluting the hydrophobic interaction chromatography resin with an
eluent to obtain a fraction containing growth factor compounds; and wherein
the eluent of step c) contains substantially no alcohol.
47. A product obtainable by the process according to claim 26,
which contains more than 2000 µg TGF-β per gram protein up to 3000 µg
TGF-β per gram protein and less than 8 µg IGF-1 per gram protein; and
which contains immunoglobulins in an amount of 300 mg/g protein to 500
mg/g protein.
49. A product obtainable by the process according to claim 26
which contains at least 180 µg IGF-1 per gram protein up to 3500 µg IGF-1
per gram protein, and less than 30 µg TGF-β per gram protein; and which
contains immunoglobulins in an amount of 300 mg/g protein to 500 mg/g
protein.

ANTICIPATION BY KIVITS
Claims 47-50 stand rejected under 35 U.S.C. § 102(a) as anticipated
by Kivits (Ans. 3).
Statement of the issue
The issue in this rejection is whether Kivits describes the claimed
products comprising TGF-β and IGF-1 in specifically recited amounts.

Principles of law
“It has long been the case that an old product is not patentable even if
it is made by a new process. . . . However, a new product may be patented
by reciting source or process limitations so long as the product is new and
unobvious.” Amgen Inc. v. F. Hoffman-LA Roche Ltd., 580 F.3d 1340, 1366
(Fed. Cir. 2009).
“With respect to product-by-process claims, it is ‘well settled that the
presence of process limitations in product claims, which product does not
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otherwise patentably distinguish over the prior art, cannot impart
patentability to that product.’” SmithKline Beecham Corp. v. Apotex Corp.,
439 F.3d 1312, 1318 (Fed. Cir. 2006) (quoting In re Stephens, 345 F.2d
1020, 1023 (CCPA 1965).
“[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).
Because the hallmark of anticipation is prior invention, the
prior art reference – in order to anticipate under 35 U.S.C.
§ 102 – must not only disclose all elements of the claim within
the four corners of the document, but must also disclose those
elements “arranged as in the claim.” Connell v. Sears, Roebuck
& Co., 722 F.2d 1542, 1548 (Fed. Cir. 1983).
Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1369 (Fed. Cir. 2008).
To anticipate, one skilled in the art must be able to “at once envisage”
the claimed structure in the disclosure. In re Petering, 301 F.2d 676, 681
(C.C.P.A. 1962)).
Facts (F)
1. Kivits describes a process for extracting TGF-β and IGF-1 from a milk
product comprising the steps of:
2. “a) recovering a basic fraction from the milk product by means of
cationic exchange chromatography” (Kivits, 3:27-28);
3. “b) passing the fraction obtained in step a) over a hydroxyapatite
column” (id. at 3:29);
4. “c) eluting the hydroxyapatite column with appropriate eluents in such a
way as to obtain two separate fractions, these fractions being
i) a fraction comprising IGF-1 in the substantial absence of TGF-β;
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ii) a fraction comprising TGF-β in the substantial absence of IGF-1” (id. at
3:30-33).
5. “Hydroxyapatite has unique separation characteristics due to both
phosphate and calcium that can act as ligands.” (Id. at 6:2-3.)
6. “After the absorption step the hydroxyapatite column is eluted
sequentially with suitable eluting liquids. Possible eluents are phosphate
buffers, sodium chloride and potassium chloride solutions. For the different
fractions these eluents must have an increasing salt concentration. . . . Other
possible eluents are known to the person skilled in the art.” (Id. at 6:12-16.)
7. The following table summarizes the TGF-β and IGF-1 amounts recited in
Appellants’ claims 47-50 (F8-11), and the TGF-β and IGF-1 fractions
disclosed in Kivits (F12-F25):
TGF-β IGF-1
8. Claim 47 >2000 µg/g – 3000 µg/g < 8 µg/g
9. Claim 48 At least 2500 µg/g – 3000 µg/g < 8 µg/g
10. Claim 49 < 30 µg/g 180 – 3500 µg/g
11. Claim 50 < 10 µg/g 180 – 3500 µg/g
12. 7:13-19 >5 (ratio) 1
13. 7:13-19 >50 (ratio) 1
14. 7:13-19 >200 µg/g <40 µg/g
15. 7:13-19 “Generally, these fractions will
contain” at most 2000 µg/g

