Ex Parte Yu et al

Patent Trial and Appeal Board

Sep 16, 2016

11566141 (P.T.A.B. Sep. 16, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111566,141 12/01/2006
20995 7590 09/20/2016
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE, CA 92614
FIRST NAMED INVENTOR
Lei Yu
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
NDTC0.053A 5406
EXAMINER
ROGERS, JAMES WILLIAM
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
09/20/2016 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
j ayna.cartee@knobbe.com
efiling@knobbe.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte LEI YU, GANG ZHAO, SANG VAN, SANJIB KUMAR DAS,
ZHONGLING FENG, XIAOLI FU, XINGHE WANG, YI JIN, and
FUCHEN1
Appeal2014-008366
Application 11/566, 141
Technology Center 1600
Before JOHN G. NEW, RICHARD J. SMITH, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to polymer
conjugates for use in cancer treatment. The Examiner has entered rejections
for obviousness and non-statutory double patenting. We have jurisdiction
under 35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the Real Party in Interest as Nitto Denko Corporation
of Japan. App. Br. 3.
Appeal2014-008366
Application 11/566, 141
STATEMENT OF THE CASE
Background
The Specification discloses "[a]dministered hydrophobic anticancer
drugs and therapeutic proteins and polypeptides often suffer from poor bio-
availability. Such poor bio-availability may be due to incompatibility of bi-
phasic solutions of hydrophobic drugs and aqueous solutions and/or rapid
removal of these molecules from blood circulation by enzymatic
degradation." Spec. i-f 6. The Specification discloses "[t]his invention
relates generally to biocompatible water-soluble polymers with pendant
functional groups and methods for making them, and particularly to
polyglutamate amino acid conjugates useful for a variety of drug,
biomolecule and imaging agent delivery applications." Id. i-f 2.
The Specification discloses "polyglutamate-amino acids that are
capable of conjugating to a number of agents, such as imaging agents and/or
drugs." Id. ,-r 14.
The Specification discloses "[a]n embodiment provides a polymer
conjugate comprising a recurring unit of the formula (I) and a recurring unit
of the formula (II):
0
t jj Ht c~o+--N J .
vH., I .
CH~
I
c=o
I ()., r{\ .!/
1 \J~.4vR2
!.;.. I
_,/'
R'
(l) (U)
2
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Application 11/566, 141
Spec. i-f 58.
The Specification discloses "[a] broad variety of other recurring units
may be included in the polymer conjugate with the recurring unit of formula
(I) and the recurring unit of formula (II). In an embodiment, the polymer
conjugate further comprises a recurring unit of the formula (III):
(Ill)
Spec. i-f 65.
The Specification discloses "[p ]aclitaxel ... is a FDA-approved dn.1g
for the treatment of ovarian cancer and breast cancer. However, like other
anti-cancer drugs, paclitaxel suffers from poor bio-availability due to its
hydrophobicity and insolubility in aqueous solution." Id. i-f 9.
The Specification discloses "[i]n an embodiment, the anticancer drug
may be selected from the group consisting of a taxane, camptothecin, and
doxorubicin. When the agent comprises a taxane, it is preferable that the
taxane is paclitaxel or docetaxel." Id. i-f 68.
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Application 11/566, 141
Rejections
The following rejections are before us to review (Ans. 2):
A. Claims 1, 2, 9, 10, 16-18, 20-22, 25-37, 42, 43, and 48-55 are
rejected under 35 U.S.C. § 103(a) as being unpatentable over
Bichon2 in view of Xu. 3
B. Claims 1, 2, 9, 10, 16-18, 20-22, 25-37, 42, 43, and 48-55 are
rejected under 35 U.S.C. § 103(a) as being unpatentable over
Bichon and Li. 4
C. Claims 1, 2, 9, 10, 16-18, 20-22, 25-37, 42, 43, and 48-55 are
rejected on the ground of nonstatutory obviousness-type double
patenting as being unpatentable over claims 1-32 of Application
Serial No. 12/019,612.
D. Claims 1, 2, 9, 10, 16-18, 20-22, 25-37, 42, 43, and 48-55 are
rejected on the ground of nonstatutory obviousness-type double
patenting as being unpatentable over claims 1-20 of Application
Serial No. 12/117,678.
