Ex Parte Allen et al

Board of Patent Appeals and Interferences

Feb 4, 2009

11049848 (B.P.A.I. Feb. 4, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte THERESA M. ALLEN, PAUL USTER, FRANCIS J. MARTIN,
and SAMUEL ZALIPSKY
__________

Appeal 2008-5030
Application 11/049,848
Technology Center 1600
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Decided: February 4, 2009
__________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and MELANIE
L. McCOLLUM, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to targeting
conjugates. The Examiner has rejected the claims as anticipated or obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Claims 1-26 are pending and on appeal. The claims subject to each
rejection have not been argued separately and therefore stand or fall
Appeal 2008-5030
Application 11/049,848

together. 37 C.F.R. § 41.37(c)(1)(vii). We will focus on claim 16, the
broadest claim on appeal, which reads as follows:
16. A targeting conjugate consisting essentially of (i) a lipid having
a polar head group and a hydrophobic tail, (ii) a hydrophilic polymer having
a proximal end and a distal end, said polymer attached at its proximal end to
the head group of the lipid, and (iii) a targeting ligand attached to the distal
end of the polymer, said targeting conjugate in dried form.
Claims 1-5, 16, 21, 23, and 24 stand rejected under 35 U.S.C. § 102(a)
or (b) as anticipated by Lee1 (Ans. 3).
Claims 1-26 stand rejected under 35 U.S.C. § 103(a) as obvious over
Zalipsky2 in view of Lee (Ans. 3).
Claims 10, 12, 13, 15, 23, 24, and 26 stand rejected under 35 U.S.C.
§ 103(a) as obvious over Lee or Zalipsky in view of Lee, further in view of
Kilpatrick3 (Ans. 5).
Claims 8, 9, 12, 20, and 23 stand rejected under 35 U.S.C. § 103(a) as
obvious over Lee or Zalipsky in view of Lee, further in view of Margalit4
(Ans. 5).
Claims 10, 14, 21, and 25 stand rejected under 35 U.S.C. § 103(a) as
obvious over Lee or Zalipsky in view of Lee, further in view of Nagy5
(Ans. 6).

1 Robert J. Lee and Philip S. Low, Folate-mediated tumor cell targeting of
liposome-entrapped doxorubicin in vitro, 1233 BIOCHIMICA ET BIOPHYSICA
ACTA 134-144 (1995).
2 WO 94/21281, Sep. 29, 1994.
3 US 4,913,902, Apr. 3, 1990.
4 US 5,603,872, Feb. 18, 1997.
5 US 5,985,852, Nov. 16, 1999.
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Application 11/049,848

Claims 10, 11, 13, 21, 22, and 24 stand rejected under 35 U.S.C.
§ 103(a) as obvious over Lee or Zalipsky in view of Lee, further in view of
Chang6 (Ans. 6).
ANTICIPATION
The Examiner rejects claim 16 as anticipated by Lee (Ans. 3).
Appellants do not dispute that Lee discloses a targeting conjugate
containing: (i) a lipid having a polar head group and a hydrophobic tail,
(ii) a hydrophilic polymer having a proximal end and a distal end, said
polymer attached at its proximal end to the head group of the lipid, and
(iii) a targeting ligand attached to the distal end of the polymer (see App.
Br.7 4-6).
Issue
Did the Examiner err in concluding that Lee teaches a conjugate, in
dried form, consisting essentially of a lipid, a hydrophilic polymer, and a
targeting ligand?
Findings of Fact
1. Lee discloses folate-targeted liposomes prepared by
incorporating “a folate-polyethyleneglycol-distearoylphosphatidyl-
ethanolamine (folate-PEG-DSPE) construct into the lipid bilayer” (Lee,
Abstract).
2. To prepare folate-PEG-DSPE, Lee discloses that N-Succinyl-
DSPE dissolved in chloroform was reacted with dicyclohexylcarbodiimide
to activate its carboxyl group and then folate-PEG-NH2 was added. “After

