Ex Parte Schmidt et al

Patent Trial and Appeal Board

Mar 29, 2018

13201016 (P.T.A.B. Mar. 29, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/201,016 12/13/2011
21706 7590 03/29/2018
NOTARO, MICHALOS & ZACCARIA P.C.
100 DUTCH HILL ROAD
ORANGEBURG, NY 10962
FIRST NAMED INVENTOR
Timo Schmidt
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.
G80-059US 6390
EXAMINER
CLARKE, TRENT R
ART UNIT PAPER NUMBER
1651
MAILDATE DELIVERY MODE
03/29/2018 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 PATENT TRIAL AND APPEAL BOARD
Ex parte TIMO SCHMIDT, LOTHAR JUST,
FRANZ MASER, and HOLGER BECKER
Appeal2017-004712
Application 13/201,016
Technology Center 1600
Before DEMETRA J. MILLS, ULRIKE W. JENKS, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
JENKS, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellants 1 appeal from the
Examiner's decision to reject the claims as obvious and on the grounds of
nonstatutory obviousness-type double patenting. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
"[C]ryoprotectants protect the cells and their organelles from
membrane damage by ice crystals and from intracellular dehydration during
1 Appellants identify the real party in interest as Naturin GMBH & Co.
Br. 3.
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Application 13/201,016
the transition of water from the liquid to the crystalline phase." Spec. 2:9-
11. Collagen-based hydrogels have been used for cryopreservation of cells
but "have the drawback that they normally have thicknesses over 150 µm
which negatively affect cell vitality after thawing." Id. 3:26-27. The
collagen films that are less than 150 µm thick do not require that the cells
have to be detached "from the surface on which they were grown. This
increases both the survival rate and the vitality of the cells after thawing."
Id. 6:22-23.
Claims 1-5, 7, 8, 10-15, 17-20, and 22-24 are on appeal, and can be
found in the Claims Appendix of the Appeal Brief. Claim 1, the sole
independent claim, is representative of the claims on appeal, and reads as
follows:
Claim 1 : Method for the cryopreservation and long term
storage of one or several types of cells, cell constructs or three-
dimensional complex tissue[] assemblies comprising:
a) Providing a stable collagen cell carrier (CCC) made by a
process comprising partially drying a collagen
composition, the collagen cell carrier having, in its driest
state, a thickness of less than 20 µm, a mass per unit area
of 25 to 3 5 g/m2, and the following composition:
i) collagen [%weight]: 50 to 70,
ii) amide nitrogen [%weight]: 0.14 to 0.4,
iii) glycerol [%weight]: 12 to 35,
iv) fat[% weight]: 1 to 5,
v) sorbitol [%weight]: 0 to 20,
vi) water[% weight]: 5 to 40,
b) Seeding one or several types of cells, cell constructs or
three-dimensional tissue assemblies onto the collagen
cell carrier,
c) culturing the cells until their adherence to the collagen
cell carrier,
d) washing-off non adherent cells, and
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e) freezing the collagen cell carrier with adherent cells in a
freezing medium.
Br. 14 (Claims Appendix)(brackets in original).
The claims stand rejected as follows:
I. Claims 1-5, 7, 8, 10-15, 17-20, 23, and 24 under 35 U.S.C. § 103(a)
as unpatentable over Takezawa #1 2, Takezawa #2 3, Takezawa #3 4,
Chancellor5, Morgan 6, Voytik-Harbin 7 in light of Gerhardt. 8 Ans. 6.
II. Claims 1-5, 7, 8, 10-15, 17-20, and 22-24 under 35 U.S.C. § 103(a)
as unpatentable over Takezawa #1, Takezawa #2, Takezawa #3,
Chancellor, Morgan, Voytik-Harbin, and Gunasekaran9 in light of
Gerhardt. Ans. 11.
III. Claims 1, 3-5, 7, 10-15, and 17-20 as provisionally rejected on the
grounds of nonstatutory obviousness-type double patenting 10 over co-
2 Takezawa et al., JP2007-306856, publ. Nov. 29, 2007. In citing to this
reference we refer to the translation of record, see form 892 mailed Feb. 13,
2013 ("Takezawa #1").
3 Takezawa et al., Collagen Vitrigel: A Novel Scaffold That Can Facilitate a
Three- Dimensional Culture for Reconstructing Organoids; 13 CELL
TRANSPLANTATION 463-73 (2004)(" Takezawa #2).
4 Takezawa et al., Collagen vitrigel membrane useful for paracrine assays in
vitro and drug delivery systems in vivo, 131 J. BIOTECH. 76-83 (2007)
("Takezawa #3").
5 Chancellor et al., US 2006/0121006 Al, publ. June 8, 2006 ("Chancellor").
6 Morgan et al., WO 03/017770 Al, publ. Mar. 6, 2003 ("Morgan").
7 Voytik-Harbin et al., US 2008/0268052 Al, publ. Oct. 30, 2008
("Voytik-Harbin").
8 Gerhardt et al., VEGF guides angiogenic sprouting utilizing endothelial tip
cell filopodia, 161 J. CELL BIO. 1163-77 (2003)("Gerhardt").
