Ex Parte Weigandt et al

Patent Trials and Appeals Board

Jun 20, 2019

14380989 - (D) (P.T.A.B. Jun. 20, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/380,989 08/26/2014
23599 7590 06/24/2019
MILLEN, WHITE, ZELANO & BRANIGAN, P.C.
2200 CLARENDON BL VD.
SUITE 1400
ARLINGTON, VA 22201
Markus Weigandt
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.
MERCK-4222 5630
EXAMINER
GOTFREDSON,GAREN
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
06/24/2019 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):
docketing@mwzb.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MARKUS WEIGANDT, SENTA VOSS, TOBIAS MILLER, and
ACHIM GOEPFERICH
Appeal 2018-004330
Application 14/380,989 1
Technology Center 1600
Before RYAN H. FLAX, RACHEL H. TOWNSEND, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a process
for the production of nanoparticles, which have been rejected as indefinite
and/or as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm-in-part.
STATEMENT OF THE CASE
Appellant's Specification explains that "[n]anoparticles based on
polymers can be produced using various processes" such as solvent
evaporation, co-solvent evaporation, dialysis and film hydration. (Spec. 2-
1 Appellant is Merck Patent GmbH, which is a wholly owned subsidiary of
Merck KGaA. (Appeal Br. 1.) Appellant identifies itself as the real party in
interest. (Id.)
Appeal 2018-004330
Application 14/380,989
4). According to Appellant's Specification "[p]roduction ofnanoparticles
with proven polymers by means of the[ se] processes ... often results in
active-compound loading which is inadequate for therapeutic use thereof."
(Id. at 4.) Appellant's Specification also states that "known processes also
result in nanoparticles from which the active compound is only released with
a certain time delay (lag time)." (Id.) Appellant's invention is directed to a
process of making an active compound laden nanoparticle that avoids the
disadvantages of the prior art. (Id. at 1, 5.)
Claims 1-20 are on appeal. Claim 1 is representative and reads as
follows:
1. Process for the production of nanoparticles comprising the
steps of
(a) dissolution of at least one active compound and at least one
polymer in an organic solvent,
(b) mixing of the solution prepared in step (a) with an aqueous
phase,
( c) evaporation of the organic solvent,
( d) purification of the nanoparticles laden with active
compound obtained in step ( c) by means of dialysis against
aqueous dialysis solution comprising the same active
compound.
(Supplemental Appeal Br. 3. )2
2 The Supplemental Appeal Brief was filed September 21, 201 7 in response
to a Notice of Non-Compliant Appeal Brief.
2
Appeal 2018-004330
Application 14/380,989
The following grounds of rejection by the Examiner are before us on
review:
Claims 6 and 20 under 35 U.S.C. § 112, second paragraph, as
indefinite for failing to particularly point out and distinctly claim the subject
matter which the inventor regards as the invention.
Claims 1, 4-13, 15-17, and 20 under 35 U.S.C. § 103 as unpatentable
over Letchford3 and Washington. 4
Claims 2, 3, 18, and 19 under 35 U.S.C. § 103 as unpatentable over
Letchford, Washington, and Elkharraz. 5
Claim 14 under 35 U.S.C. § 103 as unpatentable over Letchford,
Washington, and Koltenzburg. 6
DISCUSSION
Indefiniteness
In claim 6, the Examiner finds the language "additionally polyacrylic
acid and derivatives thereof, or polysiloxane and derivatives thereof' renders
the claim ambiguous as to whether the "polyacrylic acid and derivatives
thereof, or polysiloxane and derivatives thereof' are part of the group of
3 Letchford et al., A review of the formation and classification of
amphiphilic block copolymer nanoparticulate structures: micelles,
nanospheres, nanocapsules and polymersomes, 65 Eur. J. Pharmaceutics and
Biopharmaceutics 259-69 (2007).
4 C. Washington, Evaluation of non-sink dialysis methods for the
measurement of drug release from colloids: effects of drug partition, 56 Int'l
J. of Pharmaceutics 71-74 (1989).
5 Elkharraz et al., Paclitaxel-loaded microparticles and implants for the
treatment of brain cancer: Preparation and physicochemical
characterization, 314 Int'l J of Pharmaceutics 127-136 (2006).