E. Claims 1, 2, 9, 10, 16-18, 20-22, 25-37, 42, 43, and 48-55 are
rejected on the ground of nonstatutory obviousness-type double
patenting as being unpatentable over claims 1-19 of copending
Application No. 12/117,601, now U.S. Patent. 8, 197,828.
Representative Claims
Claims 1, 2, 9, 10, 16-18, 20-22, 25-37, 42, 43, and 48-55 are on
appeal. 37 C.F.R. § 41.37(c)(l)(vii). Claim 1 illustrates the appealed
subject matter and reads as follows:
2 U.S. Pat. No. 4,892,733, published Jan. 9, 1990.
3 U.S. Patent Publication No. 2004/0121954 Al, published June 24, 2004.
4 U.S. Patent No. 6,441,025 B2, published Aug. 27, 2002.
4
Appeal2014-008366
Application 11/566, 141
1. A polymer conjugate comprising a recurring unit of the formula (I)
and a recurring unit of the formula (II):
wherein:
each n is 2;
(I)
each A 1 is oxygen;
each A 2 is oxygen;
~ 1 • 1•' 1
K' 1s pac11taxe1;
(ll)
R2, R3, and R4 are each independently hydrogen or an alkali
metal;
wherein the polymer conjugate comprises an amount of the
paclitaxel in the range of about 5 to about 40% (weight/weight) based
on the mass ratio of the paclitaxel to the polymer conjugate;
wherein the number of recurring units of formula (I) and
recurring units of formula (II) is in the range of from about 100 to
about 2,000; and
wherein the amount of the paclitaxel, the percentage of the
recurring unit of the formula (I) and the percentage of the recurring
unit of the formula (II) are selected to provide a polymer conjugate
solubility that is greater than that of a comparable polyglutamic acid
conjugate that comprises substantially the same amount of the
paclitaxel, the polymer conjugate solubility being greater when a
tested polymer conjugate solution, comprising at least 5 mg/mL of the
polymer conjugate in 0.9 wt.% aqueous NaCl at about 22°C, has
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Appeal2014-008366
Application 11/566, 141
greater optical clarity over a broader pH range than that of a
comparable tested polyglutamic acid conjugate solution.
OBVIOUSNESS
Appellants do not separately argue the rejections of claims 1, 2, 9, 10,
16-18, 20-22, 25-37, 42, 43, and 48-55 as obvious over Bichon and Xu and
Bichon and Li. App. Br. 10-20. Accordingly, we will consider these
rejections together.
In rejecting claims 1, 2, 9, 10, 16-18, 20-22, 25-37, 42, 43, and 48-
55 as obvious over Bichon and Xu and Bichon and Li, the Examiner cited
Bichon as teaching biodegradable polypeptide derivatives of polyaspartic
acid and/or glutamic acid of the formulas:
Ans. 3--4. The Examiner found the polymer of Bichon specifically
exemplifies polyglutamic acid (PGGA) where m in the formula I above is
selected to be 0 and n = 2. Id. at 4. The Examiner found Bichon teaches
"that the polymers have excellent solubility and provide good control of
degradation." Non-Final Rej. 4. 5 The Examiner found "Bichon teaches that
5 Mailed July 12, 1013.
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Application 11/566, 141
the [molecular weight] of the peptide should be at least 5,000 Daltons or
more, calculated to be [approximately] 39 monomer repeat units, thus
Bichon teaches about 39 to any number of repeat units." Non-Final Rej. 4.
The Examiner found Bichon suggests substituting the polypeptides
with anticancer drugs: "drugs, including anticancer agents, may be
covalently bound to the polymers of formulas I and II above for treatment of
diseases such as cancer. The reaction scheme is shown below, where Mis a
drug":
Id. The Examiner found [t]he repeat units that comprise the [molecular
vveight] recited in Bichon encompass and overlap applicants claimed number
of repeat units" and "the preparation of polypeptide conjugates having [a]
variable amount of monomer with varying molecular weight is within the
level of skill of one having ordinary skill in the art at the time of the
invention." Id.
The Examiner found "Xu teaches treatment of various cancers by
administering polyglutamic acid conjugate drug carriers" and that the drugs
"included paclitaxel which [is] covalently attached to the polymer through
the free carboxylic acid side chain of glutamic acid." Id. at 5. The
Examiner found Xu disclosed that "paclitaxel could comprise about 20 to
about 40 wt% of the total polypeptide carrier." Id.