16. 10:12-14
(Example 1)
660 µg (1000 µg/g) “low” (5µg/g)
17. 11:1-3 100 µg (600 µg/g) “low” (8 µg/g)
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(Example 2)
18. 11:29-31
(Example 4)
500 µg (1100 µg/g) “low” (1 µg/g)

19. 7:21-25 1 >10 (ratio)
20. 7:21-25 1 >100 (ratio)
21. 7:21-25 <10 µg/g >50 µg
22. 7:21-25 “Typically” at most
500 µg/g
23. 10:12-14
(Example 1)
“low” (1 µg/g) 100 µg (150 µg/g)
24. 11:1-3
(Example 2)
“low” (< 1µg/g) 80 µg (120 µg/g)
25. 11:29-31
(Example 4)
“low” (3 µg/g) 80 µg (120 µg/g)

Analysis
Claims 47-50 are directed to products “obtainable” from the process
of claim 26. The products contain specific amounts of TGF-β, IGF-1, and
immunoglobulins. The phrase “obtainable by the process according to claim
26” is a product-by-process limitation.1 A product-by-process limitation
defines a claimed product in terms of how it is made. As no evidence was
provided by Appellants that the process of claim 26 imparts any

1 The “use of the word ‘obtainable’ rather than ‘obtained by’ cannot give it a
free pass to escape the ambit of the product-by-process claiming doctrine.”
Abbott Laboratories v. Sandoz, Inc., 566 F.3d 1282, 1296 (Fed. Cir. 2009).
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characteristic or feature on the product that would distinguish it from
products made by other processes, we determine the patentability of the
claims based on the product, itself.
The Examiner found that the claimed products comprising TGF-β and
IGF-1 were described on page 7, lines 15-30 of Kivits (Ans. 3). We have
considered the Examiner’s determination, but conclude that there are
insufficient findings to establish that Kivits described “all elements of the
claim within the four corners of the document, . . . ‘arranged as in the
claim.’” NetMoneyIn, 54 F.3d at 1369.
As summarized by Findings 12-18, there is no example in Kivits of a
product comprising “more than 2000 µg TGF-β per gram protein up to 3000
µg TGF-β per gram protein and less than 8 µg IGF-1 per gram protein” as
recited in claim 47 (F8). Although a fraction of at most 2000 µg TGF-β is
described (F15), Kivits does not disclose how much IGF-1 is present in it.
The Examiner found that “there is a lower amount of IGF-1 disclosed which
furthermore is within the claimed range” (Ans. 8). However, on page 7 cited
by the Examiner, the value of “<40 µg/g” IGF-1 is disclosed (F14), but this
value is not paired with the 2000 µg TGF-β value nor does it meet the
claimed value of “less than 8 µg IGF-1.” While there are examples of
products with IGF-1 values which meet the “less than 8 µg IGF-1”
limitation, the content of TGF-β is at most 1100 µg/g (F16-F18) and outside
the claimed range.
The Examiner has not provided evidence that Kivits disclosed a
product comprising “at least 180 µg IGF-1 per gram protein up to 3500 µg
IGF-1 per gram protein, and less than 30 µg TGF-β per gram protein” as in
claim 49 (F10, F19-25). Kivits discloses that “[t]ypically” products contain
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at most 500 µg IGF-1 per gram protein, meeting the corresponding IGF-1
claim limitation, but does not disclose how much TGF-β is present (F22).
All three working examples contain less than 180 µg IGF-1 per gram protein
(F23-F25) and therefore fall outside the scope of claims 49 and 50.
In sum, the Examiner did not explain how one of ordinary skill in the
art would be able to “at once envisage” the claimed product with the recited
amounts of TGF-β and IGF-1 among the different examples and
combinations disclosed in Kivits. Petering, 301 F.2d. at 681.