6 US 6,129,916, Oct. 10, 2000.
7 Appeal Brief dated January 30, 2008.
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Application 11/049,848

overnight stirring at room temperature, the solvent was removed from the
reaction mixture, and the lipid pellet containing the folate-PEG-DSPE
conjugate was washed twice with cold acetone.” (Id. at 136.)
Principles of Law
“A claim is anticipated only if each and every element as set forth in
the claim is found, either expressly or inherently described, in a single prior
art reference.” Verdegaal Bros., Inc. v. Union Oil Co., 814 F.2d 628, 631
(Fed. Cir. 1987). “By using the term ‘consisting essentially of,’ the drafter
signals that the invention necessarily includes the listed ingredients and is
open to unlisted ingredients that do not materially affect the basic and novel
properties of the invention.” PPG Indus. Inc. v. Guardian Indus. Corp, 156
F.3d 1351, 1354 (Fed. Cir. 1998).
“[I]n an ex parte proceeding to obtain a patent, . . . the Patent Office
has the initial burden of coming forward with some sort of evidence tending
to disprove novelty.” In re Wilder, 429 F.2d 447, 450 (CCPA 1970).
“However, when the PTO shows sound basis for believing that the products
of the applicant and the prior art are the same, the applicant has the burden
of showing that they are not.” In re Spada, 911 F.2d 705, 708 (Fed. Cir.
1990).
Analysis
Lee discloses a lipid pellet containing a folate-PEG-DSPE conjugate
(Finding of Fact (FF) 2). Lee states that “the solvent was removed from the
reaction mixture” (FF 2). The Examiner finds that “the solvent is removed
from the folate-PEG-lipid complex and therefore, the presence of a dried
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Application 11/049,848

product is implicit” (Ans. 3). We agree that the Examiner has set forth a
prima facie case that Lee discloses the conjugate in dried form.
Appellants argue, however, that the “reaction mixture from which the
solvent (i.e., chloroform) is removed necessarily includes by-products from
dicyclohexylcarbodiimide, any unreacted N-succinyl-DSPE, folate-PEG-
NH2, and folate-PEG-DS[PE]. The lipid pellet contains these same
components.” (App. Br. 5.) Therefore, Appellants argue that “it is apparent
that the synthetic reaction product described by Lee . . . does not ‘consist
essentially of’ the folate-PEG-DPSE product because either other
constituents are present or the folate-PEG-DSPE product is wet with the
acetone used to remove the other constituents” (id.).
We are not persuaded. Appellants do not dispute that, before the
acetone is added, the lipid pellet is “in dried form.” They have not provided
evidence to rebut the Examiner’s reasonable inference (Ans. 3) that
chloroform removal as taught by Lee would leave the product dried.
In addition, as discussed below, Appellants have not shown that the
conjugates in this lipid pellet do not “consist essentially of” a lipid, a
hydrophilic polymer, and a targeting ligand, as claimed. In particular, the
transitional phrase “consisting essentially of” does not exclude all other
constituents. Instead, it only excludes unlisted ingredients that “materially
affect the basic and novel properties of the invention.” PPG Indus. Inc. v.
Guardian Indus. Corp, supra. Appellants have not shown that any
by-products that would be present with the conjugate in the lipid pellet
would materially affect the basic and novel properties of the conjugate.
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Furthermore, claim 16 recites that the conjugate “consist[s] essentially
of” the recited elements. Thus, the phrase “consisting essentially of” does
not exclude unlisted elements from being in the same reaction product as the
conjugate. Instead, it excludes from the conjugate itself unlisted elements
that materially affect its basic and novel properties. As a result, the phrase
does not exclude by-products, such as dicyclohexylcarbodiimide,
N-succinyl-DSPE, and folate-PEG-NH2, which may be present with, but not
part of, the conjugate.
Conclusion
We conclude that Lee teaches a conjugate, in dried form, consisting
essentially of a lipid, a hydrophilic polymer, and a targeting ligand. We
therefore affirm the rejection of claim 16 under 35 U.S.C. § 102(a) or (b).
Claims 1-5, 21, 23, and 24 fall with claim 16.
OBVIOUSNESS
The Examiner finds that Zalipsky “discloses a conjugate wherein one
end of PEG is attached to DSPE and the other end to a polypeptide,” but that
“the ligand is attached after the formation of the liposomes” (Ans. 4). The
Examiner concludes that “it would have been obvious to one of ordinary
skill the art to attach the ligand to the PEG-lipid complex with the
subsequent formation of the liposomes, with a reasonable expectation of
success, since . . . Lee . . . teach[es] that liposomes can be formed after the
attachment of the ligands” (id.). The Examiner also concludes that “it would
have been obvious to one of ordinary skill in the art to attach any ligand
including the claimed art well known ligands . . . with a reasonable
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Application 11/049,848

