Ex Parte Harris et al

Board of Patent Appeals and Interferences

Apr 3, 2009

10119546 (B.P.A.I. Apr. 3, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte J. MILTON HARRIS, FRANCESCO MARIA VERONESE,
PAOLO CALICETI and ODDONE SCHIAVON
__________

Appeal 2009-1274
Application 10/119,546
Technology Center 1600
__________

Decided:1 April 3, 2009
__________

Before ERIC GRIMES, RICHARD M. LEBOVITZ, and STEPHEN
WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an
essentially pure polymer. The Patent Examiner rejected the claims as

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).

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indefinite and as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We
reverse on indefiniteness and affirm on obviousness.

STATEMENT OF THE CASE
The invention relates to derivatives of polyethylene glycol,
abbreviated “PEG,” that are used to modify the characteristics of other
molecules and of surfaces. (Spec. 1:8-12.) PEG was known to enhance the
solubility and stability of therapeutic proteins like enzymes. (Id. at 2:10-20.)
Appellants’ invention is a branched or multi-armed PEG derivative that can
be prepared without toxic linkages or potentially toxic fragments. (Id. at
11:16-23.) “Relatively pure polymer molecules of high molecular weight
can be created.” (Id. at 11:23-24.) After the PEG derivative or polymer
molecule is synthesized, it can be coupled to a molecule such as a protein or
enzyme or to a surface. (Id. at 12:1-3.)
Claims 96-109, 111, 112, 114-124, and 133 are on appeal.2
The Examiner rejected the claims as follows:
• claims 96-109, 111, 112, 114-124, and 133 under 35 U.S.C. § 112,
¶ 2, as indefinite because the term “essentially pure” is uncertain as to its
meaning and scope; and
• claims 96-109, 111, 112, 114-124, and 133 under 35 U.S.C.
§ 103(a) as obvious over the combined teachings of Martinez,3 Sartore,4
Veronese,5 Yoakum,6 and Abuchowski.7

2 Claims 125-132 are also pending but have been withdrawn from
consideration by the Examiner. (App. Br. 5.)
3 U.S. Patent No. 5,643,575, issued Jul. 1, 1997.
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The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 96 is representative and reads
as follows:
96. An essentially pure water-soluble polymer having the structure:

polya—P
│
R—C—Z
│
polyb—Q

wherein:
R is a nonreactive moiety,
Z is a moiety comprising a reactive site,
polya and polyb are each independently a nonpeptidic polymer,
and
P and Q each comprise a nonreactive linker absent an aromatic
ring or ester group.

