Ex Parte Thorpe et al

Board of Patent Appeals and Interferences

Sep 16, 2010

10642059 (B.P.A.I. Sep. 16, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/642,059 08/15/2003 Philip E. Thorpe 4001.003100/UTSD:0968
US
2768
52101 7590 09/17/2010
PEREGRINE PHARMACEUTICALS, INC.
5353 WEST ALABAMA
SUITE 306
HOUSTON, TX 77056
EXAMINER
FETTEROLF, BRANDON J
ART UNIT PAPER NUMBER
1628
MAIL DATE DELIVERY MODE
09/17/2010 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte PHILIP E. THORPE and JIN HE
__________

Appeal 2009-014041
Application 10/642,059
Technology Center 1600
__________

Before ERIC GRIMES, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL1,2
This is an appeal under 35 U.S.C. § 134 involving claims to a
substantially cell impermeant duramycin derivatives. The Examiner rejected
the claims as lacking written description and for obviousness. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.

1 The two-month time period for filing an appeal or commencing a
civil action, as recited in 37 C.F.R. § 1.304, or for filing a request
for rehearing, as recited in 37 C.F.R. § 41.52, begins to run from
the “MAIL DATE” (paper delivery mode) or the
“NOTIFICATION DATE” (electronic delivery mode) shown on
the PTOL-90A cover letter attached to this decision.
2 Oral Hearing held September 14, 2010.
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Statement of the Case
The invention “provides a number of preferred antibody,
immunoconjugate and duramycin-based compositions that bind and inhibit
aminophospholipids and anionic phospholipids for use in the treatment of
cancer, viral infections and related diseases” (Spec. 1, ll. 13-15). Claims 1-
15, 17, 19, 21, 22, 24, and 26-32 are on appeal. The claims are separately
argued and found in Appellants’ claim appendix (App. Br. 31-35).
The issues
A. The Examiner rejected claims 1-15, 17, 19, 21-22, 24, and 26-32
under 35 U.S.C. § 112, first paragraph as failing to comply with the written
description requirement (Ans. 3-7).
B. The Examiner rejected claims 1-5 under 35 U.S.C. § 103(a) as
obvious over Molina y Vedia3 and Gaertner4 (Ans. 7-9).
A. 35 U.S.C. § 112, first paragraph, Written Description
The Examiner finds that the claims are drawn to a
genus of compounds referred to as a cell impermeant group,
wherein the cell impermeant group is selected from the
following: 1) a genus of compounds that have a positive
charge at physiological pH; 2) a genus of compounds that
has a negative charge at physiological pH; 3) a genus of
compounds having a sulfate, sulfonate, phosphate, carboxyl,
phenolic, quaternary ammonium ion or an amine group; 4) a
genus of sugar, oligo-polysaccharide, amino acid, peptide,
polypeptide or a polyalcohol group; 5) a genus of proteins;
6) a genus of inert carrier proteins; 7) a genus of
immunoglobulin carrier proteins; 8) an IgG carrier protein;

3 Molina y Vedia et al., US 5,849,706, issued Dec. 15, 1998.
4 Gaertner et al., Site-Specific Attachment of Functionalized
Poly(ethylene glycol) to the Amino Terminus of Proteins, 7
BIOCONJUGATE CHEMISTRY 38-44 (1996).
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and 9) a targeting agent, wherein the targeting agent may be
a genus of proteins that binds to a component of a tumor
cell, tumor vasculature or tumor stroma. Therefore, the
claims encompass a genus of molecules defined solely by its
principal biological property, which is simply a wish to
know the identity of any material with that biological
property.

(Ans. 4)
Appellants contend that the
specification describes a number of different species of cell
impermeant groups and provides working examples of
substantially cell impermeant duramycin derivatives
comprising a diverse collection of cell impermeant groups,
which range from large to small, and include biological and
chemical entities. Appellants have therefore described and
exemplified a diverse and sufficient number of species of
substantially cell impermeant duramycin derivatives to
provide adequate written description of the genus of
substantially cell impermeant duramycin derivatives.

(App. Br. 22).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that the claims fail to comply with the
written description requirement?
Findings of Fact
1. The Specification teaches that the “generation of a
‘substantially cell impermeant’ . . . duramycin is preferably achieved by
attaching the . . . duramycin to at least a first cell impermeant group” (Spec.
7, ll. 10-12).
2. The Specification teaches that “[s]ubstantially cell impermeant
duramycins may also be operatively attached to a sugar, oligo- or
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polysaccharide, amino acid, peptide, polypeptide, protein or a polyalcohol
group.” (Spec. 27, ll. 28-29).
3. The Specification teaches “cell impermeant duramycins are
those operatively attached to a carrier protein or ‘an inert carrier protein’,
such as neutravidin, streptavidin, albumin or an immunoglobulin carrier
protein” (Spec. 27, ll. 30-32).
4. The Specification teaches that
preferred PE[phosphatidylethanolamine]-binding peptide
constructs and derivatives are those based upon the peptide
termed duramycin. Three general categories of PE-binding
peptide and duramycin derivatives are provided by the
invention, two of which use the PE-binding peptide or
duramycin as the targeting portion of the construction, and
the other uses the duramycin or like agent mainly as the
effector portion of the construction.