9 Gunasekaran, US 2003/0203008 Al, publ. Oct. 30, 2003.
10 We note that the Final Action dated June 31, 2015, included a
nonstatutory obviousness-type double patenting over copending U.S.
Application No. 13/734,120, which has since been abandoned for failure to
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pending U.S. Application 12/705,682 11 and U.S. Application
13/734,120. Ans. 2.
I. and II. Obviousness
The Examiner finds that cryopreservation of cells seeded onto a
collagen matrix is taught in the art, but acknowledges that the compositional
limitations of the claimed collagen matrix was not described by these
cryopreservation references. See Ans. 7-8. The Examiner finds, and
Appellants do not rebut, that Morgan teaches a collagen matrix having the
requisite compositional requirements. Ans. 8, 18. Morgan's collagen matrix
is described as a sausage casing and the Examiner relies on Chancellor for
teaching that such collagen casings are known scaffolds that support cell
growth. See Ans. 8. The Examiner concludes that
a person of ordinary skill in the art at the time of the invention
would find it obvious to use the collagen casings taught by
Morgan in the methods of cryogenic storage of cells on a
collagen carrier as taught by Takezawa # 1 because Chancellor
teaches that collagen casings are excellent scaffolds for the
growth and proliferation of animal cells in tissue engineering
applications.
Ans. 10.
Appellants contend: 1) that Chancellor does not teach collagen
casings as a cell matrix (Br. 8); 2) that Morgan is not analogous art (Br. 9);
and that the rejection relies on hindsight (Br. 8 ("Turning the final product of
reply to an Office Action. Notice of Abandonment mailed Aug. 24, 2016.
The Examiner has now withdrawn this rejection. Ans. 13.
11 Just et al., US 2010/0233140 Al, publ. Sept. 16, 2010 ("the
'682 Application").
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cell culturing into a new substrate for additional cell culturing is a new and
hindsight-driven extension of Chancellor. Indeed, there is no evidence of
record that most collagen-based substances are well suited for cell
culture.")).
The issue is: Does the preponderance of evidence of record support
the Examiner's conclusion that the combination of references renders
obvious a collagen composition for use in the cryopreservation method as
claimed?
Findings of Fact
We generally agree with and adopt the Examiner's findings of fact
and reasoning regarding the scope and content of the prior art. See Ans. 6-
23 and Final Act. 12 3-13. For emphasis only we highlight the following:
FF 1. Takezawa # 1 teaches using a vitrigel thin membrane matrix
containing collagen in a method of freezing mouse embryonic stem
cells. See Takezawa #1 i-fi-f 15, 17, 32-37. Takezawa #1 teaches
producing vitrigel by platting a hydrogel solution and then drying the
composition once gelation ofhydrogel is complete. Takezawa #1 i1
15.
FF2. Morgan teaches producing collagen casings using a gel comprising
collagen, fat and humectant. Morgan, Abstract. Morgan teaches that
the "gel was extruded, and simultaneously inflated with air through an
annular extruder, to a wet wall thickness of approximately 0.4 mm
and 17 mm nominal diameter, onto a continuous support belt
contained within an ammonia gas chamber." Morgan 29. After
12 Final Office Action mailed July 31, 2015 ("Final Act.").
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extrusion the casing was dried, shirred, and moisture level adjusted to
"to around 20% prior to packing with the resultant weight measured to
be 2.6g/m." Morgan 29. The final casing constituents are listed in the
table below:
The table shows the percentage of collagen, glycerol, and fat
constituents in the casing made in experiments 13 and 14. Morgan 29.
The physical attributes of these exemplified casings are shown in the
table below:
EJ11:ampTe _____ _..,,..l_A ... -,e-ragecoict·····j1 saffi?T;;---------------- •·Ave~&~ :Burst · sam?ie-·--
i Tensile standard Weight from 5 s.tandard
! Strength fmm deviation of pieces deviation of
! 10 pi;~ ! CT frnm lO burst weight
----------- --------~ .. ~~~~~------------ .. • from 5_p~
13 ------- 9, l 5K ~· 0,63K · • ~Q.:.Q~-------------
14 0.12.. 0.6lK (L24K
Morgan 30.
FF3. Morgan teaches that "[t]he ratio of collagen to fat is at least 2.0: 1
(67% to 33%)," and specifies that "the fat content is not less than 3%
and especially not less than 1 % by weight." Morgan 4--5.
FF4. The Examiner finds that the collagen present in Morgan's
composition meets the claimed amide nitrogen limitation of 0 .14 to
0.4%. See Ans. 18. "Morgan's composition with 64.8% collagen
would give an amide nitrogen content of 0.28% amide nitrogen
(64.8% collagen from hides x 0.1787 total nitrogen x 0.0241 of total
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nitrogen is amide nitrogen= 0.279% amide nitrogen)." Ans. 18,
citing Mellon 13 .
FF5. The Examiner finds that Morgan's collagen casing has a mass per unit
area of approximately 39 .43 g/m2 and a dried thickness of 39 .4 µm.