FINDINGS OF FACT
1. The original Specification and claims did not use the phrase
“essentially pure.”
4 Luciana Sartore et al., Enzyme Modification by MPEG with an Amino Acid
or Peptide as Spacer Arms, 27 APPL. BIOCHEM. BIOTECHNOL. 45-54 (1991).
5 F.M. Veronese et al., Preparation and Properties of
Monomethoxypoly(Ethylene Glycol)-Modified Enzymes for Therapeutic
Applications, in Poly(Ethylene Glycol) Chemistry: Biotechnical and
Biomedical Applications 127-37 (J. Milton Harris ed., Plenum Press, New
York, 1992).
6 U.S. Patent No. 4,650,909, issued Mar. 17, 1987.
7 Abraham Abuchowski et al., CANCER THERAPY WITH CHEMICALLY
MODIFIED ENZYMES. I. ANTITUMOR PROPERTIES OF
POLYETHYLENE GLYCOL-ASPARAGINASE CONJUGATES, 7 CANCER
BIOCHEM. BIOPHYS. 175-86 (1984).
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2. Appellants’ “Summary of the Invention” states: “[r]elatively pure
polymer molecules of high molecular weight can be created.” (Spec.
11:23-24.)
3. The “Summary of the Invention” also states: “[t]hese purifiable, high
molecular weight, monofunctional compounds have many uses.”
(Spec. 15:24-25.)
4. The “Detailed Description” summarizes two chromatographic
purifications of an example polymer as follows: “For both methods of
purification, purified mPEG-disubstituted lysine of molecular weight
10,000, titrated with NaOH, showed that 100% of the carboxyl groups
were free carboxyl groups. These results indicate that the reaction was
complete and the product pure.” (Spec. 23:33 – 24:2.)
Martinez
5. Martinez described branched polymers, that include polymers
comprising PEG, “useful in extending the in vivo circulating life of
biologically active materials.” (Col. 1, ll. 6-8.)
6. Biologically active materials to be conjugated to the polymers
included proteins and enzymes. (Col. 2, ll. 25-30.)
7. According to Martinez, the branching of the polymers gives an
advantage that contrasts with the “conventional polymer conjugates.”
(Col. 2, ll. 43-47.)
8. Martinez taught that “[a]fter synthesis, the activated branched
polymers can be purified by conventional methods and reacted with
biologically active materials . . . .” (Col. 7, ll. 12-15.)
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9. Martinez taught that “[f]ollowing the reaction, the conjugate is
recovered and purified such as by diafiltration, column
chromatography, combinations thereof, or the like.” (Col. 9, ll. 27-
30.)
Sartore
10. Sartore disclosed that polyethylene glycol was finding rapidly
expanding use in biomedical applications for derivatizing enzymes of
therapeutic value. (46:1st para.)
11. Sartore described modifying arginase, an enzyme, with MPEG
(monomethoxy polyethylene glycol). (48:2nd para.)
12. Sartore described purifying the modified arginase from excess MPEG
and products of the reaction with column chromatography. (48:2nd
para.)
Veronese
13. Veronese taught that the “therapeutic value of enzymes as drugs
would be considerably increased if drawbacks such as
immunogenicity and antigenicity, rapid clearance from circulation . . .
were overcome.” (127:1st paragraph.)
14. According to Veronese, “[n]atural or artificial polymers are being
used for surface enzyme modification” including MPEG. (127:2nd
paragraph.)
15. Veronese described removing unreacted MPEG from the modified
enzyme by gel filtration [a form of column chromatography]. (129:4th
paragraph.)
Yoakum
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16. Yoakum described a purification process to produce improved
polyethylene glycol (PEG) to be used in cell fusion. (Abstract.)
17. Yoakum’s purification process removed toxic elements from the
known and impure PEG. (Abstract.)
18. According to Yoakum, PEG was known to include aldehydes and
ketones that were cytotoxic because they lyse cells. (Col. 2, ll. 53-
59.)
19. Yoakum’s purification system used ion exchange columns [a form of
column chromatography] to separate the toxins from PEG. (Col. 3, l.
65 – col. 4, l. 13.)
20. Yoakum’s purified PEG was suitable for use in human cell genetic
transfection. (Col. 1, ll. 10-13.)
Abuchowski
21. According to Abuchowski, “L-Asparaginase is commonly used in the
treatment of acute leukemias.” (175:1st para.)
22. Abuchowski reported that attaching PEG to asparaginase, an enzyme,
produced conjugates that were “active, stable, without significant
immune response, and with greatly extended plasma half-lives in
mice.” (Abstract.)
23. Abuchowski prepared SS-PEG (methoxypolyethylene glycolyl
succinimidyl succinate) for conjugation to asparaginase. (176:2nd
para.)
24. The SS-PEG was “examined for homogeneity and absence of low
molecular weight components by HPLC using the Waters apparatus
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and the Varian G-3000 PW column [a form of column
chromatography].” (176:2nd para.)
25. After reacting SS-PEG with asparaginase, the unbound SS-PEG was
removed by dialysis. (Para. bridging 176-177.)

DEFINITENESS
The Issue
The Examiner’s position is that the claim term “essentially pure” is
not defined in the Specification and the phrase “would be uncertain as to
materials permitted and excluded in combination with the claimed polymer.”
(Ans. 4 and 9-10.)
Appellants contend that the Specification’s description of purification
and characterization of the claimed polymer makes the meaning of
“essentially pure” clear to those of skill in the art. (App. Br. 11.)
The issue with respect to this rejection is whether those of ordinary
skill in the art of water soluble polymers would understand what “essentially
pure” means in light of Appellants’ specification?