(Spec. 203, ll. 7-11).
5. The Specification teaches that the “terms ‘cell impermeant
group’ and ‘cell impermeant PE-binding peptide’, as used herein, are
relative rather than absolute, and refer to modified PE-binding peptides,
preferably duramycin, in which the ability to form clusters and permeate
cells has been significantly, and preferably substantially, reduced” (Spec.
204, ll. 2-5).
Principles of Law
“[T]he determination of what is needed to support generic claims to
biological subject matter depends on a variety of factors, such as the existing
knowledge in the particular field, the extent and content of the prior art, the
maturity of the science or technology, the predictability of the aspect at
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issue, and other considerations appropriate to the subject matter.” Capon v.
Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005).
“[A]pplicants have some flexibility in the ‘mode selected for
compliance’ with the written description requirement,” but a specification
must “set forth enough detail to allow a person of ordinary skill in the art …
to recognize that the inventor invented what is claimed.” University of
Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 928 (Fed. Cir. 2004).
Analysis
The Examiner, relying on Rochester, finds that the “specification
provides neither a representative number of cell impermeant groups that
encompass the genus and subgenus’s [sic] nor does it provide a description
of structural features that are common to the genus and subgenus” (Ans. 6).
We think the instant situation is very different than Rochester, where
the claims were drawn to unidentified, unknown inhibitor compounds, with
no working examples. As the Examiner recognizes, Appellants’
Specification provides multiple different cell impermeant groups, including
biotin, immunoglobulins and charged groups as shown in Figures 13A
through 13O (see Ans. 5). Further, it is also clear that Appellants’ invention
is not intended to be the concept of cell impermeant groups, nor any of the
specific cell impermeant groups, but rather is intended to relate to their
attachment to duramycin.
The instant situation is much closer to that in Capon, where the prior
art provides the underlying information regarding the members of the genus.
As in Capon, there is no inventive contribution by Appellants to provide
unknown cell impermeant groups, but rather the asserted invention is a novel
attachment of these groups to duramycin.
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Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the claims fail to comply with the written description requirement.
B. 35 U.S.C. § 103(a) over Molina y Vedia and Gaertner
The Examiner finds that the ordinary artisan would have reasonably
expected that by “attaching the duramycin peptide as taught by Molina y
Vedia et al. to polyethylene glycol in view of Gaertner et al., one would
achieve a duramycin PEG conjugate for the treatment of tuberculosis,
wherein the conjugate shows an increase in circulatory half-life, reduction in
antigenicity and immunogenicity” (Ans. 8-9).
Appellants contend that “[t]here is no teaching, suggestion or
motivation in Molina to modify a lantibiotic such as duramycin in any way”
(App. Br. 26). Appellants further contend that “Gaertner does not teach or
suggest covalently attaching a polyalcohol to a lantibiotic or a duramycin
peptide” (App. Br. 26).
Appellants contend that “[g]iven the toxicity of duramycin, one of
ordinary skill in the art would not have been motivated to increase the
circulation of duramycin in vivo, either by covalent attachment of a
polyalcohol or mPEG, or by any other method” (App. Br. 27). Appellants
contend that “the data in Molina show that duramycin is active in the lung
for at least a week after administration. Accordingly, given the long
duration of drug action of duramycin, Molina teaches away from the need to
modify duramycin to prolong its circulatory life time in vivo” (App. Br. 28).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Molina y Vedia and Gaertner render
obvious a duramycin peptide attached to PEG?
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Findings of Fact
6. The Specification teaches that “PE-binding peptides, preferably
duramycin, can be rendered cell impermeant by attachment to an inert, cell
impermeant carrier. . . . Non-protein carriers can also be used, such as
natural or synthetic polymers including polysaccharides and PEG” (Spec.
208, ll. 1-11).
7. Molina y Vedia teaches “administering to the subject a
lantibiotic such as duramycin or a pharmaceutically acceptable salt thereof
in an amount effect to combat M. tuberculosis infections” (Molina y Vedia,
col. 3, ll. 1-4).
8. Molina y Vedia teaches that, in one embodiment, “duramycin is
administered by an intravenous bolus or by infusion, most preferably by
infusion, in a dose range of from 70 mg/day to 2.5 g/day, and more
preferably in a dose range of from 150 mg/day to 2 g/day” (Molina y Vedia,
col. 8, ll. 42-46).
9. Molina y Vedia teaches that “[a]fter duramycin was
administered the amount of airway fluid received did not return to baseline
during the 30 minute measurement period. . . . In an attempt to deal with this
unexpectedly long duration of drug action, the 160 minute Protocol 2 was
developed, which includes separating the administration of drug and vehicle
by one week” (Molina y Vedia, col. 13, ll. 8-18).
10. Gaertner teaches that “[c]ovalent attachment of
