Ex Parte Teifel et al

Patent Trial and Appeal Board

May 25, 2017

10575779 (P.T.A.B. May. 25, 2017)

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.
10/575,779 09/28/2007 Michael Teifel S219-0006US 9429
29150 7590 05/30/2017
LEE & HAYES, PLLC
601 W. RIVERSIDE AVENUE
SUITE 1400
SPOKANE, WA 99201
EXAMINER
SCHULTZ, JAMES
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
05/30/2017 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):
lhpto@leehayes.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MICHAEL TEIFEL, UWE MICHAELIS, BIRGITTA SAUER,
KERSTIN BARTELHEIM, CHRISTOPH BRUNNER, and
KURTNAUJOKS1
Appeal 2016-006546
Application 10/575,779
Technology Center 1600
Before ERIC B. GRIMES, TAWEN CHANG, and TIMOTHY G. MAJORS,
Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to a method
of treatment, which have been rejected as anticipated or obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the Real Party in Interest as SynCore Biotechnology
Co., Ltd. (Communication filed May 26, 2016.)
Appeal 2016-006546
Application 10/575,779
STATEMENT OF THE CASE
The Specification states that “administration of a cationic [positively
charged] liposomal preparation having a high content of paclitaxel as an
active ingredient selectively affects angiogenic endothelial cells in a human
patient in need thereof.” (Spec. 5:11—14.) “The present pharmaceutical
composition can be administered at a monthly dose of about 0.25 mg up to
about 100 mg.” {Id. at 6:16—17.) “The monthly dose is preferably
administered in a plurality of single dose units.” {Id. at 7:26—27.)
Claims 36, 44—51, 64—69, 72, 73, and 85—90 are on appeal. Claim 36
is illustrative and reads as follows:
Claim 36: A method of treating a human patient suffering from
a disease or condition, comprising administering to a patient in
need thereof a pharmaceutical composition comprising a cationic
liposomal preparation comprising at least one cationic lipid from
about 30 mole% to about 99.9 mole%, paclitaxel in an amount of
at least about 0.1 mole%, and a neutral and/or anionic lipid from
about 0 mole% to about 70 mole%, wherein the amount of
paclitaxel in a single dose of the pharmaceutical composition is
between 0.275 and 1.1 mg/kg body weight of the patient.
The claims stand rejected as follows:
Claims 36, 44, 45, 49-51, 67, 72, 73, and 85-87 under 35 U.S.C.
§ 102(b) as anticipated by Rahman2 (Ans. 2) and
Claims 36, 44—51, 64—69, 72, 73, and 85—90 under 35 U.S.C. § 103(a)
as obvious based on Rahman and McDonald3 (Ans. 5).
2 Rahman, US 6,146,659, issued Nov. 14, 2000.
3 McDonald et al., US 7,112,338 B2, issued Sept. 26, 2006.
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I
The Examiner has rejected claims 36, 44, 45, 49-51, 67, 72, 73, and
85—87 as anticipated by Rahman. The Examiner finds that “Rahman teaches
administering cationic liposome-encapsulated paclitaxel.” (Ans. 4.) The
Examiner also finds that Rahman teaches administering liposomal paclitaxel
at a dosage of 0.5—5.0 mg/kg body weight. (Id.) The Examiner finds that
Rahman therefore anticipates the claimed method.
Appellants argue that the only specific cationic liposomes described
by Rahman are made up of phosphatidyl choline, cholesterol, and stearyl
amine, which includes a positively charged amine but no cationic lipid, as
required by the claims. (Appeal Br. 7.) Appellants also argue that Rahman
does not disclose administering a composition comprising paclitaxel in
cationic lipids to a human patient. (Id.)