Principles of Law Relating to Definiteness
The burden of precise claim drafting rests squarely upon the applicant.
In re Morris, 127 F.3d 1048, 1055 (Fed. Cir. 1997). “‘It is axiomatic that, in
proceedings before the PTO, claims in an application are to be given their
broadest reasonable interpretation consistent with the specification, . . . and
that claim language should be read in light of the specification as it would be
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interpreted by one of ordinary skill in the art.’” In re Bond, 910 F.2d 831,
833 (Fed. Cir. 1990).
When a word of degree is used without definition, the question is
“whether one of ordinary skill in the art would understand what is claimed
when the claim is read in light of the specification.” Seattle Box Co., Inc. v.
Indus. Crating & Packing, Inc., 731 F.2d 818, 826 (Fed. Cir. 1984)
(affirming district court determination that “substantially equal to” was not
indefinite). Prior art references may be “indicative of what all those skilled
in the art generally believe a certain term means ... [and] can often help to
demonstrate how a disputed term is used by those skilled in the art.”
Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1584 (Fed. Cir. 1996).

Analysis of the Definiteness Issue
According to Appellants, one of ordinary skill in the art would
understand the phrase “essentially pure” as meaning the kind or level of
purity described in the Specification. (App. Br. 9.) Appellants argue that
examples of branched polymers described in the Specification were
essentially pure “as evidenced by the NMR and chromatographic data
showing that the branched polymers were free from detectable amounts of
unreacted organic reactants, and side-products, as well as polymer
intermediates and side products.” (App. Br. 10.) The secondary references
cited in the obviousness rejection recognize removal of unreacted material
and side-products as criteria of purity, and we weigh that as evidence
supporting Appellants’ construction. (FF12; FF15; FF24; FF25.) See
Vitronics, 90 F.3d at 1584.
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The Examiner was unpersuaded, and noted instead that “[b]eing 100%
pure is different from being essentially pure.” The Examiner concluded that
the amounts and kinds of impurities tolerated by “essentially” should have
been described. (Ans. 9-10.)
We agree with the Examiner that 100% pure is different from
“essentially” pure. However, we do not agree that Appellants were required
to specify a numerical “amount” of tolerable impurities to achieve
definiteness. The terms “about” and “substantially” are commonly used in
patent terms to “‘avoid a strict numerical boundary to the specified
parameter.’” Ecolab, Inc. v. Envirochem, Inc., 264 F.3d 1358, 1367 (Fed.
Cir. 2001) (citation omitted). Appellants are using “essentially” in a similar
way.
Appellants here described their polymers as purifiable (FF2), gave
examples of purification, and described the product as pure (FF4). As to the
kinds of impurities that the Examiner concluded should have been described,
Appellants directed attention to the Specification’s NMR and
chromatography results. According to Appellants, those results evidence
purity that is free from detectable amounts of unreacted organic reactants
and side-products, as well as polymer intermediates and side-products.
(App. Br. 10.) We conclude that a person of ordinary skill in the art would
understand that “essentially pure” means the kind and degree of purity
described in the Specification: free from detectable amounts of unreacted
organic reactants and side-products, as well as polymer intermediates and
side-products. We conclude that Appellants’ claims meet the Seattle Box
criterion for definiteness. Seattle Box, 731 F.2d at 826 (“one of ordinary
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skill in the art would understand what is claimed when the claim is read in
light of the specification”).
The Examiner also argues that the term is used “at a point of novelty,
and in such case the meaning and scope of ‘essentially pure’ must be
precise.” (Ans. 10.) The second paragraph of § 112 is “essentially a
requirement for precision and definiteness of claim language.” In re
Borkowski, 422 F.2d 904, 909 (CCPA 1970) (emphasis in original). To the
extent the Examiner suggests a numeric constraint is required to achieve
precision, that requirement would be inconsistent with precedent interpreting
terms of degree. E.g., Playtex Products, Inc. v. Procter & Gamble Co.,
400 F.3d 901, 907 (Fed. Cir. 2005) (requiring a numeric constraint on terms
of degree such as “substantially” contradicts precedent interpreting such
terms); see also In re Marosi, 710 F.2d 799, 802 (CCPA 1983) (number not
needed to define “essentially free” of impurities). In the context of a given
specification, a term of degree based on a verbal description can be precise,
when construed “in light of the specification as it would be interpreted by
one of ordinary skill in the art.” Bond, 910 F.2d at 833. If “essentially pure”
is a point of novelty or nonobviousness for Appellants’ claims, the claims
can be compared to the prior art to decide those questions.