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The Examiner found Li teaches "a treatment for various cancers
comprising administering polyglutamic acid conjugate drug carriers" and
that the drugs "were covalently attached to the polymer through the free
carboxylic acid side chain of glutamic acid." Id. at 7. The Examiner further
found Li taught the use of paclitaxel conjugated to polyglutamic acid and
comprising "any value from about 1 to about 40 wt% (including about 35
wt%) of the total polypeptide carrier." Id.
The Examiner concluded that because Bichon expressly suggested the
substitution of the polypeptides with anticancer drugs, one of ordinary skill
in the art would have had a "high expectation of success in substituting the
glutamyl glutamines of Bichon with the anticancer drug paclitaxel, in the
same amounts described by Xu" (Non-Final Rej. 5) or the amounts
described by Li (id. at 7). The Examiner found the ordinary artisan would
have a high expectation of success in producing a poly(glutamyl glutamine)
paclitaxel conjugate because the "reaction site between glutamyl glutamine
and paclitaxel is the same (COOR on peptide and OH on paclitaxel) as the
reaction site between the drug and polyglutamic acid" for both the
combination of Bichon and Xu (id. at 5---6) and Bichon and Li (id. at 7-8).
The Examiner found the ordinary artisan would be motivated to modify
Bichon's conjugate to create a soluble paclitaxel-polymer conjugate able to
provide controlled release of paclitaxel in order to treat a cancer that is
treatable with paclitaxel, using either the monomer peptide disclosed in Xu
(id. at 6) or the monomer peptide disclosed in Li (id. at 8).
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Appeal2014-008366
Application 11/566, 141
The Examiner found the ordinary artisan would have found it obvious
"to add the monomers described in Xu with the monomers of Bichon to form
a copolymer containing monomeric units of both glutamyl glutamine and
glutamic acid" because both monomers are peptides that are similar in
structure. Non-Final Rej. 6. The Examiner found an ordinary artisan would
have "a high expectation of success in such a substitution" because "both
references teach drug conjugated polypeptides" that are "used for the same
purpose (conjugate drug delivery)." Id. The Examiner concluded "by
combination Xu and Bichon describe a copolymer comprising a sodium salt
of poly(glutamyl glutamine ), poly(glutamyl glutamine )paclitaxel and
poly(glycolic acid)." Id.
According to the Examiner, "the claimed invention would have been
prima facie obvious since all the claimed elements were known in the prior
art and one skilled in the art could have combined the elements as claimed
by known methods with no change in their respective functions and the
combination would have yielded predictable results to one of ordinary skill
in the art at the time of the invention." Id. at 6-7. The Examiner made the
same conclusions with respect to the combination of Bichon and Li: an
ordinary artisan would have found it obvious to combine the monomers,
would have a high expectation in succeeding in making the combination,
and would have predictably achieved a sodium salt of poly(glutamyl
glutamine ), poly(glutamyl glutamine )paclitaxel and poly(glycolic acid) from
the combination using methods known to ordinary artisans at the time of the
invention. Non Final Rej. 8-9. The Examiner found this rationale extended
to dependent Claim 2, which claims that the polymer conjugate further
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Application 11/566, 141
comprises a recurring unit of the formula III, shown above. The Examiner
found the conjugate of Formula III is similar in chemical structure and
function to the conjugates of Formula I and II and therefore it would have
been obvious to one of skill in the art "to combine the monomers to make
such a copolymer [because] the monomers are similar in structure (peptides)
and are used for the same purpose (conjugate drug delivery)." Ans. 11.
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
prim a facie case of unpatentability ....
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
We select claim 1 as representative of the claims subject to this
ground of rejection. 37 C.F.R. § 41.37(c)(iv). Appellants' arguments do not
persuade us that a preponderance of the evidence fails to support the
Examiner's prima facie case as to claim 1.