We agree with Appellants that Rahman’s disclosure does not meet the
standard required by 35 U.S.C. § 102(b). Rahman discloses administering
liposomally encapsulated taxanes, such as paclitaxel, to a patient. (Rahman
1:10—12, 2:41—45.) Rahman discloses that “the liposomes may be neutral,
negative or positive liposomes. For example, positive liposomes may be
formed from a solution containing phosphatidyl choline, cholesterol, and
stearyl amine.” (Id. at 3:43—46.) Rahman states that its
pharmaceutical composition is administered in the amount of
about 50 to 300 mg active compound/m2 of mammalian host
surface area. For a human, for example, of about 70 kg body
weight, from about 0.5 to 5.0 mg active compound per kg of body
weight is administered. Preferably, about 1.0-3.0 mg of active
compound per kg of body weight is administered.
(Id. at 4:6-12.)
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Claim 36, however, requires administering a composition
comprising a liposomal preparation comprising a cationic lipid;
Rahman only describes positive liposomes comprising a cationic
amine (stearyl amine), not a cationic lipid, let alone a cationic lipid in
a mole% of 30-99.9%, as required by claim 36. In addition, Rahman
does not disclose administering any composition comprising
paclitaxel encapsulated in cationic liposomes to a human patient. We
therefore agree with Appellants that Rahman does not disclose all of
the limitations of the rejected claims. The rejection under 35 U.S.C.
§ 102(b) is reversed.
II
The Examiner has rejected all of the claims on appeal as obvious
based on Rahman and McDonald. The Examiner finds that McDonald
discloses “the use of liposomally-delivered paclitaxel for the purpose of
treating various cancers.” (Ans. 6.) The Examiner also finds that McDonald
discloses the combination of the cationic lipid DOTAP, neutral lipid DOPC,
and paclitaxel at a ratio of 50:47:3, as recited in dependent claim 48 of the
instant application. (Id. at 6—7.) Finally, the Examiner finds that McDonald
teaches that an appropriate dose of cationic liposomally encapsulated
paclitaxel can be readily determined by a skilled artisan by starting with a
small dose and increasing it until the desired results are shown. (Id. at 7.)
The Examiner concludes that the claimed method would have been obvious
because Rahman discloses a range of dosages that overlaps the claimed
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range and McDonald teaches that cationic liposomes target tumors. (Id. at
7-8.)
We agree with the Examiner that the method of claim 36 would have
been obvious to a person of ordinary skill in the art based on Rahman and
McDonald. McDonald discloses “cationic liposome delivery of taxanes to
blood vessels” to inhibit angiogenesis. (McDonald 1:17—18, 6:14—25.)
“‘Taxanes’ include paclitaxel.” (Id. at 20:28.)
McDonald states that cationic lipids useful in its composition include
“l,2-diacyl-3-trimethylammonium-propanes, (including but not limited to,
dioleoyl (DOTAP),. . .).” (Id. at 17:66 to 18:3.) McDonald also states that
“[njeutral lipid can be incorporated into the cationic liposome formulations,
. . . including, but not limited to, a phosphatidyl ethanolamine, including, but
not limited to . . . DOPC.” (Id. at 22:25—33.) McDonald discloses that one
embodiment of its composition “comprises DOTAP:DOPC:paclitaxel in a
50:47:3 molar ratio.” (Id. at 22:51—52.)
Thus, McDonald discloses a specific embodiment of its composition
that includes each of the components recited in claim 36, in amounts that are
encompassed by the claim. McDonald also discloses that cationic liposomes
selectively associate with angiogenic endothelial cells and thus are useful for
delivering an active agent to treat such cells. (Id. at 6:14—25.) Similarly,
Rahman discloses that liposomally encapsulated paclitaxel is useful for
treating patients. (Rahman 4:42-43, 4:49-50.) Therefore, it would have
been obvious to use McDonald’s composition comprising a 50:47:3 molar
ratio of DOTAP:DOPC:paclitaxel to treat a human patient suffering from a
disease or condition, as recited in claim 36.
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McDonald also discloses that “those skilled in the art can, using the
present disclosure, readily determine appropriate dosing by first
administering extremely small amounts and incrementally increasing the
dose until the desired results are obtained.” (McDonald 24:38-42.) In
addition, Rahman suggests that, “[f]or a human, for example, of about 70 kg
body weight, from about 0.5 to 5.0 mg active compound per kg of body
weight is administered. Preferably, about 1.0-3.0 mg of active compound
per kg of body weight is administered.” (Rahman 4:8—12.)
