Ex Parte Yang et al

Patent Trial and Appeal Board

Sep 7, 2016

12009421 (P.T.A.B. Sep. 7, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/009,421 01/18/2008 David J. Yang
23364 7590 09/09/2016
BACON & THOMAS, PLLC
625 SLATERS LANE
FOURTH FLOOR
ALEXANDRIA, VA 22314-1176
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.
Y ANG3613/REF/LES 4298
EXAMINER
MAIER, LEIGH C
ART UNIT PAPER NUMBER
1673
NOTIFICATION DATE DELIVERY MODE
09/09/2016 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):
MAIL@BACONTHOMAS.COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Exparte DAVID J. YANG, DONG-FANG YU,
and I-CHIEN WEI 1
Appeal2015-002230
Application 12/009,421
Technology Center 1600
Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
JOHN G. NEW, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellants state the real party-in-interest is The Board of Regents, The
University of Texas System. App. Br. 1.
Appeal2015-002230
Application 12/009,421
SUMMARY OF THE CASE
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner's Final Rejection of claims 1, 2, 7, 11, 13, 14, 16, and 17 as
unpatentable under 35 U.S.C. § 103(a) as being obvious over the
combination of Serino et al. (US 4,793,986, December 27, 1998) ("Serino"),
Sood et al. (US 2004/0175387 Al, September 9, 2004) ("Sood"), and
Thorpe (US 5,762,918, June 9, 1998) ("Thorpe").
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' invention is directed to, in one embodiment, a
polysaccharide conjugate. This conjugate has a polysaccharide and at least
one monomeric amino acid having an 0-group covalently bound to the
polysaccharide. The conjugate also has at least one metal conjugated by the
0-group of the amino acid. According to another embodiment, the
disclosure provides a method of synthesizing a polysaccharide conjugate by
covalently bonding a monomeric amino acid having an 0-group to a
polysaccharide and by conjugating a metal to the 0-group to form a
polysaccharide conjugate. According to a third embodiment, the disclosure
relates to a method of killing a cancer cell by administering to the cell an
effective amount of a polysaccharide conjugate. This conjugate has a
polysaccharide and at least one monomeric amino acid having an 0-group
covalently bound to the polysaccharide. The conjugate also has at least one
metal conjugated by the 0-group of the amino acid. Abstract.
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REPRESENTATIVE CLAIM
Claim 1 is representative and recites:
1. A polysaccharide conjugate comprising:
a chondroitin;
at least one aspartic acid; and
at least one molecule having platinum,
wherein said polysaccharide conjugate is represented by the following
formula:
App. Br. 10.
ISSUES AND ANALYSES
We agree with, and adopt, the Examiner's findings and conclusion
that the appealed claims are prim a facie obvious over the cited prior art
references. Appellants do not argue the claims separately, and therefore we
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Application 12/009,421
select claim 1 as representative. We address the arguments raised by
Appellants below.
Issue 1
Appellants argue the Examiner erred by failing to establish a prima
facie case of obviousness of the claimed subject matter over the combined
cited prior art. App. Br. 3.
Analysis
Appellants argue Serino teaches an antitumor compound comprising a
polysaccharide carrier which has been chemically activated and then linked
to platinum through a bidentate oxygen-containing ligand including an
amine group coupled to the activated polysaccharide. App. Br. 4 (citing
Serino Abstr.). However, Appellants point out, in contrast to their invention,
Serino teaches the carrier is activated, whereas Serino does not teach or
suggest directly linking the platinum complex to the carrier without an
activation step. Id. Therefore, Appellants argue, the end product of Serino
does not have the same polysaccharide structure as the presently claimed
conjugate. Id.
Appellants argue Serino teaches linking the platinum complex to the
carrier molecule directly, or indirectly through a ligand. App. Br. 5 (citing
Serino col. 2, 11. 43--46). Appellants assert the "direct" linkage embodiment
of "[platinum complex]-[ligand (aspartate)]-[polymer]" is closest to the
claimed structure of the present invention. Id. However, argue Appellants,
in contrast to their invention, Serino requires that this direct linkage be
fulfilled by an activation step. Id. Appellants point to Serino's teaching:
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Application 12/009,421
"Direct linkage of the ligand to the carrier typically involves reaction
between an appropriately functionalized ligand such as amino-malonic acid,
and a carrier, such as a dextran or inulin which has been appropriately
activated." Id. (quoting Serino col. 4, 11. 3-8) (emphasis added). Appellants
further contend that every relevant example disclosed by Serino includes an
activation step and that Serino therefore fails to teach or suggest "direct"
linking without the activation step. Id.