6 Koltenzburg et al., US2007/0122436 Al, published May 31, 2007.
3
Appeal 2018-004330
Application 14/380,989
recited hydrophobic components of the block copolymer or whether they are
additional to the hydrophobic components. (Final Action 2-3.) Similarly, in
claim 20, the Examiner finds the language "furthermore
hydroxypropylethylacrylic acid, or hydroxypropylmethylacrylic acid,
polysiloxane and derivatives thereof' renders the claim ambiguous as to
whether the "hydroxypropylethylacrylic acid, or
hydroxypropylmethylacrylic acid, polysiloxane and derivatives thereof' are
part of the group of recited hydrophobic components of the block copolymer
or whether they are additional to the hydrophobic components. (Id.)
Appellant argues that the Supreme Court held that a claim is invalid
for indefiniteness "'if its claims, read in light of the specification delineating
the patent, and the prosecution history, fail to inform, with reasonable
certainty those skilled in the art about the scope of the invention."' (Reply
Br. 2 quoting Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120,
2129 (2014).) Appellant contends "that 'one skilled in the art would
interpret the language in claims 6 and 20 as defining the polyacrylic acid or
polysiloxane polymers as present in addition to the recited hydrophobic
components"' and thus the claims are not ambiguous when read in light of
the prosecution history. (Reply Br. 2 (quoting Appeal Br. 10.))
In determining whether a claim is definite under 35 U.S.C. § 112,
second paragraph, "[t]he USPTO, in examining an application, is obliged to
test the claims for reasonable precision." In re Packard, 751 F.3d 1307,
1313 (Fed. Cir. 2014); see also Ex parte McAward, Appeal 2015-006416,
2017 WL 3669566, at *5-6 (PTAB Aug. 25, 2017) (precedential). The
Office "determines the scope of claims ... upon giving claims their broadest
reasonable construction 'in light of the specification as it would be
4
Appeal 2018-004330
Application 14/380,989
interpreted by one of ordinary skill in the art."' Phillips v. AWH Corp., 415
F.3d 1303, 1316 (Fed. Cir. 2005) (en bane) (quoting In re Am. Acad. of Sci.
Tech Ctr., 367 F.3d 1359, 1364 (Fed. Cir. 2004)). While Appellant provides
attorney argument as to the meaning one of ordinary skill in the art would
ascribe to claims 6 and 20, "[a]ttorney's argument in a brief cannot take the
place of evidence." In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). We
agree with the Examiner's position that claims 6 and 20 are subject to
alternative interpretations making it unclear whether the "polyacrylic acid
and derivatives thereof, or polysiloxane and derivatives thereof' or the
"hydroxypropylethylacrylic acid, or hydroxypropylmethylacrylic acid,
polysiloxane and derivatives thereof' are part of the group of recited
hydrophobic components of the block copolymer or whether they are
additional to the hydrophobic components. In light of the foregoing lack of
clarity, we agree with the Examiner that there is a reasonable lack of
precision as to the metes and bounds of the claim. Thus, we agree with the
Examiner's conclusion that claims 6 and 20 are indefinite.
II
Non-Obviousness
The Examiner finds that Letchford teaches two processes for
production of nanoparticles that involve steps a and b as claimed. (Final
Action 4.) The Examiner explains further both processes involve removal of
solvent, but that one of the processes employs dialysis to remove the solvent
after the nanoparticles are formed, and the other removes solvent by
evaporation. (Id.) The Examiner contends that it would have been prima
facie obvious to use both the dialysis and evaporation steps in a single
process "to better remove the solvent, since ... it is prima facie obvious to
5
Appeal 2018-004330
Application 14/380,989
combine two process steps when both of them are taught by the prior art as
useful for achieving the same result (See In re Kerkhoven, 626 F.2d 846, 850
... (CCPA 1980) .... " (Id. at 6-7.)
The Examiner recognizes that in Appellant's claims, "the dialysis step
is conducted against an aqueous dialysis solution that comprises the same
active component that is loaded onto the nanoparticles." (Id. at 5.) The
Examiner contends that including such an active component in the aqueous
dialysis solution would have been obvious in light of the teachings of
Washington. (Id. at 6-7.)
According to the Examiner, Washington discloses that when a drug is
loaded onto a colloidal nanoparticle carrier, the drug concentration that
drives diffusion across the diffusion membrane is reduced compared to a
system that involves drug with no carrier. (Id. at 6.) The Examiner contends
that the reduction in concentration is "by a factor of the drug/carrier partition
coefficient since some of the drug remains loaded on the nanoparticle." (Id.)
The Examiner contends that "Washington makes it clear that in a solution
comprising a drug-loaded nanoparticle there will be an equilibrium between
free drug and drug loaded on the nanoparticle, and that the concentration of
free drug in a solution being used in a dialysis process will affect the
diffusion rate." (Id.) According to the Examiner, therefore, it would have
been obvious to one of ordinary skill in the art to include an active in the
dialysis solution to "help prevent loss of the active from the nanoparticle
carrier product during the dialysis caused by partitioning of the drug
between the nanoparticle carrier product during dialysis caused by
partitioning of the drug between the nanoparticles and the surrounding
solution." (Id. at 7.)