Appellants, relying largely on the Declaration of Sang Van under
37 C.F.R. § 1.132 ("Van Deel."), argue that one of skill in the art at the time
of the invention would not have had a reasonable expectation of success in
modifying the polyaminoacids of Bichon by combining with Xu and/or Li to
arrive at the active polymer conjugates of Claim 1. App. Br. 12; Van Deel.
i-f 23. Appellants argue that Bichon' s disclosure relates to a "family of
polyaminoacid drug conjugates, not just to those based on [poly(glutamyl)
glutamine] alone" and "does not describe any working example of a polymer
drug conjugate that was actually made or whether such a polymer drug
conjugate was biologically active or inactive." App. Br. 11-12. Appellants
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Application 11/566, 141
agree with the Examiner that "'those skilled in the art would recognize that
Bichon considers polyaminoacid drug conjugates, including Bichon's
Polymer, 6 PGA and PAA drug conjugates, to be a class of
pharmacologically active polymers with generally similar properties"' but
states that "Bichon's Polymer is structurally more complex than PGA and
PAA ... and thus would expect the degradation pathways for Bichon' s
Polymer to be more complex than those of PGA and PAA." App. Br. 12;
Van Deel. i-fi-f 10-13.
Appellants agree with the Examiner that there are similarities between
the manner in which the paclitaxel drug is attached to polyaminoacids of Li
and Xu and the manner in which the drug "M" is attached to Bichon's
Polymer, but argue that those similarities do not extend to the biological
activity of the polyaminoacid drug conjugate. App. Br. 12-13; Van Deel.,
i-fi-f 14--18. Specifically, Appellants argue that Li discloses data showing a
difference in paclitaxel activity on tumors depending on the polyaminoacid
conjugate: "'poly( d-glutamic acid)-paclitaxel was as effective as poly(l-
glutamic acid)-paclitaxel. However, paclitaxel conjugated with poly(l-
aspartic acid) was completely inactive against OCA-1 tumor."' App. Br.
12-13; Van Deel. i-fi-f 16-17. Accordingly, Appellants argue that "'[b]ased
on Li, those skilled in the art would understand that relatively small
differences in the side chain of a polyaminoacid drug conjugate can render
the polyaminoacid drug conjugate inactive."' App. Br. 13; Van Deel. i-f 17.
6 Appellants refer to the polyaminoacid disclosed in Bichon where n is 2, m
is 0, and pis 2 as poly(glutamyl glutamine) ("PGGA") or "Bichon's
Polymer." See, e.g., Ans. 10.
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Application 11/566, 141
Appellants argue Dr. Van's review of the data in Xu led to a similar
conclusion: "relatively small differences in the side chain of polyaminoacid
drug conjugates can have a relatively large effect on the biological activity
of the polyaminoacid drug conjugate." App. Br. 13; Van Deel. i-f 18.
Appellants conclude various aspects of the disclosure of Bichon "are
speculative, incomplete and/or inaccurate" and therefore
one skilled in the art would have good reason to doubt the
mechanisms proposed by Bichon [] for releasing an active form
of a drug from Bichon's Polymer, particularly in view of the
greater complexity of the degradation pathways for Bichon's
Polymer as compared to PGA and PAA[], because Bichon's
proposed mechanisms fail to adequately explain the data
disclosed in in [sic] Li and Xu.
App. Br. 13; Van Deel., passim. Instead, Appellants argue that "any prima
facie case of obviousness that may have existed at the time of Bichon (issued
in 1990) had been nullified by the time of the invention in viev,r of the data
of Li (issued 2002) and/or Xu (published 2004)." App. Br. 16; Van Deel.
,-r,-r 19-23.
Appellants do not persuade us that the Examiner erred in finding that
the combination of Bichon and Li or of Bichon and Xu would have
prompted an ordinary artisan to prepare polymer conjugate of claim 1.
Bichon discloses biodegradable polypeptide derivatives of polyaspartic acid
and glutamic acid (formulas I and II claimed by Appellants). Bichon 12:45-
14:49. Bichon discloses "that the polymers have excellent solubility and
provide good control of degradation." Non-Final Rej. (citing Bichon 1: 12-
2: 12; 3:62--4:66). Bichon teaches the preparation of the polypeptide with a
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Application 11/566, 141
minimum monomer length that overlaps the molecular weight range claimed
by Appellants. Id.
Bichon teaches that anticancer agents or other drugs can be covalently
bound to such polymers for treatment of diseases such as cancer, and
specifically discloses polyglutamic acid (PGG) - as claimed by Appellants -
where m in the formula below is selected to be 0 and n = 2:
. ~
-{mi-CK~\,- . .. . ~-'M ~
.
. j
""'"·\ . 't.t;., .. ~ :jt;I_.....:;:.."' ~ .. >. ~---.......--------~···'"'"'""'~~· ~~~---"'L""i= ~ "'r' :~~~~if'l.:~ ~~ · ~~R"r'm~~~~~~m.~~{~11~---~~"G
·~ ..