2. OBVIOUSNESS OVER KIVITS & COX
Claims 26, 28-46, and 51 stand rejected under 35 U.S.C. § 103(a) as
obvious in view of Kivits and Cox (Ans. 4-5).

Statement of the issue
The issue in this rejection is whether it would have been obvious to a
person of ordinary skill in the art to have extracted “growth factors from a
milk product” utilizing a) cationic exchange chromatography and b)
hydrophobic interaction chromatography, with a resin comprising a carrier
having an attached phenyl ligand, where the growth factors are eluted with
an eluent that “contains substantially no alcohol” as recited in the claims.

Principles of law
“[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.” KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
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An obviousness “analysis need not seek out precise teachings directed to the
specific subject matter of the challenged claim, for a court can take account
of the inferences and creative steps that a person of ordinary skill in the art
would employ.” Id.
The question is not whether the combination was obvious to the
patentee but whether the combination was obvious to a person
with ordinary skill in the art. Under the correct analysis, any
need or problem known in the field of endeavor at the time of
invention and addressed by the patent can provide a reason for
combining the elements in the manner claimed.
Id. at 420.
Facts
Cox
26. Cox describes “isolation” of milk growth factor (MGF), “a molecule
possessing N-terminal sequence identity to TGF-β2” (Cox, p. 353).
27. MGF was isolated by a method consisting of a combination of:
28. “strong cation-exchange chromatography” (id. at 353-54);
29. “low-pressure hydrophobic interaction [HIC] chromatography” using
phenyl-Sepharose CL-4B (id. at 353-54);
30. “hydrophobic-interaction HPLC” (id. at 353 & 355); and
31. “HPLC size-exclusion chromatography” (id. at 353 & 355).
32. After loading the phenyl-Sepharose CL-4B with the milk fractions, Cox
discloses that the “column was finally eluted by two-step isocratic procedure
with buffers containing 28% and 40% (mass/vol.) ethanol in 0.2 M
ammonium acetate respectively.” (Id. at 354, col. 2.)

Specification
33. According to the Specification,
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By “substantially no alcohol”, it is meant that the eluent of step
c) contains less than 15% (vol/vol) of alcohol, preferably less
than 5%, and more preferably contains no alcohol.
(Spec. 7, ll. 16-18.)
Analysis
The Examiner found that Kivits described using cationic exchange
chromatography to purify growth factors as in claim 26, but did not disclose
combining the claimed combination of cationic exchange chromatography
with hydrophobic interaction chromatography (“HIC”), the latter comprising
a carrier attached to a phenyl ligand (F2; Ans. 5). However, the Examiner
found that Cox taught hydrophobic interaction chromatography with a
phenyl ligand in a process of isolating a growth factor (F26, F29; Ans. 5).
The Examiner concluded:
It would have been obvious to one of ordinary skill in the
art at the time the claimed invention was made to combine the
teachings of WO [Kivits] and Cox et al to replace the calcium
ligand of WO with the phenyl ligand of Cox et al in order to
produce the growth factors. . . .
Each of the process steps are well known to those of skill
in the art and one of skill would have expected successful
results, see page 13, all lines.
(Ans. 5.)
In making an obviousness determination, the Examiner is not required
to identify explicit teachings in the prior art that would have led persons of
ordinary skill in the art to the claimed subject matter. KSR, 550 U.S. at 418.
However, the Examiner must provide a plausible reason as to why the
skilled worker would have been prompted to have made the claimed
invention. Id. In this case, the Examiner did not provide a reason to have
substituted Cox’s phenyl group containing HIC resin for Kivits’ calcium-
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containing hydroxyapatite (Ans. 10). The fact that the substitution could
have been made is not a reason to have made it.
In addition to this, the Examiner did not provide an adequate
explanation as to why, when utilizing Cox’s HIC resin, persons of ordinary
skill in the art would have had reason to modify the alcohol content of its
eluent used to elute the growth factors. Claim 26 requires that the
hydrophobic interaction column be eluted with an eluent which “contains
substantially no alcohol.” The latter phrase is defined in the Specification to
mean “less than 15% . . . of alcohol” (F33). Cox, which describes both
cationic exchange column chromatography and an HIC column with a
phenyl ligand (F28 & F29) as recited in steps a) and b) of claim 26, elutes
the column “by two-step isocratic procedure with buffers containing 28%
and 40% (mass/vol.) ethanol in 0.2 M ammonium acetate respectively. “
(F32.)
The Examiner argued:
[G]iven that the chromatography is hydrophobic and alcohol is
hydrophilic it would have been expected for the eluent to
contain little alcohol. The eluent containing substantially no
alcohol would have been expected to not interfere with the
interaction of binding the components to the resin.
(Final Rejection, dated Sept. 20, 2007, p. 5)
The Examiner did not provide factual evidence to support this
reasoning. Cox explicitly discloses that ethanol is used to elute the growth
factors from the column (F32). Thus, in the presence of ethanol, the bound
growth factor is released from the phenyl group of the HIC column resin. It
is unclear how the Examiner’s statement about the hydrophilic nature of
alcohol bears on the question of whether persons of ordinary skill in the art
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would have known that alcohol (i.e., ethanol) could be removed from Cox’s
eluent, without affecting the ability of the eluent to elute the growth factor.
The obviousness rejection of claims 26, 28-46, and 51 is therefore
reversed.