Appellants further assert that Serino teaches three different methods
for activating the carrier: activation with (1) sodium meta-periodate/sodium
cyanoborohydride; (2) cyanogen bromide; or (3) tresyl chloride. App. Br. 5
(citing Serino col. 4, 11. 8-13). Appellants contend that each of these
activation methods would result in a conjugate having a significantly
different structure than the presently claimed conjugate. Id.
The Examiner disagrees that Serino requires the carrier to be
activated. Ans. 4. The Examiner finds that, in addition to the passage
quoted by Appellants, Serino further teaches that "[P]latinum may be
attached to the macromolecular carrier by either reacting an intact
functionalized platinum complex with the carrier, which may or may not be
activated by one of the many procedures for the activation of such carriers
.... " Id. (quoting Serino col. 3, 11. 34--38) (emphasis added). The Examiner
finds the composition taught by Serino requires some suitable
macromolecular carrier generally for conjugation of a platinum-containing
compound. Id. The Examiner finds Serino exemplifies a particular method
of attaching the platinum complex to particular polysaccharides, and further
finds this method for these particular polysaccharides comprises an
activation step. However, the Examiner finds, Serino does not teach this
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Application 12/009,421
oxidation as a required step in the attachment of the platinum complex to
macromolecules generally. Id.
Appellants reply that the Examiner is misapprehending the full
teachings of Serino. Reply Br. 1. Appellants point to the paragraph of
Serino quoted by the Examiner, which states:
"Platinum may be attached to the macromolecular carrier by ...
either reacting an intact functionalized platinum complex with
the carrier, which may or may not be activated by one of the
many procedures for the activation of such carriers, Axen, R. et
al (1967) Nature (London) 214, 1302-4; Nilsson, K. and
Mosbach, K. (1981) Biochem. Biophys. Res. Commun. 102,
449-52, or by ... first reacting the carrier with an appropriate
ligand which can then serve to coordinate platinum in a
subsequent reaction." In either of these ways, platinum may be
attached to the carrier in a +2 or +4 oxidation state such that (i)
linkage of the ligand to the carrier is 45 covalent, (ii) the drug-
carrier conjugate remains water-soluble after the modification
procedure, and (iii) release of an "active" platinum antitumor
complex from the carrier is possible.
Id. at 1-2 (quoting Serino col. 3, 11. 32--49 (emphasis added). Appellants
interpret these passages of Serino as teaching two methods by which
platinum can be attached to the macromolecule: (1) reacting an intact
functionalized platinum complex with the carrier; or (2) first reacting the
carrier with an appropriate ligand which can then serve to coordinate
platinum in a subsequent reaction. Id. at 2. Appellants assert that method
(2) corresponds to the claimed composition, because aspartate is the "ligand"
first reacted to the carrier before coordination of the platinum complex
binding. Id.
Appellants argue that the language of the quoted paragraph of Serino
determines that it is only method 1 in which that carrier "may or may not be
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Application 12/009,421
activated." Reply Br. 2. Appellants therefore contend that a person of
ordinary skill in the art would recognize that Serino teaches two methods for
linking platinum, only one of which, the second method, is similar with the
present invention. Id. However, Appellants contend, in contrast to their
claimed invention, Serino requires an activation step in the second method,
which would result in a composition patentably distinct from those taught by
Serino. Id.
We are not persuaded by Appellants' arguments. We see no explicit
requirement in the teachings of Serino that explicitly requires that the carrier
be activated in the second "direct" method described by Appellants supra.
Serino teaches: "reacting an intact functionalized platinum complex with the
carrier, which may or may not be activated by one of the many procedures
for the activation of such carriers." Serino col. 3, 11. 3 5-3 8 (emphasis
added). Serino thus explicitly teaches that the carrier need not be activated.
The immediately subsequent portion of the same sentence of Serino (after
some external references) recites: "or by first reacting the carrier with an
appropriate ligand which can then serve to coordinate platinum in a
subsequent reaction." Id. at 11. 41--43. We interpret this language to mean
that, in the latter segment, "the carrier" (emphasis added) refers to the same
carrier recited in the former segment, i.e., the carrier "which may or may not
be activated." Appellants provide no evidence that the second method
explicitly requires that the carrier be activated, and we agree with the
Examiner that a person of ordinary skill would realize that the carrier, in
either method taught by Serino, may or may not be activated.