Based on these disclosures, it would have been obvious to a skilled
artisan to select a dosage at the lower end of Rahman’s dosage ranges—such
as 0.5 or 1.0 mg/kg body weight—as the starting point for the dosage
optimization suggested by McDonald. The prior art provides a reason to do
so, because McDonald suggests beginning the optimization process “by first
administering extremely small amounts and incrementally increasing the
dose until the desired results are obtained.” (McDonald 24:38-42.)
Therefore, it would have been obvious to use the smallest amount suggested
in the references, Rahman’s 0.5 mg/kg body weight, as the starting dosage
for McDonald’s dosage optimization.
Appellants argue that “Rahman only discloses delivery of therapeutic
agents using anionic [negatively charged] liposomes” and “[t]he dose of
paclitaxel for delivery to a human patient using the anionic liposomes of
Rahman is not applicable to the delivery of paclitaxel using cationic
liposomes.” (Appeal Br. 9.) Appellants cite the Lander Declaration4 as
4 Declaration under 37 C.F.R. § 1.132 of Thomas Lander, filed July 3, 2013.
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evidence that cationic liposomes are structurally and functionally different
from anionic liposomes. {Id. at 9—10.)
This argument is unpersuasive, because Rahman states that its method
can be practiced with neutral, negatively charged, or positively charged
liposomes, and does not make any distinction in its recommended dosages
based on the type of liposomes used. (Rahman 3:43—44, 4:6—13.) Thus,
regardless of structural or functional differences, a skilled worker would
have reasonably expected the dosage ranges disclosed by Rahman to be
useful for compositions with neutral, negatively charged, or positively
charged liposomes. In addition, McDonald provides reason to use cationic
lipids to deliver paclitaxel and suggests optimizing dosages by starting with
extremely small amounts and incrementally increasing the dosage. We
agree with the Examiner that the claimed method would have been obvious
based on the combined disclosures of the references.
Appellants cite the Lander Declaration as evidence that “clinicians
would not have used cationic liposomal formulations containing low doses
of paclitaxel.” (Appeal Br. 10.) Dr. Lander declared that
the conventional method of treating patients with paclitaxel was
to administer up to the maximum tolerated dose (MTD) of
paclitaxel in an attempt to eradicate all tumor cells as quickly and
completely as possible. However, the conventional method of
administering MTD of paclitaxel caused severe side effects
because a large dose of paclitaxel was administered to the
patient.
(Lander Deck 14(a)(ii).)
Dr. Lander does not, however, cite any evidence showing the
“conventional” nature of the described treatment, and it is contrary to the
express disclosure of McDonald that those skilled in the art determine
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appropriate dosing by starting with small amounts and gradually increasing
the dosage. (McDonald 24:38-42.) McDonald also discloses that its
method “makes it possible to administer substantially smaller amounts of
any substance as compared with delivery systems which target the
surrounding tissue.” {Id. at 24:44-47.) Thus, we find that the cited
references would not have suggested starting with a high dose that was
likely to cause severe side effects.
Appellants also argue that the dosages disclosed in Rahman that are in
units of mg/m2 (milligrams per square meter of body surface area) do not
overlap the range in claim 36. (Appeal Br. 11—12.) Appellants argue that
when Rahman’s mg/m2 dosage ranges are converted to mg/kg using the
conversion factor described by Freireich,5 they result in dosages that are
outside of the claimed range. {Id. at 12—13.) Appellants cite Ex parte Darr,
Appeal No. 2011-0011436 (PTAB 2013), as supporting their position that
when the units used in a reference are obviously incorrect, a rejection based
on use of those units should be reversed. (Appeal Br. 14.)