Id. at 10:37-62.
1
~
At oral argument, counsel for Appellants argued that the disclosure of
Bichon focused on methods of drug delivery and the products released as the
polymer compounds hydrolyzed, rather than the suitability of the polymer
itself as a method of delivery of hydrophobic drugs. We find Bichon
discloses the biodegradable synthesis of a "non-toxic, hydrosoluble,
biodegradable polypeptide which can be used ... for various therapeutic
applications, namely to be used as a drug carrier substrate." Id. at 1 :5-8.
Bichon's disclosure claims an invention having "[e]xcellent solubility in
most current harmless solvents suitable for drugs, and even in water" id. at
1 :65--66. Counsel conceded at oral argument that Bichon does not teach or
disclose that the PGGA polymer is insoluble in water.
Xu teaches use of polypeptides containing glutamic acid and aspartic
acid "conjugated to drugs in order to improve the solubility of the drugs
and/or their therapeutic efficacy in vivo." Xu Abstract. Xu discloses "the
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Application 11/566, 141
present invention relates to the novel use of a poly( di-peptide) peptide
covalently bound to a drug to act as a drug carrier, particularly for poorly
water soluble drugs." Id. i-f 3. Xu discloses the conjugation of paclitaxel to a
poly(glutamic acid/aspartic acid) polypeptide (formula III claimed by
Appellants) for the treatment of cancer:
. ft ft ft ft '•
(--------·· NH-CH-C-NH-CH-C-NH-CH-C-NH-qH-C -·-)
t I I ! 1 ,
i CH? Ct# CH2 Cfi2 \
<' I ! ~ ! > + PacNtaxel
\) yfi2 C00/-1 )~H2 COOH (
1
, COON COOJI ) n
Po!y(g!utamic/aspartic acid.)
Id. at Fig. 2A.
Xu teaches that "the polypeptide drug carrier moiety comprises ...
more preferably from about 60 to about 80 percent, by weight, glutamic
acid." Id. ,-r 3 1.
Li teaches "water soluble compositions of paclitaxel and docetaxel
formed by conjugating the paclitaxel or docetaxel to a water soluble polymer
such as poly-glutamic acid, poly-aspartic acid or poly-lysine." Li Abstract.
Li discloses and claims a method of treating cancer comprising
administering an effective amount of a composition of paclitaxel conjugated
to a water soluble polyamino acid with a molecular weight of at least about
5,000 Daltons in a solution. Id. at 39:43-52. Li discloses PGGA conjugated
to paclitaxel in Figure 2:
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Application 11/566, 141
.l'Ol,YMlm {~Ol'WJGATE. \VlTH PLl.inAl .. JT\' OF l)fHJGS
Examp1~c:;: "J')Gl\ ,{l.,a<:~Jt;:.x.:3'1 )~·c3mpt\.Rhe·dni Pt}GA,~'pacJitaxeJ}·
<.omnptotl1;;.~.in. PCiA· 1\mclit\iCiA.-(JY.1-::lttai.:el)·
doxornbidn, l:'GA·(pacfita.--;clH:ca:i.1ptotlw.::in)·doxombi~in,
The manner in which paclitaxel is attached to polyaminoacids of Li and Xu
and the manner in which the drug "M" is attached to the polymer disclosed
in Bichon are similar, as Appellants concede. Van Deel. i-f 14.
Thus, Bichon and Xu advised an ordinary artisan that biodegradable
polypeptide derivatives of polyaspartic acid and glutamic acid, such as
PGGA, could be covalently linked to paclitaxel to improve its solubility and
provide a method of in vivo delivery. Likewise, the combination of Bichon
and Li advised an ordinary artisan that biodegradable polypeptide
derivatives of polyaspartic acid and glutamic acid, such as PGGA, could be
conjugated to paclitaxel and used to treat cancer in effective amounts. Both
Xu and Li teach specific amounts of the compositions that overlap with the
amounts claimed by Appellants. Accordingly, given these teachings, we
agree with the Examiner that an ordinary artisan would have been prompted
to combine the teachings of Bichon and Xu or Bichon and Li to create the
claimed polypeptide compositions.