OBVIOUSNESS
The Obviousness Issue
The Examiner’s position is that Martinez taught branched polymers
having the structure claimed and taught that the polymers can be purified by
conventional methods before conjugation. (Ans. 6.) The Examiner contends
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that one of skill in the art would have found it obvious to purify Martinez’s
polymers by conventional purification methods disclosed in Yoakum,
Sartore, Veronese, and Abuchowski. (Ans. 6.) The Examiner found that a
person of ordinary skill in the art at the time of the invention would have
been motivated to purify Martinez’s polymers because the in vivo uses
Martinez described would “require purification sufficient to make the mPEG
disubstituted lysine pure enough for in vivo use.” (Ans. 6-7.)
Appellants admit that “Martinez [taught] branched polymer structures
of the type embodied by the present claims.” (App. Br. 13.) Appellants
contend that “Martinez merely suggests that the polymers described therein
can be purified,” but that Martinez did not recognize the problems
associated with purification. (Id. at 13-14, emphasis in original.) In
Appellants’ view, “[t]he real question then is, would one looking at
Martinez, in the absence of the Appellant’s disclosure, be motivated to not
only modify Martinez, but to successfully arrive at the essentially pure
polymers of the Appellant’s claims.” (Id. at 19.)
Appellants contend that the disclosures of Yoakum, Sartore,
Veronese, and Abuchowski (the secondary references) are not relevant to the
claims. (App. Br. 14-17.) The secondary references are said to concern
purification of linear, not branched polymers, and their purifications are said
to involve either unreacted PEG (Yoakum) or PEG conjugates (Sartore,
Veronese and Abuchowski). (Id.) Appellants distinguish their own claims
as branched, not linear, polymers prior to, not after, conjugation. (Id.)
Further, Inventor Harris filed a Declaration said to show by
experiment that “the method of Martinez fails to produce a purified polymer
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in any degree.” (Id. at 19-24.) Appellants argue that the Seely8 patent “is
instructive in terms of its commentary on the state of the polymer art around
the time of the Appellant’s invention,” and supports a conclusion of
nonobviousness for Appellants’ claims. (Id. at 25.) Finally, Appellants
submitted evidence alleged to show the commercial success of “branched
PEGs such as those presently claimed for two currently marketed products.”
(Id. at 26.)
The issues with respect to this rejection are:
Would one of ordinary skill in the art have been motivated to purify
Martinez’s polymers?
Would one of ordinary skill in the art have combined the PEG linear
polymer purification teachings of Sartore, Veronese, Yoakum, and
Abuchowski with Martinez’s teaching to purify a PEG branched polymer?
Would one of ordinary skill in the art have had an expectation of
success applying conventional methods of purifying linear PEG or PEG
conjugates to purifying Martinez’s branched polymers free from detectable
amounts of unreacted organic reactants and side-products, as well as
polymer intermediates and side-products?
Does Appellants’ evidence of commercial success weigh in favor of
nonobviousness?

