Ex Parte Buechler et al

Board of Patent Appeals and Interferences

Jul 21, 2008

11184746 (B.P.A.I. Jul. 21, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte
KENNETH F. BUECHLER, MARIUSZ G. BANASZCZYK,
and JOSEPH BARRY NOAR
____________

Appeal 2008-3599
Application 11/184,746
Technology Center 1600
____________

Decided: July 21, 2008
____________

Before TONI R. SCHEINER, LORA M. GREEN, and
FRANCISCO C. PRATS Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s final rejection of claims 1-17. We have jurisdiction under
35 U.S.C. § 6(b). Claim 1 is representative of the claims on appeal, and
reads as follows:

Appeal 2008-3599
Application 11/184,746

1. A compound of the formula:

wherein:
X is (alkylene oxide)n;
n is between about 40 to about 450; and
Y is C1-10 alkylene straight or branched chain comprising from 0-4
backbone heteroatoms, optionally substituted with from 1 to 4 substituents
independently selected from the group consisting of C1-16 alkyl straight or
branched chain, halogen, trihalomethyl, C1-6 alkoxy, -NO2, -NH2, =O, -OH, -
CH2OH, -C(O)NH2, and a linkage to a polyalkylene oxide moiety, provided,
however, that Y is not an alkylene oxide unit.
We affirm.

DISCUSSION
Claims 1-17 stand rejected under 35 U.S.C. § 103(a) as being obvious
over the combination of Gilbert1 and Shen.2 As Appellants do not argue the
claims separately, we focus our analysis on claim 1, and claims 2-17 stand or
fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii).
The Examiner notes first that the claims are drawn to “a
heterobifunctional crosslinker comprising maleimide and N-

1 Gilbert, U.S. Patent No. 6,774,116 B2, issued August 10, 2004.
2 Shen, U.S. Patent No. 6,911,197 B2, issued June 28, 2005.
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hydroxysuccinimide (NHS) moieties linked through polymer of alkylene
oxide linker (e.g. PEG linker).” (Ans. 4.)
The Examiner then cites Gilbert for teaching “a heterobifunctional
crosslinker comprising maleimide and succinimide linked through a linker
comprising water soluble PEG polymer.” (Ans. 4.) The Examiner
specifically cites compound 21 of Figure 6, noting that Gilbert is silent as to
the structure of PEG (id.). According to the Examiner, citing Shen, the
structure of PEG is well known in the art of cross-linkers, and when it is put
into compound 21 of Gilbert, the structure is:

(Ans. 4).
The Examiner then notes that the only difference between the
compound of Gilbert and the claimed compound is the alkylene chain length
that links the succinimide ester to the alkylene moiety, as in the compound
of Gilbert it is ethylene (shown above), and in the claimed compound,
shown below, it is butylene (id. at 4-5).

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The Examiner finds that the claimed compound is a chain homologue of the
compound of Gilbert (id. at 5). The Examiner concludes:
Therefore, given the above fact that the two crosslinkers
are chain homologs and are very similar, one would obviously
expect them to show similar properties as a crosslinker. The
claimed compounds are so closely related structurally to the
homologous compounds of the reference as to be structurally
obvious therefore in the absence of any unobviousness or
unexpected properties (MPEP § 2144.08). Applicants should
note that a generic teaching is grounds for 35 USC § 103 (a)
obviousness type of rejection. In looking at the instant claimed
compounds as a whole, the claimed compounds would have
been suggested to one skilled in the art unless unobvious or
unexpected results can be shown.

(Id.)
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
The Supreme Court has recently emphasized that “the [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.” KSR
Int’l v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007). “The combination of
familiar elements according to known methods is likely to be obvious when
it does no more than yield predictable results.” Id. at 1739. Moreover, an
“[e]xpress suggestion to substitute one equivalent for another need not be
present to render such substitution obvious.” In re Fout, 675 F.2d 297, 301
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(CCPA 1982). We conclude that the Examiner has established a prima facie
case of obviousness, and we thus turn to Appellants’ arguments and
evidence in rebuttal.
Appellants argue that Gilbert does not “clearly show the actual
chemical structure of the linker moiety between the PEG polymer
(‘PEG3400’) and the succinimide functional group, and certainly do not
suggest that it be a valeric acid moiety as in the present claims.” (App. Br.
7.)
The Examiner responds by citing a search of STN (attached as an
appendix to the Examiner’s Answer) demonstrating that the compound of
Gilbert, RN 326003-46-7, is as set forth above in the rejection (Ans. 7). As
Appellants have not provided any evidence to counter the results of the STN
search, we find that the preponderance of the evidence supports the
Examiner’s finding that compound 21 of Figure 6 is as set forth in the
statement of the rejection. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422,
1427 (Fed. Cir. 1988) (explaining the general evidentiary standard for
proceedings before the Office).
Appellants further cite Harris,3 in which a variety of linkers were
tested for use in linking PEG polymer to NHS in order to form
functionalized crosslinkers (App. Br. 8). According to Appellants, Harris
teaches that the “[k]ey to the usefulness of these linkers . . . is their
hydrolysis rate in water.” (Id.) Harris, Appellants assert, tested a PEG
polymer attached to NHS through an acetic acid linker (two carbon ester), a
propionic acid linker (three carbon ester), and a butanoic acid linker (four
carbon ester) (App. Br. 8 (citing Harris, Table 1, col. 8, ll. 1-27)).