expectation of success” (id.). Appellants do not dispute these findings and
conclusions (see App. Br. 6).
Issue
Did the Examiner err in concluding that Zalipsky and Lee suggest a
conjugate in dried form?
Findings of Fact
3. Zalipsky discloses a polypeptide “attached to the liposome
outer surface by a short polymer chain” (Zalipsky 8: 15-18).
4. In particular, Zalipsky discloses:
The polypeptide, such as polypeptide 28, is attached to the
liposome outer surface by a spacer chain, such as chain 30. The
spacer chain is preferably a short hydrophilic chain, such as a
100-500 dalton PEG chain, which is itself coupled to the polar
head group of a lipid, such as lipid 32, in the outer layer 34 of
the liposome bilayer.
(Id. at 8: 18-24.)
Principles of Law
Under 35 U.S.C. § 103, “the scope and content of the prior art are to
be determined; differences between the prior art and the claims at issue are
to be ascertained; and the level of ordinary skill in the pertinent art resolved.
Against this background, the obviousness or nonobviousness of the subject
matter is determined.” Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
“[A]nticipation is the epitome of obviousness.” Connell v. Sears, Roebuck
& Co., 722 F.2d 1542, 1548 (Fed. Cir. 1983).
Analysis
Zalipsky discloses a conjugate containing a “polypeptide . . . attached
to the liposome outer surface by a spacer chain, . . . which is itself coupled to
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the polar head group of a lipid” (FF 4). Zalipsky also discloses that the
“spacer chain is preferably a short hydrophilic chain, such as a 100-500
dalton PEG chain” (FF 4).
The Examiner finds that “solvent removal and the preparation of dried
form of a compound or complex is within the skill of the art of highly
developed organic chemistry” (Ans. 4-5). Thus, the Examiner concludes
that a lipid-polymer-ligand conjugate in dried form would have been
obvious. We agree that the Examiner has set forth a prima facie case of
obviousness.
Appellants argue that neither Zalipsky nor Lee teaches “a lipid-
polymer-ligand conjugate in dried form” (App. Br. 6). We are not
persuaded. First, this argument does not address the Examiner’s conclusion
that a lipid-polymer-ligand conjugate in dried form would have been
obvious. Second, as discussed above, we do not agree that Lee does not
teach a lipid-polymer-ligand conjugate in dried form.
Furthermore, we have affirmed the rejection of claim 16 as anticipated
by Lee. For this additional reason, we agree that claim 16 would have been
obvious over Zalipsky and Lee. “[A]nticipation is the epitome of
obviousness.” Connell v. Sears, Roebuck & Co., supra.
Conclusion
We conclude that Zalipsky and Lee suggest a conjugate in dried form.
We therefore affirm the rejection of claim 16 under 35 U.S.C. § 103(a).
Claims 1-15 and 17-26 fall with claim 16.
Claims 8-15 and 20-26 are also rejected under 35 U.S.C. § 103(a) as
obvious over Lee or Zalipsky in view of Lee, further in view of Kilpatrick,
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Margalit, Nagy, or Chang. We have affirmed the rejection of these claims as
obvious over Zalipsky and Lee. For the same reasons, we affirm the
rejections of these claims over Zalipsky and Lee, in view of Kilpatrick,
Margalit, Nagy, or Chang.
ORDER
We affirm the rejection of claims 1-5, 16, 21, 23, and 24 under 35
U.S.C. § 102(a) or (b). We also affirm the rejections of claims 1-26 under
35 U.S.C. § 103(a).
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

Ssc:
THERESA M. ALLEN
11223 72ND STREET
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