Nor are we persuaded by the other passages of Serino cited by
Appellants. Serino also teaches: "Direct linkage of the ligand to the carrier
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Application 12/009,421
typically involves reaction between an appropriately functionalized ligand
such as amino-malonic acid, and a carrier, such as a dextran or inulin which
has been appropriately activated." Serino col. 4, 11. 3-7. However, we again
find that the quoted passage does not specifically require the carrier be
activated, only that it may typically be. And although the activation of
carriers taught in the various examples taught by Serino may represent
exemplary or preferred embodiments, such embodiments are not the arbiters
of whether a teaching or suggestion is obvious; non-preferred embodiments
must also be considered. See Merck & Co., Inc. v. Biocraft Labs., Inc., 874
F.2d 804, 807 (Fed. Cir. 1989) ("[A]ll disclosures of the prior art, including
unpreferred embodiments, must be considered").
We consequently agree with the Examiner that a person of ordinary
skill would have realized from the teachings of Serino that, in the method of
synthesis Appellants admit constructs a molecule corresponding to their
claimed invention, that the carrier need not be activated.
Issue 2
Appellants argue that Sood neither teaches nor suggests the
limitations of claim 1 nor cures the alleged deficiencies of Serino. App. Br.
7.
Analysis
Appellants note that Stewart et al. (US 2001/0038830 Al, November
8, 2001) (now issued as US 6,692,734 B2, February 17, 2004) ("Stewart"),
is the parent application of Sood, which was published as a continuation-in-
part ("CIP") of Stewart. App. Br. 7.
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Appellants contend the inventions taught by Serino, Sood, and
disclosed by Appellants' application were all the results of attempts to
resolve the limitation of platinum-based drugs; however, each of these
results were achieved by significantly different means and provided
structurally different conjugates.
Appellants contend the key concept of the two sequential studies
described in Stewart was based on the unexpected result that an 0,0' -
amidomalonate platinum conjugate and an N,0-amidomalonate platinum
conjugate have "preferential biological activity for the treatment of cancer,
specifically an improved therapeutic index." Id. at 7-8 (citing Stewart i-f 14).
According to Appellants, the unpredictability of the art (in particular the lack
of knowledge of what specific conjugates may be applicable for improving
the efficacy and safety of platinum-based drugs), and the teachings of Sood,
would [not]2 have motivated a person of ordinary skill in the art to conjugate
a platinum-based drug by forming the conjugate with an amidomalonate. Id.
The Examiner responds that Sood, and not Stewart, formed the basis
of the Examiner's rejection. Ans. 5. The Examiner finds Sood teaches that
it is known in the art to conjugate platinum compounds to polymers such as
polysaccharides, and that chondroitin is a suitable polysaccharide for such
conjugation. Id.
Appellants reply that, because Sood is a continuation in-part of
Stewart, Sood is still restricted by the inventive concept of the patent family.
Reply Br. 3 (citing, e.g., X2Y Attenuators, LLC v. Int'! Trade Comm., 757
2 We understand Appellants to mean that a person of ordinary skill would
not have been motivated to synthesize the platinum-based conjugate, despite
Appellants' statement to the contrary. See App. Br. 8.
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Application 12/009,421
F.3d 1358 (Fed. Cir. 2014). Appellants repeat their argument that "0,0[']-
amidomalonate Pt conjugate /N,0-amidomalonate Pt conjugate" is the key
feature highlighted in the parent application of Sood and there are no other
conjugations or structures taught or suggested in Sood. Id. (citing App. Br.
7-8). Appellants argue that, although Sood is a CIP application, the
disclosure of Sood was derived from the inventive concept of the parent
application and does not include any additional conjugations or structures.
Therefore, contend Appellants, it is reasonable that those having
ordinary skill in the art, while referring to Sood, would not have looked
outside of the basic structure of "0,0[']-amidomalonate Pt conjugate /N,0-
amidomalonate Pt conjugate." Reply Br. 3. According to Appellants, a
person of ordinary skill in the art would not have combined Sood with
Serino because they are conceptually different from each other and the
alleged contribution of Sood to the combination would not have been within
the scope of the inventive concept in Sood. Id.
We are not persuaded by Appellants' arguments. The Examiner based
the rejections over the combination of Serino and Sood. Sood teaches:
Thus, the present invention provides means for selectively
preparing essentially pure amidomalonate 0,0'-Pt and N,0-Pt
chelates. It also provides the essentially pure amidomalonate
0,0'-Pt and N,0-Pt chelates prepared using the methods.
For example, without limitation, it will be recognized by those
with skill in the [ ... ] art that other polymers other than
poly(HPMA) and poly(glu) that have carboxyl, sulfonate, or
sulfate groups (including but not limited to glycosaminoglycans
such as hyaluronic acid, dermantan sulfate, heparin, chondroitin
sulfate and the like) could be coupled to Ama-diEt, directly or
through spacers such as aminoacids or polyaminoacids under
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Application 12/009,421
aqueous or nonaqueous conditions with conventional coupling
agents.