8 U.S. Patent No. 5,935,564, which appears to have an effective filing date
Mar. 6, 1996, issued to James Ervin Seely, Aug. 10, 1999.
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Principles of Law Relating to Obviousness
Obviousness is a question of law based on fact findings. The scope
and content of the prior art are determined; differences between the prior art
and the claims at issue are ascertained; the level of skill in the art is resolved;
and objective record evidence of nonobviousness is considered. Graham v.
John Deere Co., 383 U.S. 1, 17-18 (1966). Against that background, the
obviousness or nonobviousness of the subject matter is determined. Id.; In
re Kahn, 441 F.3d 977, 985 (Fed. Cir. 2006).
Where claimed subject matter has been rejected as
obvious in view of a combination of prior art references, a
proper analysis under § 103 requires, inter alia, consideration
of two factors: (1) whether the prior art would have suggested
to those of ordinary skill in the art that they should make the
claimed composition or device, or carry out the claimed
process; and (2) whether the prior art would also have revealed
that in so making or carrying out, those of ordinary skill would
have a reasonable expectation of success.

In re Vaeck, 947 F.2d 488, 493 (Fed. Cir. 1991). “A reference is reasonably
pertinent if, even though it may be in a different field from that of the
inventor’s endeavor, it is one which, because of the matter with which it
deals, logically would have commended itself to an inventor’s attention in
considering his problem.” In re Clay, 966 F.2d 656, 659 (Fed. Cir. 1992).
A prior art reference is said to teach away from an applicant’s invention
“when a person of ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference, or would be led
in a direction divergent from the path that was taken by the applicant.” In re
Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). To establish commercial success,
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an applicant must present “hard evidence” that the commercial success is a
“direct result of the unique characteristics of the claimed invention – as
opposed to other economic and commercial factors unrelated to the quality
of the [claimed] subject matter.” In re Huang, 100 F.3d 135, 140 (Fed. Cir.
1996).