monomethoxypoly(ethylene glycol) [mPEG] to therapeutic proteins
prolongs their circulatory life time in vivo, reduces their antigenicity and
immunogenicity, and improves their resistance to proteolysis” (Gaertner 38,
col. 1).
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11. Gaertner teaches that it “is clear from the results presented
herein that by increasing the polymer mass or its molecular volume, either
by enhancing its length or by adding multiple copies of the polymer at one
site, one can increase the circulating half-life without marked loss of
functionality” (Gaertner 43, col. 2).
Principles of Law
The Supreme Court has 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., 550 U.S. 398, 418 (2007). As noted by the Court in
KSR, “[a] person of ordinary skill is also a person of ordinary creativity, not
an automaton.” 550 U.S. at 421. “The combination of familiar elements
according to known methods is likely to be obvious when it does no more
than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398,
416 (2007).
Analysis
Molina y Vedia teaches “administering to the subject a lantibiotic
such as duramycin or a pharmaceutically acceptable salt thereof in an
amount effect to combat M. tuberculosis infections” (Molina y Vedia, col. 3,
ll. 1-4; FF 7). Molina y Vedia teaches that “duramycin is administered by an
intravenous bolus or by infusion, most preferably by infusion, in a dose
range of from 70 mg/day to 2.5 g/day, and more preferably in a dose range
of from 150 mg/day to 2 g/day” (Molina y Vedia, col. 8, ll. 42-46; FF 8).
Gaertner teaches that “[c]ovalent attachment of
monomethoxypoly(ethylene glycol) [mPEG] to therapeutic proteins
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prolongs their circulatory life time in vivo, reduces their antigenicity and
immunogenicity, and improves their resistance to proteolysis” (Gaertner 38,
col. 1; FF 10).
Applying the KSR standard of obviousness to the findings of fact, we
conclude that the person of ordinary creativity would have predictably
modified the duramycin treatment of M. tuberculosis infections of Molina y
Vedia to incorporate covalently attached mPEG in order to prolong the
circulatory life time of duramycin as well as to reduce antigenicity,
immunogenicity and improve proteolysis resistance (FF 10-11). Such a
combination is merely a “predictable use of prior art elements according to
their established functions.” KSR, 550 U.S. at 417.
Appellants contend that “[t]here is no teaching, suggestion or
motivation in Molina to modify a lantibiotic such as duramycin in any way”
(App. Br. 26). Appellants further contend that “Gaertner does not teach or
suggest covalently attaching a polyalcohol to a lantibiotic or a duramycin
peptide” (App. Br. 26).
We are not persuaded. Gaertner provides several specific reasons to
attach mPEG, acknowledged by the Specification to be a cell impermeant
group, to circulating drugs and Molina y Vedia teaches treatment of
tuberculosis with duramycin administered by infusion into the circulation of
the patient (FF 6-11).
Appellants contend that “[g]iven the toxicity of duramycin, one of
ordinary skill in the art would not have been motivated to increase the
circulation of duramycin in vivo, either by covalent attachment of a
polyalcohol or mPEG, or by any other method” (App. Br. 27). Appellants
contend that “the data in Molina show that duramycin is active in the lung
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for at least a week after administration. Accordingly, given the long duration
of drug action of duramycin, Molina teaches away from the need to modify
duramycin to prolong its circulatory life time in vivo” (App. Br. 28).
While Molina y Vedia expressly teaches administration of duramycin
by infusion (FF 8), Appellants provide no evidence of duramycin’s toxicity
or that the ordinary artisan would not have been motivated to administer
duramycin by infusion as taught by Molina y Vedia. See In re Pearson, 494
F.2d 1399, 1405 (CCPA 1974) (“Attorney’s argument in a brief cannot take
the place of evidence.”).
Appellants also contend that “the Gaertner methodology is not
capable of attaching mPEG to duramycin” (Reply Br. 11). However,
Gaertner teaches modes of attachment other than by amino terminus,
including the use of reactive functional groups (see Gaertner 38, col. 1).
Appellants provide no evidence that the ordinary artisan would not have
been able to attach mPEG to duramycin following the teachings of Gaertner.
Pearson, 494 F.2d at 1405.
No arguments or evidence of any secondary considerations are found
in Appellants’ Appeal Brief. See Ex parte Borden, 93 U.S.P.Q.2d 1473
(BPAI 2010) (informative) (new arguments not permitted in Reply Brief
without showing of good cause).

Conclusion of Law
The evidence of record supports the Examiner’s conclusion that
Molina y Vedia and Gaertner render obvious a duramycin peptide attached
to PEG.
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SUMMARY
In summary, we reverse the rejection of claims 1-15, 17, 19, 21-22,
24, and 26-32 under 35 U.S.C. § 112, first paragraph as failing to comply
with the written description requirement.
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
obvious over Molina y Vedia and Gaertner. Pursuant to 37 C.F.R.
§ 41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 2-5, as these
claims were not argued separately
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006).

AFFIRMED-IN-PART

lp

PEREGRINE PHARMACEUTICALS, INC.
5353 WEST ALABAMA
SUITE 306
HOUSTON TX 77056