These arguments are unpersuasive. Regarding Appellants’ argument
based on converting the dosage ranges in Rahman from mg/kg to mg/m2 and
vice versa, we agree with the Examiner (Ans. 17) that no conversion would
be necessary for a skilled worker to understand Rahman’s dosages that are
expressed in mg/kg, because they are expressly set forth in those units.
5 Freireich et al., “Quantitative Comparison of Toxicity of Anticancer
Agents in Mouse, Rat, Hamster, Dog, Monkey, and Man,” 50 Cancer
Chemother. Rep. 219—244 (1966).
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Appellants’ argument regarding Ex parte Darr is also unpersuasive.
That decision dealt with an appeal in which the evidence showed that “one
of ordinary skill in the art would immediately recognize 0.827 as inches
rather than millimeters as the unit of length for distance ‘e.’” Darr, slip
opinion at 4. Here, by contrast, the evidence does not show that a person of
ordinary skill in the art would immediately recognize Rahman’s disclosure
of certain dosage ranges in units of mg/kg to be typographical errors, or
indeed to have anything other than their plain meaning.
Finally, Appellants argue that the Examiner has not adequately
responded to the Lander Declaration. (Appeal Br. 15.) Appellants then
address the references cited by the Examiner in responding to the Lander
Declaration {id. at 15—17) and conclude that “[t]he Examiner has improperly
dismissed the declaration of Dr. Lander as providing mere opinion” {id. at
17).
This argument is also unpersuasive. We have thoroughly considered
the Lander Declaration but find that it does not provide evidence that
outweighs the evidence of obviousness provided by Rahman and McDonald.
Dr. Lander cites three references as describing clinical trials using liposome-
encapsulated paclitaxel at doses higher than those recited in claim 36.
(Lander Deck 14(a)(iii).) Dr. Lander declares that “low dosages of
paclitaxel, such as those recited in the claims of U.S. Application ’779, were
not used clinically for treatment purposes.” {Id. 14(a)(iv).)
This evidence is not persuasive of nonobviousness, because
McDonald suggests using extremely small dosages as the starting point for
dosage optimization (McDonald 24:38-42); states that cationic liposomes
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selectively associate with angiogenic endothelial cells (id. at 6:14—25.); and
discloses that using cationic liposomes to deliver paclitaxel allows
substantially smaller amounts to be used (id. at 24:44-45.) Dr. Lander does
not describe any of the cited clinical trials as using paclitaxel encapsulated in
cationic liposomes.
Dr. Lander also states that “[cjationic liposomes are structurally and
functionally different from neutral and anionic liposomes for delivery of
agents.” (Lander Decl. 14(b).) This point has been addressed above. To
reiterate, Rahman would have led a skilled artisan to expect that the same
range of dosages of liposomally encapsulated paclitaxel would be effective
regardless of the type of liposome, and McDonald suggests using small
amounts of paclitaxel in cationic liposomes for dose optimization, and
suggests that they preferentially target angiogenic epithelial cells, enabling
effective dosages with smaller amounts of paclitaxel.
Finally, Dr. Lander discusses the teachings of McDonald and Rahman
individually. (Lander Decl. 14(c), (d).) Dr. Lander concludes that “[a]
clinician would not have combined the teachings of McDonald and Rahman
and would not have applied the teachings of one reference to the other as
they are directed to delivery of active agents using structurally and
functionally different liposomes.” (Id. 14(e).)
For the reasons thoroughly discussed above, however, we conclude
that a preponderance of the evidence of record supports the Examiner’s
conclusion that the method of claim 36 would have been obvious to a person
of ordinary skill in the art based on Rahman and McDonald.
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Claims 44—51, 64—69, 72, 73, and 85—90 have not been argued
separately and therefore fall with claim 36. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We reverse the rejection of claims 36, 44, 45, 49-51, 67, 72, 73, and
85—87 under 35 U.S.C. § 102(b) as anticipated by Rahman.
We affirm the rejection of claims 36, 44—51, 64—69, 72, 73, and 85—90
under 35 U.S.C. § 103(a) based on Rahman and McDonald.
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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