Analysis of the Obviousness Issue
It is undisputed that Martinez taught polymers having the structures
Appellants claim. (App. Br. 13.) It is undisputed that Martinez’s
unconjugated polymers were not “essentially pure.” It is also undisputed
that Martinez taught “the activated branched polymers can be purified by
conventional methods” before being conjugated to a biomolecule. (FF8, See
App. Br. 13.) Martinez taught the polymers would then be conjugated to
proteins or enzymes (FF6), for injection into a patient (FF5). We agree with
the Examiner’s finding that the intended in vivo use in a patient would have
motivated a person of ordinary skill in the art at the time to purify the
polymer before conjugating to a biomolecule.
Appellants do not dispute the importance of product purity when in
vivo use is intended, but they argue there is nothing in the record to show the
art recognized that impurities would arise. (App. Br. 24.) We disagree. The
references of record show that the art recognized that PEG chemistry
produced impurities, and the references taught removing the impurities.
(FF8; FF12; FF15; FF17; FF23.) Appellants stress that the secondary
references concern linear PEG, as if branched polymers comprising PEG
were exempt from impurities. (Id.) We decline to draw that inference in the
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absence of evidence supporting it. Martinez’s statement to use conventional
purification methods (FF8) supports an opposite finding, i.e., that PEG
chemistry involves impurities whether the PEG is linear or branched. We
note that the structure of Martinez’s “branched” polymers comprises linear
PEG moieties linked through a non-PEG linker. We have not been given
evidence that those of skill in the art would have thought the PEG used for
branched polymer synthesis, or the final product prepared for therapeutic
use, was exempt from the toxic contamination Yoakum described (FF18), or
that they expected the reactions for branched polymers would be exactly
complete leaving no unreacted PEG, unlike the reactions in Veronese
(FF15). We find that one of ordinary skill in the art would have been
motivated to use conventional purification methods to purify Martinez’s
polymers.
We turn to the second Vaeck factor, reasonable expectation of success,
and to the objective evidence of nonobviousness. Appellants’ arguments fall
in three groups: (1) that the secondary references have nothing to do with
their own invention; (2) that Martinez and the secondary references did not
provide a likelihood of success in achieving essentially pure polymers; and
(3) that commercial success weighs in favor of nonobviousness.
1. We find that the secondary references are pertinent to Martinez’s
purification disclosure and to Appellants’ claims.
A motivated person of ordinary skill in the art, wishing to follow-up
on Martinez’s statement that the polymers could be purified by
“conventional methods” (FF8), would have looked to the secondary
references for conventional purification methods. Martinez reviewed
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conventional PEG conjugation in a “Background” section. (Martinez, col. 1.
ll. 5-63.) Martinez contrasted its own branched polymer conjugates with
“the string-like structure of conventional polymer conjugates.” (FF7,
emphasis added.) We find that when Martinez said the branched polymers
can be purified by conventional purification methods, it was referring to the
purification methods in use at that time for conventional PEG conjugate
molecules. We find that Sartore (FF12), Veronese (FF15) and Abuchowski
(FF24, FF25) purified PEG conjugates and that a person of ordinary skill in
the art at the time Appellants’ invention was made would have considered
them to be in the field of “conventional purification methods” that Martinez
named. We agree with Appellants that Yoakum is not in the conjugation
field, but we find that Yoakum was reasonably pertinent to the purification
problem Martinez addressed. In particular, Yoakum’s PEG reagents were
intended for in vivo use, as were Martinez’s PEG polymers. (FF16.)
Appellants recognize that Yoakum’s goal was to provide “sterile PEG.”
(App. Br. 14.) We find that one of ordinary skill in the art at the time
Appellants’ invention was made would have considered Yoakum’s
purification method (FF19) reasonably pertinent to the problem of purifying
Martinez’s PEG polymers. See Clay, 966 F.2d at 658-59.
According to the Specification, Appellants’ “Field of the Invention”
“relates to monofunctional derivatives of poly(ethylene glycol) and related
polymers and to methods for their synthesis . . . .” (Spec. 1:8-10.) The Field
of the Invention is broad. We find linear PEG conjugates are “related
polymers.” We reject Appellants’ argument that only branched polymer
references are pertinent art, to the exclusion of prior art relating to the “Field
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of the Invention” as the Specification states it. We presume full knowledge
by the person of ordinary skill in the art of all the prior art in the field of the
inventor’s endeavor. In re Wood, 599 F.2d 1032, 1036 (Fed. Cir. 1979)
(citing the specification statement of the field of invention).
2. We find that Martinez and the secondary references provided an
expectation of success in achieving essentially pure branched polymers, free
from detectable amounts of unreacted organic reactants and side-products, as
well as polymer intermediates and side-products.
Sartore, Veronese and Yoakum taught that column chromatography
removed excess reagents, i.e., unreacted organic reactants, and by-products,
i.e., side-products, from an MPEG-protein conjugate. (FF12; FF15; FF19.)
Abuchowski taught that dialysis removed unreacted SS-PEG from a PEG-
enzyme conjugate. (FF25.) In sum, at the time of Appellants’ invention,
conventional methods for purifying PEG-protein conjugates were known.
We find that when Martinez said the branched polymer could be purified by
conventional methods, Martinez was referring to such conventional polymer
purification methods as used by Sartore, Veronese, Yoakum, and
Abuchowski. The application of those methods to purifying Martinez’s
branched polymers would have been expected to remove detectable amounts
of unreacted organic reactants and side-products, as well as polymer
intermediates and side-products, because those are the results the secondary
references reported when purifying PEG or PEG-protein conjugates.
Martinez’s disclosure that the branched polymers could be purified by
conventional methods is presumed enabled, and Appellants bear the burden
of showing that it is not. See Amgen Inc. v. Hoechst Marion Roussel, Inc.,
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314 F.3d 1313, 1355 (Fed. Cir. 2003). We agree with the Examiner that a
reasonable expectation of success is bolstered by Martinez’s further teaching
of chromatography as a conventional method to purify the conjugate. (Ans.
7; FF9.)
Appellants argue that Martinez Examples 1-6, 8 and 9 describe
polymers purified by recrystallization, but that Martinez did not confirm
purity. (App. Br. 19.) According to Martinez, the “non-limiting examples
illustrate certain aspects of the invention.” (Col. 9, ll. 39-40.) None of the
examples purport to describe purification. We accept Appellants’ argument
that recrystallization was one kind of conventional purification. However,
the Examiner’s prima facie case of obviousness is based on evidence from
several prior art references that conventional purification methods were not
limited to recrystallization and that several forms of column chromatography
were conventional. We are not persuaded by the argument that fails to
account for the prior art as a whole. Instead, Martinez must be read “for
what it fairly teaches in combination with the prior art as a whole.” In re
Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Appellants provide evidence in the Harris Declaration that when
Martinez Example 8 was followed, it did not produce the product it should
have, U-LYS-PEG. (Decl. ¶ 10.) Declarant reports that when U-LYS-PEG
was produced by other means, a recrystallized sample “exhibited a purity
that was essentially unchanged from crude mPEG-2-LYS.” (Decl. ¶ 16.)
When subjected to gel permeation chromatography, the recrystallized
product was shown to have been “contaminated with sizable quantities of the
polymeric impurities mPEG, mPEG-1-LYS, and PEG-3.” (Id.) Declarant
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Harris found that “[t]he recrystallization technique of the ‘575 patent does
not purify the branched polymer, PEG-2-LYS, to any degree,” (Decl. ¶ 17),
and “[t]he recrystallized polymers of the ‘575 patent contain sizable amounts
of polymeric impurities” (Decl. ¶ 19.) On the other hand, when crude
mPEG-2-LYS was purified by ion exchange chromatography using a DEAE
sepharose column as described in co-pending application 10/119,546,9 the
purifed product was “essentially absent any detectable polymeric
impurities.” (Decl. ¶¶ 14 and 18.)
Appellants acknowledge that the Harris Declaration was filed in
response to an anticipation rejection based on Martinez alone, not the current
obviousness rejection based on combined prior art teachings. (App. Br. 19-
20.) Again, Martinez must be read “for what it fairly teaches in combination
with the prior art as a whole.” Merck, 800 F.2d at 1097. Taking into
account that the secondary references disclosed conventional methods for
purifying PEG polymers, including various forms of chromatography, we do
not find the Harris Declaration persuasive of nonobviousness because it does
not address the secondary references.
According to Appellants, the Seely patent weighs against obviousness
because it is instructive on the state of the polymer art around the time of
Appellants’ invention. (App. Br. 25.) We find that the passage Appellants
selected from Seely simply speaks to the constant need for improving the
purity of PEG compounds. Seely is said to “describe[] knowing of no