3. PROVISIONAL OBVIOUSNESS TYPE-DOUBLE PATENTING
OVER CO-PENDING APPLICATION
Claims 26 and 28-51 stand provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as unpatentable over claims
16 and 21 of copending Application No. 10/089,995 (Ans. 6). The
Examiner contends that although “the conflicting claims are not identical,
they are not patentably distinct from each other because the only difference
between the claims is scope.” (Id.)
Method claims 16 and 21 of the 10/089,995 application require a
hydroxyapatite column, but not an HIC column as recited in independent
claim 26 at issue in this appeal. The Examiner did not explain why it would
have been obvious to persons of ordinary skill in the art to have utilized an
HIC column in the method claims of the 10/089,995 application. Since the
Examiner did not meet the burden of providing a reason as to why the
claimed invention would have been obvious to one of ordinary skill in the art
in view of the 10/089,995 application, we reverse the rejection of claims 26
and 28-51.

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4. PROVISIONAL OBVIOUSNESS TYPE-DOUBLE PATENTING
OVER PATENT
Claims 26 and 28-51 stand rejected on the ground of nonstatutory
obviousness-type double patenting as unpatentable over claims 1, 2 and 5 of
U.S. Patent No. 6,010,698 (Ans. 6-7). The Examiner contends that although
“the conflicting claims are not identical, they are not patentably distinct from
each other because the only difference between the claims is scope.” (Id. at
7.)
Claim 1 of U.S. Patent No. 6,010,698, the only independent claim in
the patent, is to a process of recovering growth factors from milk or a milk
derivative comprising a step of adsorbing on to a cation exchanger, followed
by fractionated elution of the cation exchanger to obtain at least one fraction
enriched in growth factors. Claim 26 in this appeal involves cation ion
exchange chromatography and hydrophobic interaction chromatography
(HIC) having a carrier with a phenyl ligand, the latter of which is not recited
in claim 1 of the issued patent. The Examiner did not make any findings of
fact regarding HIC nor provide an explanation as to why it would have been
obvious to persons of ordinary skill in the art to have utilized an HIC column
in the method claim of the 6,010,698 patent. Since the Examiner did not
meet the burden of providing a reason as to why the claimed invention
would have been obvious to one of ordinary skill in the art in view of the
10/089,995 application, we reverse the rejection of claims 26 and 28-51.

REVERSED

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