It might be true, as Appellants argue, that the degradation pathways
for Bichon's Polymer are more complex than those of PGA and PAA;
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Application 11/566, 141
however, this distinction is unimportant as Appellants claim the composition
of PGGA and paclitaxel. Moreover, Appellants provide no specific
persuasive evidence that the complexity of the degradation pathway would
deter the skilled artisan from making the claimed composition.
As to the data disclosed in Xu and Li "regarding members of the
family of polyaminoacid drug conjugates indicating those members are not
suitable for drug delivery" (Reply Br. 4), we find the data do not dissuade a
skilled artisan from pursuing the combination of a polyaminoacid and
paclitaxel. "Under the proper legal standard, a reference will teach away
when it suggests that the developments flowing from its disclosures are
unlikely to produce the objective of the applicant's invention. A statement
that a particular combination is not a preferred embodiment does not teach
away absent clear discouragement of that combination." Syntex (U.S.A.)
LLC v. Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005) (citations
omitted). We find both disclosures encourage the skilled artisan to make the
claimed composition because Li disclosed that certain polyaminoacid drug
conjugates are not effective against ovarian cancer, but concluded that
poly( d-glutamic acid)-paclitaxel and poly(l-glutamic acid)-paclitaxel were
effective (Li at 33 :28-31) and Xu disclosed that paclitaxel conjugated to
polyglytamic [sic polyglutamic] acid/aspartic acid was more effective than
paclitaxel alone, despite that not all combinations of polypeptide and
paclitaxel were effective. Xu i-fi-f 159-160.
We agree with Appellants that none of the cited references contain a
"working example of a polymer drug conjugate that was actually made or
[disclose] whether such a polymer drug conjugate was biologically active or
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Application 11/566, 141
inactive." App. Br. 12; Van Deel. i-f 23. Given Bichon's disclosure of
PGGA, its suggestion to conjugate an anticancer drug for cancer treatment,
and the success disclosed in both Xu and Li using paclitaxel conjugated to
soluble polypeptides as discussed above, we are not persuaded that Bichon's
lack of a working example would have failed to prompt an ordinary artisan
to attempt to conjugate paclitaxel to PGGA to create the composition of
claim 1. Moreover, "[ o ]bviousness does not require absolute predictability
of success .... For obviousness under§ 103, all that is required is a
reasonable expectation of success." In re 0 'Farrell, 853 F.2d 894, 903---04
(Fed. Cir. 1988).
With regard to Appellants' argument that the claimed conjugates are
more soluble over a broader pH range than a comparable tested polyglutamic
acid polymer, we find the disclosed increase in solubility over a limited
range of pH is not sufficient to overcome the very strong prima facie case
presented by the Examiner. "Although secondary considerations must be
taken into account, they do not necessarily control the obviousness
conclusion." Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1372 (Fed. Cir.
2007) (citing Newell Cos., Inc. v. Kenney Mfg. Co., 864 F.2d 757, 768 (Fed.
Cir. 1988) and holding "[h ]ere, the record establishes such a strong case of
obviousness that Pfizer's alleged unexpectedly superior results are
ultimately insufficient."). Moreover, the minor increase shown is not
persuasive in rebutting obviousness because it is a "difference in degree" of
a known and expected property and not a "difference in kind" (i.e., a new
property dissimilar to the known property) Bristol-Myers Squibb Co. v. Teva
Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014); see also In re
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Application 11/566, 141
Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005) (finding a "32--43% increase
in stress-rupture life, however, does not represent a 'difference in kind' that
is required to show unexpected results." (citing In re Huang, 100 F.3d 135,
139 (Fed. Cir. 1996); and In re Merck, 800 F.2d 1091, 1099 (Fed. Cir. 1986)
(finding evidence that the new drug was a more potent sedative and stronger
anticholinergic effect than the prior art was insufficient to outweigh the
evidence of obviousness).
Appellants' argument that none of the cited references
provide any indication that the amount of paclitaxel and number
of recurring units of formula (I) and formula (II) can be selected
to advantageously control the solubility of the resulting
polymer conjugate to provide a polymer conjugate that is
soluble over a broader pH range than that of a comparable
tested polyglutamic acid conjugate solution
(App. Br. 18-19) is not persuasive as the Examiner's rejection is based on
the combined teachings of Bichon and Xu or Bichon and Li (see Final
Action 3---6). We agree with the Examiner because nonobviousness cannot
be established by attacking the references individually when the rejection is
predicated upon a combination of prior art disclosures. Merck, 800 F .2d at
1097; see also In re Keller, 642 F.2d413, 426 (CCPA 1981) (finding "one
cannot show nonobviousness by attacking references individually where, as
here, the rejections are based on combinations of references" (citations
omitted)). Thus, whether Bichon, Xu or Li individually fails to teach the
claimed composition is not dispositive to the sufficiency of the rationale
underlying the rejection. As stated by the Examiner, Bichon discloses the
PGGA polypeptide conjugate and suggests coupling to an anticancer drug.