9 Application 10/119,546 issued to Appellants Sep. 2, 2008, as U.S. Patent
No. 7,419,600, with claims to an ion exchange method of purifying a
branched polymer.
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preparative chromatographic procedures for successfully separating PEGs.”
(Id.) Appellants’ claims are not directed to preparative procedures, and the
secondary references taught the preparation of purified PEG-conjugates
separated from PEG. Contrary to Appellants’ view that Seely points away
from obviousness for their claims (id.), Seely does not “discourage[ ] from
following the path set out in [Martinez], or [lead] in a direction divergent
from the path that was taken by the applicant.” See Gurley, 27 F.3d at 553.
3. Appellants have not shown that the commercial success of
PEGASYS® or MACUGEN® weighs in favor of nonobviousness.
Commercial success is a question of fact. Graham, 383 U.S. at 17-18.
Appellants argue that if the invention were obvious, “it seems unlikely that
Nektar, the assignee of the instant patent application, would be the current
manufacturer and supplier of branched PEGs such as those presently
claimed for two currently marketed products, Pegasy[s]® and Macugen®,
rather than Enzon, the assignee of the Martinez patent.” (App. Br. 26.)
The fact that someone is making and selling something, without more,
does not support an inference that they should receive a patent. Instead, an
applicant must present “hard evidence” that the commercial success is a
“direct result of the unique characteristics of the claimed invention – as
opposed to other economic and commercial factors unrelated to the quality
of the [claimed] subject matter.” Huang, 100 F.3d at 140. We agree with
the Examiner that the evidence presented does not meet that test. (Ans. 14-
15.)
Appellants argue that their own assignee Nektar, not Enzon, provides
the branched PEG for Roche’s PEGASYS® product and Pfizer’s
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MACUGEN® product, the identity of which are said to be shown in
Exhibits H and I. (App. Br. 26.) Although not labeled “H” or “I,” we have
reviewed the product sheets Appellants attached for PEGASYS®, and
MACUGEN®. PEGASYS® is described as pegylated interferon alfa-2a, a
PEGylated inteferon. MACUGEN® is described as pegaptanib sodium, a
PEGylated oligonucleotide. As we understand the terminology, each
product appears to be a conjugate of a therapeutic agent, interferon or
oligonucleotide respectively, conjugated to PEG. However, Appellants
characterize their own claims as being drawn to unconjugated branched
polymers, not to conjugates of polymer with therapeutic agent. Appellants
provide no explanation of how commercial success of a conjugated product
relates to the unique characteristics of the claimed unconjugated polymers.
The proponent of commercial success evidence “must offer proof ‘that the
sales were a direct result of the unique characteristics of the claimed
invention.’” In re DBC, 545 F.3d 1373, 1384 (Fed. Cir. 2008), quoting
Huang, 100 F.3d at 140.
The product sheet for PEGASYS® refers to “Nektar’s unique,
branched PEG.” However, Appellants admit that Martinez taught the same
polymer structures as claimed; accordingly, the claimed structure is not a
“unique characteristic” of Appellants’ invention. Exhibits H and I, the
product sheets, do not associate Nektar’s branched PEG with the claim
phrase “essentially pure.” There is no evidence that commercial success of
the Roche and Pfizer products is a “direct result” of the claimed invention.
We find the evidence does not meet the required standard, and give it little
weight. DBC, 545 F.3d at 1384.
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Appellants provide a printout said to be competitor Enzon’s current
webpage, which they refer to as Exhibit E. In the first paragraph under the
heading “PEGylation,” the Enzon webpage says “there are five marketed
biologic products that utilize our proprietary PEG platform, two of which we
market, ADAGEN® and ONCASPAR®, and three for which we receive
royalties, PEG-INTRON®, PEGASYS®, and MACUGEN®.” Thus,
Appellants’ evidence shows that Enzon, the assignee of the Martinez patent,
is receiving royalties for the Roche and Pfizer products that Appellants’
assignee Nektar provides PEG for. It is undisputed that the Martinez patent
disclosed the structures now claimed, although the purity is disputed. Where
royalties are being paid to the assignee of the Martinez patent, it is unclear
that commercial success inures to Appellants’ invention or to licensing
arrangements. This is not the “hard evidence” required under Huang that
commercial success is due to the unique characteristics of Appellants’
invention. See DBC, 545 F.3d at 1384 (commercial success potentially
attributable to marketing factors rather than the characteristics of the
invention receives little weight).
Appellants refer to Exhibits F and G, said to describe Nektar’s
partnerships with each of Roche and Pfizer. Although listed as attachments,
we do not find these two exhibits in the record.

