Markus Rast et al.

Patent Trials and Appeals Board

Sep 26, 2019

14068074 - (D) (P.T.A.B. Sep. 26, 2019)

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.
14/068,074 10/31/2013 Markus RAST 32499U 9497
34375 7590 09/26/2019
NATH, GOLDBERG & MEYER
Joshua Goldberg
112 South West Street
Alexandria, VA 22314
EXAMINER
KOLKER, DANIEL E
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
09/26/2019 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):
USPTO@nathlaw.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte MARKUS RAST, PETER SKUFCA, WOLFRAM
STEINHILBER, GERHARD BECKER, JURGEN VOLZ,
and WOLFGANG ISE

_________________

Appeal 2018-007643
Application 14/068,074
Technology Center 1600
_________________

Before DEBORAH KATZ, JOHN G. NEW, and JOHN E. SCHNEIDER,
Administrative Patent Judges.

KATZ, Administrative Patent Judge.

DECISION ON APPEAL
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Appellant1 seeks our review2, under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 1–6, 8, and 9.3 (Appeal Br. 1.) We
have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.
Appellant’s Specification is directed to methods for preparing high
concentration liquid formulation of an antibody. (Specification (“Spec.”)
1:3.)
Appellant’s claim 1 recites:
A method for preparation of a high concentration liquid
formulation of a veltuzumab antibody or a fragment thereof,
having a concentration CH of the antibody, comprising the steps
of:
a) providing a solution containing the antibody in a starting
concentration CS;
b) ultrafiltering the solution of step (a) in order to obtain a
solution having an intermediate concentration C1 of the
antibody, wherein C1 is at least about 260 mg/mL; and
c) diluting the solution of step (b) to a concentration CH of
the antibody in order to obtain the high concentration liquid
formulation.

(App. Br. 15.)

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party-in-interest as TAKEDA GMBH. (Appeal Br. 3.)
2 We consider the Final Office Action issued August 11, 2017 (“Final Act.”),
the Appeal Brief filed January 18, 2018 (“Appeal Br.”), the Examiner’s
Answer issued on May 23, 2018 (“Ans.”), the Reply Brief filed July 12,
2018 (“Reply Br.”) and the oral argument held on September 17, 2019, in
reaching our decision.
3 Appellant canceled claims 7, 24 and 25 and withdrew claims 10–23, 26,
and 27 during prosecution. (See Appeal Br. 15–17.)
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The Examiner provisionally rejected claims 1–6, 8, and 9 under the
doctrine of obviousness-type double-patenting over claims 1–9 of copending
application 14/437,902 in view of Goldenberg4. (See Final Act. 3.) Because
none of the claims of application 14/437,902 have been determined to be
allowable, review of this rejection is premature. See Ex parte Moncla,
Appeal No. 2009-006448 (BPAI June 22, 2010) (precedential).
The Examiner also rejected claims 1–6, 8, and 9 as being obvious
under 35 U.S.C. § 103(a) over Yang5 and Goldenberg. (Final Act. 4–7.)
Appellant does not present arguments for the separate patentability of any of
these claims. Accordingly, we focus on claim 1 in our analysis. See 37
C.F.R. § 41.37(c)(1)(iv).
Findings of Fact
1. Yang teaches using filtration methods to obtain concentrated
antibody preparations. (See Yang abstract and 15:21–26.)
2. Yang teaches ultrafiltration of an anti-CD20 antibody to obtain
a formulation of antibody with a concentration in the range of 25–350
mg/ml. (See Yang 13:12–14.)
3. Yang teaches concentrating antibodies through ultrafiltration as
a final step before formulating the pharmaceutical to be administered. (See
Yang 15:21–24; 21:5–28; claims 22–41.)
4. Yang teaches that effective treatment with therapeutic
antibodies typically requires administration of doses concentrated to 100