Sood i-fi-1277-78 (emphases added). We consequently agree with the
Examiner that Sood teaches conjugation of platinum compounds to polymers
such as polysaccharides, and that chondroitin is a suitable polysaccharide for
such conjugation. See Ans. 5. Nor are we persuaded by Appellants that the
fact that Sood is a continuation-in-part of Stewart is relevant to the
Examiner's conclusion of obviousness. Appellants contend that, because
Sood is a continuation in-part of Stewart, Sood is still restricted by the
inventive concept of the patent family. See Reply Br. 3. Even were we,
arguendo, to agree with this contention, it does not alter the Examiner's
analysis. Appellants do not contest the Examiner's finding that Sood is prior
art to their application. The test for obviousness is "what the combined
teachings of the references would have suggested to those of ordinary skill
in the art." Jn re Keller, 642 F.2d 413, 425 (C.C.P.ii ... 1981). l\1oreover,
obviousness dos not require that "a secondary reference may be bodily
incorporated into the structure of the primary reference; nor is it that the
claimed invention must be expressly suggested in any one or all of the
references." Id. The Examiner has relied upon Sood as teaching
conjugation of platinum compounds to polymers such as polysaccharides,
and that chondroitin is a suitable polysaccharide for such conjugation. Ans.
5. We agree with the Examiner's findings and, furthermore, we have
explained supra why we agree with the Examiner's findings with respect to
the teachings of Serino. We therefore conclude Appellants have failed to
overcome the Examiner's primafacie conclusion of obviousness.
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Issue 3
Appellants argue the Examiner erred because the unexpected results
disclosed in Appellants' Specification render the claims nonobvious. App.
Br. 8.
Analysis
Appellants argue that the particular recited conjugates of the present
invention unexpectedly demonstrate improved efficacy. App. Br. 8 (citing,
e.g., Spec. Ex. 2, 3). According to Appellants, a person of ordinary skill in
the art would not have reasonably predicted that, among numerous if not
countless possible candidate structures, the presently claimed conjugates
would be found suitable for use as improved platinum-containing anti-cancer
drugs. Id.
The Examiner responds that Appellants do not explain what is meant
by "improved." Ans. 6. The Examiner finds Example 2 of Appellants'
Specification compares the in vitro cytotoxicity of the claimed platinum
conjugate with cisplatin. Id. The Examiner finds the structure of cisplatin is
depicted in Figure 1 of Sood and is not equivalent in structure to the
platinum complex moiety of Appellants' claimed platinum conjugate. Id.
Nor, the Examiner finds, is cisplatin conjugated to any macromolecule. Id.
The Examiner finds that Serino teaches that: "[i]n general, these
macromolecular drug conjugates have proven less toxic than the monomeric
drug while being equally or more effective in killing cancer cells." Id.
(quoting Serino col. 1, 11. 56-58; see also Sood i-f 6).
The Examiner further finds Example 3 teaches an in vivo assay of the
tumor cytotoxicity of platinum-chondroitin conjugate versus chondroitin,
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per se. The Examiner concludes that it is not unexpected that a conjugate
comprising a platinum-drug has greater activity than the unconjugated
chondroitin. Ans. 6.
We are not persuaded by Appellants' arguments. Serino explicitly
teaches that it was well-known in the art that: "these macromolecular drug
conjugates have proven to be less toxic than the monomeric drug while
being equally or more effective in killing cancer cells." Serino col. I, 11. 5 6-
59. Cisplatin, as depicted in Figure 1 of Sood, is a platinum monomer that is
not conjugated to a polysaccharide.
Furthermore, chondroitin, as used in Example 3, is a polysaccharide
that contains no conjugated platinum. We are not persuaded, therefore, that
Appellants have demonstrated unexpected results in view of the teachings of
Serino and the known properties of chondroitin, that Appellants have
demonstrated that the activity of their claimed compound is "unexpected" in
view of the teachings of the closest prior art. See In re Baxter Travenol
Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) ("[W]hen unexpected results are
used as evidence of nonobviousness, the results must be shown to be
unexpected compared with the closest prior art" (emphasis added)). We
consequently affirm the Examiner's rejection of the claims.
DECISION
The Examiner's rejection of claim 1 as unpatentable under 35 U.S.C.
§ 103(a) is affirmed. Claims 2, 7, 11, 13, 14, 16, and 17 fall with claim 1.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l). See 37 C.F.R.
§ 1.136(a)(l )(iv).
AFFIRMED
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