CONCLUSIONS OF LAW
We conclude that a person of ordinary skill in the art of water soluble
polymers could determine if a particular composition is an “essentially pure”
polymer;
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We find that one of ordinary skill in the art have been motivated to
purify Martinez’s polymers;
We find that one of ordinary skill in the art would have combined the
teachings of Sartore, Veronese, Yoakum, and Abuchowski with Martinez’s
teachings;
We find that one of ordinary skill in the art would have had an
expectation of success in using conventional purification methods to purify
Martinez’s polymers free from detectable amounts of unreacted organic
reactants and side-products, as well as polymer intermediates and side-
products;
We find that Appellants did not provide hard evidence showing
commercial success; and
We conclude that Martinez, Yoakum, Sartore, Veronese, and
Abuchowski rendered obvious Appellants’ branched polymers free from
detectable amounts of unreacted organic reactants and side-products, as well
as polymer intermediates and side-products.

SUMMARY
We reverse the rejection of claims 96-109, 111, 112, 114-124, and
133 under 35 U.S.C. § 112, ¶ 2, as indefinite; and
We affirm the rejection of claims 96-109, 111, 112, 114-124, and 133
under 35 U.S.C. § 103(a) as obvious over the combined teachings of
Martinez, Sartore, Veronese, Yoakum, and Abuchowski.

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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

cdc

NEKTAR THERAPEUTICS
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