4 Goldenberg et al. International Patent Application Publication WO
2010/011697 A1, published January 28, 2010 (“Goldenberg”).
5 Yang et al., International Patent Application Publication WO 2004/001007,
published December 31, 2003 (“Yang”).
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mg/ml or greater and that the concentration of antibodies in pharmaceutical
preparations is desirably between 100 and 300 mg/ml. (See Yang 2:15–32.)
5. Goldenberg teaches that the antibody veltuzumab was a known
antibody with improved efficacy compared to other anti-CD20 antibodies
such as rituximab. (See Goldenberg ¶¶ 180–180, Example 14.)
Analysis
Appellant’s claim 1 is drawn to providing an antibody solution of one
concentration, ultrafiltering it to achieve an intermediate concentration (at
least about 260 mg/ml), and diluting that intermediate concentration solution
to solution with a third concentration. (See Appeal Br. 15.) If it was known
in the art to use utrafiltration to achieve an antibody solution of at least 260
mg/ml and it would have been obvious to do so with veltuzumab, the only
other step in Appellant’s claim is diluting the antibody solution.
The Examiner finds that Yang teaches ultrafiltering an antibody
solution to obtain a concentration of up to 350 mg/ml. (See Final Act. 4 and
5, citing Yang 13.) The Examiner finds that Yang teaches antibodies can be
used therapeutically at lower concentrations: from 100 to 300 mg/ml. (See
Final Act. 4, citing Yang 2.) The Examiner finds further that Goldenberg
teaches the desirable attributes of veltuzumab. (See Final Act. 5.) We find
that the record supports these findings. (See FFs 1–5.)
The prior art shows that one of ordinary skill would have known how
to concentrate an antibody such as veltuzumab, to concentrations of at least
about 260 mg/ml by ultrafiltration. Appellant does not argue otherwise.
Thus, the issue before us is whether it would have been obvious to one of
ordinary skill in the art to dilute a solution of antibody concentrated by
ultrafiltration.
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The Examiner determines that because antibodies could be produced
at the higher concentration of 350 mg/ml and these antibodies could be used
at lower concentrations (100-300 mg/ml), it would have been obvious to
dilute these antibodies for therapeutic use. (See Final Act. 4–5.) We agree
with the Examiner.
Appellant argues that the “Examiner expressly acknowledges that
Yang does ‘not teach [the dilution] step c) of claim 1,’ or the use of
veltuzumab” and “cites nothing to fill this acknowledged gap in the cited
prior art.” (See Appeal Br. 8) But, Appellant also acknowledges that
formulating a preparation at the highest needed concentration and then
diluting it to prepare any lower concentrations needed “may be a reasonable
approach.” (Reply Br. 5.) We agree that such an approach would be
reasonable. It also would have been obvious.
Appellant’s argument that the rejected claims are directed to
production of one concentration of antibody at concentration “CH” and that
there is no need for antibody at any other concentration does not persuade us
to the contrary. (See Reply Br. 5.) If it is obvious to dilute a solution of
concentrated antibody, it does not matter what CH is or how it is used, as
long as it is lower to at least some extent than “at least about 26 mg/ml.”
We are not persuaded by Appellant’s argument that because the
Examiner stated that “Yang et al. do not teach step c) of claim 1 . . . .”
(Appeal Br. 8.) In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the
Supreme Court explained:
In many fields it may be that there is little discussion of
obvious techniques or combinations, and it often may be the
case that market demand, rather than scientific literature, will
drive design trends. Granting patent protection to advances that
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would occur in the ordinary course without real innovation
retards progress and may, in the case of patents combining
previously known elements, deprive prior inventions of their
value or utility.

(Id. at 419.) The Examiner’s reasoning that from the express teachings of
Yang it would have been obvious to dilute ultrafiltered formulations of
antibody is reasonable because there would be no other way to obtain
therapeutic concentrations from the highest ultrafiltered concentrations.
We disagree with Appellant’s argument that Yang does not teach
initially “over-concentrating” the formulation to a concentration higher than
ultimately desired. (Appeal Br. 10.) We also disagree with Appellant that
Yang focuses on providing the desired concentration directly. (See id. at
11–12.) Yang teaches ultrafiltering antibody solutions to achieve a
concentration of up to 350 mg/ml. (See FF 2.) Yang also teaches that
antibodies can be administered at lower concentrations: between 100 and
300 mg/ml. (See FF 4.) Thus, even if Yang does not use the word
“diluting,” those of ordinary skill in the art would know that the most
concentrated antibody formulations taught by Yang using ultrafiltration
would have to be diluted to obtain pharmaceutical formulations.
Appellant argues that “the claims clearly contemplate that the highest
needed concentration - the desired ‘high concentration liquid formulation
of a veltuzumab antibody or a fragment thereof - is at concentration cH.’”
(Reply Br. 4–5.) We are not persuaded by this argument because there is no
limitation to a “needed” concentration in Appellant’s claims. Appellant’s
claims recite on a starting concentration, an intermediate concentration, and
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a high concentration. Neither of them is recited to be “needed” or otherwise
therapeutic.
We are also not persuaded by Appellant’s argument questioning the
truth of the statement in Yang that concentrations as high as 350 mg/ml may
be prepared because there are no express teachings or examples of being
prepared and maintained. (Reply Br. 5.) “[B]oth claimed and unclaimed
materials disclosed in a patent are presumptively enabling.” In re Antor
Media Corp., 689 F.3d 1282, 1287 (Fed. Cir. 2012) (citing Amgen Inc. v.
Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1354 (Fed.Cir.2003)).
Appellant fails to present evidence to rebut this presumption. See Amgen
Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1355 (Fed. Cir. 2003)
(“The applicant, however, can then overcome that rejection by proving that
the relevant disclosures of the prior art patent are not enabled.”).
Appellant fails to persuade us that the Examiner erred. Accordingly,
we affirm the rejection under 35 U.S.C. § 103(a).

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Conclusion
Upon consideration of the record and for the reasons given, we affirm
the Examiner’s rejection.
In summary:
Claims
Rejected
Basis Affirmed Reversed
1–6, 8, and 9 Obviousness-
type double-
patenting6

1–6, 8, and 9 § 103 over
Goldenberg and
Yang
1–6, 8, and 9
Overall
Outcome
1–6, 8, and 9
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.

AFFIRMED

6 As explained above, we do not reach this rejection per Ex parte Moncla,
Appeal No. 2009-006448 (PTAB June 22, 2010) (holding that it is
premature to address a provisional rejection) (designated precedential).