3 Harris, U.S. Patent No. 5,672,662, issued September 30, 1997.
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Appellants note that Harris found that the acetic acid moiety had a half-life
of 0.75 minutes, which is too fast to be useful for conjugation to biologically
active substances or surfaces; the three carbon ester had a half-life of 16.5
minutes, which Harris characterized as optimal; and the four carbon ester
had a half-life of 23.3 minutes, which was considered barely acceptable
(App. Br. 8-9). Harris, Appellants argue, did not test or suggest using a
valeric acid moiety, and moreover, “a skilled artisan would not be motivated
to modify the 3 carbon propionic acid or 4 carbon butanoic aid [sic] linker
moiety to a 5 carbon valeric acid moiety because the trend with 2-4 carbons
provides an expectation of unsatisfactory results.” (App. Br. 9.)
Elaborating further, Appellants assert that the “logical presumption
from the statement in Harris [ ]—that a 4 carbon linker ‘is less reactive than
the [3 carbon] propionic acid, but is still of utility . . .—is that a longer 5
carbon linker would no longer be ‘of utility’ as part of a bifunctional
crosslinker.” (Id.) Contrary to the expectation provided by the data in
Harris, Appellants argue that “the claimed molecule usefully forms
maleimide-functionalized BSA-latex particles for which the BSA is later
substituted for a biologically active Fab fragment,” which utility would not
have been predicted from Harris (id. at 9-10). Appellants assert further that
the results in Harris “are clearly at odds with the Examiner’s position that
‘there is a presumed expectation that such compounds [chain homologs]
possess similar properties.’” (Reply Br. 5 (alterations in original).)
Table 1 of Harris, relied upon by Appellants, is reproduced below:
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(Harris, col. 8). The Table presents the half-lives for hydrolysis of a series
of PEG-NHS esters (col. 8, ll. 1-2), wherein a half-life of 10 to about 20 or
25 minutes is generally desirable (id. at ll. 36-37).
Compound 10 is the acetic acid ester (two carbon ester, 0.75 minute
half-life); compound 4 contains the propionic acid linker (three carbon ester,
16.5 minute half-life); and compound 1 contains the butanoic acid linker
(four carbon ester, 23.3 minute half-life). Thus, Harris teaches each of the
esters in the series leading up to the claimed ester.
Harris teaches further that the butanoic acid linker is less reactive than
the propionic acid linker, but is still of utility (col. 4, ll. 5-7). Harris also
teaches that the half-life is sensitive to pH (see Table 1, noting that “[a]s a
rough rule of thumb the half life triples upon lowering the pH one unit.”).
Finally, as noted by the Examiner (Ans. 10), there is not a linear relationship
between the number of carbon atoms in the acid linker and the half life.
Thus, given the facts that the butanoic acid moiety has utility as a linker, that
there is not a linear relationship between the number a carbon atoms in the
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acid linker and the half life, and that the half life itself is sensitive to pH, we
conclude that the ordinary artisan would expect the valeric acid linker as
claimed to have similar utility as a cross-linker. We also note that
Appellants have not provided any evidence specific to the use of the valeric
acid linker, other than that which they would like us to infer from Table 1 of
Harris.
Note as to Appellants’ argument that the results in Harris are at odds
with the Examiner’s position that the chain homologs possess similar
properties, Harris actually supports the Examiner’s position, as the chain
homologs do have the similar (i.e., not exactly the same) property as being
useful as a cross-linker.

CONCLUSION
In summary, we conclude that the Examiner has set forth a prima
facie case that claims 1-17 are obvious over the combination of Gilbert and
Shen, which rejection has not been adequately rebutted by Appellants, and
the rejection is thus affirmed.
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

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