6
Appeal 2018-004330
Application 14/380,989
We disagree with the Examiner that it would have been obvious from
the disclosure of Letchford to combine an evaporation solvent removal step
with a dialysis solvent removal step as asserted by the Examiner. We do not
reach the issue of the obviousness as to the addition of the active in the
dialysis solution.
The Examiner's reliance on Kerkhoven in asserting that the
combination of an evaporation step and a dialysis step in solvent removal
would have been prima facie obvious (Final Action 7) is misplaced. In that
case, claims directed to a mixture of spray-dried anionic and spray-dried
nonionic surfactants were held to be prima facie obvious in view of prior art
describing the use of each of the surfactants in a spray-dried form.
Kerkhoven, 626 F .2d at 850 ("In the case at bar, [the] appealed claims ...
require no more than the mixing together of two conventional spray-dried
detergents. Thus, these claims set forth prima facie obvious subject
matter."). In other words, the case stands for the proposition that "[i]t is
prima facie obvious to combine two compositions each of which is taught by
the prior art to be useful for the same purpose, in order to form a third
composition which is to be used for the very same purpose." Id.
The issue here is, instead, whether it would have been obvious to
combine two different solvent evaporation steps in a single process for
forming drug loaded nanoparticles. While we do not agree that Kerkhoven
governs the outcome here, we consider "what the combined teachings of th[ e
prior art] references would have suggested to those of ordinary skill in the
art." In re Keller, 642 F.2d 413,425 (CCPA 1981). We conclude that it
would not have been obvious to combine dialysis solvent removal as taught
by Letchford after the evaporation solvent removal in the method of making
7
Appeal 2018-004330
Application 14/380,989
a drug loaded nanoparticle as taught by Letchford for the reasons explained
by Appellant. (Reply Br. 5; Appeal Br. 5.)
According to the Examiner, the use of the two different solvent
removal methods would have been obvious because it would result in a
process of better solvent removal. (Final Action 6.) Moreover, the
Examiner asserts that evaporation of a solvent can involve "either a water
miscible organic solvent or a water immiscible organic solvent." (Ans. 7-8).
However, as Appellant notes (Reply Br. 5), Letchford teaches that in
processes of making a drug loaded nanoparticle where the "copolymer is not
readily soluble in water," the dialysis method is used when the copolymer
and drug are solubilized in a water-miscible organic solvent to form the
nanoparticles, whereas solvent evaporation is used in conjunction with an
oil-in-water emulsion procedure to form the nanoparticles, which involves
the addition of a solution of the copolymer with the drug and a volatile, non-
water miscible organic solvent. (Letchford 262-63.) In each procedure for
forming the nanoparticles where the copolymer is not readily soluble in
water, a different type of organic solvent is used in the formation of the
nanoparticles, and thus a different solvent is required to be removed.
Consequently, we agree with Appellant (Reply Br. 5) that there would be no
reason to add the dialysis solvent removal step used to remove a water-
miscible solvent to Letchford's oil-in-water emulsion process that employs
solvent evaporation of a volatile, non-water miscible organic solvent to form
the drug loaded nanoparticles.
For the foregoing reasons, we do not sustain the Examiner's rejection
of claims 1, 4-13, 15-17, and 20 as being obvious.
8
Appeal 2018-004330
Application 14/380,989
In the remaining obviousness rejections, the Examiner relies on the
additional references to address dependent claim limitations, not the
obviousness of combining a dialysis step with the evaporation step. (See
Final Action 10.) Thus, for the reasons just discussed we also do not sustain
the Examiner's rejections of claims 2, 3, 14, 18, and 19.
SUMMARY
We affirm the rejection of claims 6 and 20 under 35 U.S.C. § 112,
second paragraph, as being indefinite.
We reverse the rejection of claims 1, 4-13, 15-1 7, and 2 0 under 3 5
U.S.C. § 103 as unpatentable over Letchford and Washington.
We reverse the rejection of claims 2, 3, 18, and 19 under 35 U.S.C.
§ 103 as unpatentable over Letchford, Washington, and Elkharraz.
We reverse the rejection of claim 14 under 35 U.S.C. § 103 as
unpatentable over Letchford, Washington, and Koltenzburg.
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. § l .136(a).
AFFIRMED-IN-PART
9