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Final Action 3. The Examiner sufficiently establishes that an ordinary
artisan reading Bichon and Xu or Bichon and Li would have reasonably
expected that the paclitaxel anti-cancer compound taught in Xu and Li
would be useful when conjugated to the polypeptide disclosed in Bichon.
Final Action 3-6.
With regard to Appellants' arguments regarding claim 2, we find the
Examiner has a better position. Xu discloses the conjugation of paclitaxel to
a poly(glutamic acid/aspartic acid) (Appellants' formula III), therefore the
use of formula III to create a soluble anti-cancer conjugate is not unique.
Given that a polymer is by definition a string of repeated similar units, we
agree with the Examiner that one of skill in the art would recognize that the
various similar polypeptide units disclosed by Bichon, Xu and Li are
suitable for use as described in their respective disclosures and could be
substituted for one another by the ordinary artisan without changing the
solubility of the resulting conjugate and without undue experimentation.
Absent compelling evidence to the contrary, the alteration is therefore
obvious as a substitution of one element for another with a predictable result.
See KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007), citing United
States v. Adams, 383 U.S. 39, 50-51 (1966) ("[W]hen a patent claims a
structure already known in the prior art that is altered by the mere
substitution of one element for another known in the field, the combination
must do more than yield a predictable result.").
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Appeal2014-008366
Application 11/566, 141
NONSTATUTORY OBVIOUSNESS-TYPE DOUBLE PATENTING
Rejection as unpatentable over Claims 1-32 of App. No. 121019,612.
Patent application number 12/019,612, which formed the basis for this
rejection, was abandoned on October 28, 2014. Notice of Abandonment.
Accordingly, we do not reach the Examiner's rejection of nonstatutory
obviousness-type double patenting because it is rendered moot by the
abandonment.
Rejection as unpatentable over Claims 1-20 of App. No. 121117, 678.
Patent application number 12/117,678, which formed the basis for this
rejection, was abandoned on October 28, 2014. Notice of Abandonment.
Accordingly, we do not reach the Examiner's rejection of nonstatutory
obviousness-type double patenting because it is rendered moot by the
abandonment.
Rejection as unpatentable over Claims 1-19 of App. No. 121117,601, now
U.S. Patent. 8,197,828.
The Examiner has rejected claims 1, 2, 9, 10, 16-18, 20-22, 25-37,
42, 43, and 48-55 as unpatentable for nonstatutory obviousness-type double
patenting over claims 1-19 of Application No. 12/117,601, now U.S. Patent.
8,197,828.
In their Appeal Brief, Appellants declined to raise arguments against
this rejection and indicated a terminal disclaimer would be filed to obviate
the rejection. App. Br. 21. At oral argument, counsel for Appellants asked
to withdraw the request to have the issue remanded to the Examiner, and
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Appeal2014-008366
Application 11/566, 141
stated that the applicable test to this issue is the two-way test for double
patenting pursuant to MPEP 804 given that the application leading to the
'828 patent was filed after the claims at issue. We acknowledge Appellants'
technical statement made at oral argument; however, because Appellants
have not advanced any substantive argument for our review, we summarily
affirm the rejection.
SUMMARY
For the reasons discussed, we affirm the Examiner's rejection of
claims 1, 2, 9, 10, 16-18, 20-22, 25-37, 42, 43, and 48-55 as unpatentable
for obviousness under 35 U.S.C. § 103(a) over Bichon and Xu, and Bichon
and Li. Claims 9, 10, 16-18, 20-22, 25-37, 42, 43, and 48-55 have not
been argued separately and therefore fall with claims 1 and 2.
We summarily affirm the Examiner's rejection on the basis of
nonstatutory obviousness-type double patenting of claims 1, 2, 9, 10, 16-18,
20-22, 25-37, 42, 43, and 48-55 as unpatentable over claims 1-19 of
Application No. 12/117,601, now U.S. Patent. 8, 197,828.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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