See Ans. 9. To arrive at these numbers the Examiner provides the
following calculation:
Morgan teaches a resultant weight of 2.6 g/m with a
nominal diameter of21 mm (p. 29, steps 8, 9) which
gives 39.43g/m2 (circumference, 2rrr = 65.94mm;
2.6g/0.06594m2 =39.43g/m2 ) and 39.4 µm thickness
(39.4g at a density~ 1 g/lcm3 is approx. 39430mm3
volume per lm2 (1000000mm2 ) gives 39.4 µm
thickness).
Ans. 9.
FF6. Chancellor teaches using "cultured animal cells, either alone or in
combination with other ingredients, as components of nutritional
and/or therapeutic end products." Chancellor i-f 3.
Also contemplated by the present invention is the
use of MDC [(muscle-derived cells)]-seeded casings for
sausages, vegetarian sausages, and/ or other processed
food products. According to this aspect of the invention,
MDCs are seeded onto a matrix and the resulting
construct is used as a casing for sausage or a related
product. Commercially available sausage casings include
collagen casings, regenerated cellulose casings, and
natural casings comprised of intestinal submucosa. Two
of these materials, collagen and intestinal submucosa
(which itself contains collagen as a principal component),
have already been shown to function as excellent
13 Mellon et al., Determination of Amide Nitrogen in Collagen and Other
Proteins, 49 J. AMERICAN LEATHER CHEMISTS ASSOCIATION, 710-19 (1954),
of record see form 892 mailed Feb. 13, 2013.
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scaffolds for the growth and proliferation of animal cells
in tissue engineering applications. MDC-seeded casings
can be further built up from multiple layers of seeded
matrices in order to add thickness and integrity to the
casing. The MDC-containing casings can be filled with a
variety of edible products including, but not limited to,
conventional meat or poultry-based sausage material,
vegetarian sausage material, and sausage material
containing animal cells grown in vitro and processed in
accordance with any of the aforementioned methods and
descriptions.
Chancellor i-f 1 7.
Principle of Law
"If the claim extends to what is obvious, it is invalid under§ 103."
KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 419 (2007).
Analysis
The Examiner has rejected claims 1-5, 7, 8, 10-15, and 17-20 under
35 U.S.C. § 103(a) as being unpatentable over the combination of
Takezawa #1, Takezawa #2, Takezawa #3, Chancellor, Morgan, Voytik-
Harbin, and Gerhardt; and claims 1-5, 7, 8, 10-15, 17-20, and 22-24 over
the same references along with Gunasekaran. Because the same issue is
dispositive for both rejections, we consider these rejections together.
Further, the claims are not separately argued and we focus our discussion on
representative claim 1. See 37 C.F.R. § 41.37(c)(l)(iv).
After considering the evidence and the arguments, we conclude the
weight of the evidence favors the Examiner's conclusion of obviousness (see
Grounds of Rejection, Ans. 6-13; see FF1-FF6), and agree that the
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Examiner properly found Appellants' arguments unpersuasive (see Response
to Argument, Ans. 13-23). We address Appellants' contentions below.
Br. 8.
We are not persuaded by Appellants' contention that
Chancellor does not teach that collagen food casings are
excellent scaffolds for the growth and proliferation of animal
cells in tissue engineering applications, [and therefore,] it
would not be obvious to use the collagen sausage casing recipes
taught by Morgan in the method of cryogenic storage of cells
on a collagen carrier as taught by Takezawa # 1.
We agree with the Examiner's assessment that Chancellor teaches that
collagen materials are excellent scaffolds for cell proliferation. See Ans. 8;
FF6 ("collagen and intestinal submucosa (which itself contains collagen as a
principal component), have already been shown to function as excellent
scaffolds for the growth and proliferation of animal cells in tissue
engineering applications"). Furthermore, Chancellor teaches that
commercially available casings include collagen casings. See FF6.
("Commercially available sausage casings include collagen casings,
regenerated cellulose casings, and natural casings comprised of intestinal
submucosa"). Chancellor also teaches that seeding cells onto these type of
casings can improve their integrity. See FF6 ("MDC-seeded casings can be
further built up from multiple layers of seeded matrices in order to add
thickness and integrity to the casing"). Based on these teachings in
Chancellor, we find no error with the Examiner's conclusion that the casings
taught by Morgan (FF2-FF3) would likewise be a suitable matrix for cell
seeding and cell proliferation purposes. See Ans. 10, 14.
We further agree with the Examiner that substituting Morgan's
collagen casing matrix (seeded with cells) for the vitrogel matrix (likewise
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seeded with cells) that is used in the cryogenic storage method taught in
Takezawa # 1 would be obvious because it amounts to exchanging one prior
art element for another that achieves the same result; in this case, the matrix
serves as a substrate to attach cells during growth and proliferation. See
KSR, 550 U.S. at 416, citing United States v. Adams, 383 U.S. 39, 50-51
(1966); see In re Fout, 675 F.2d297, 301, (CCPA 1982)("Express
suggestion to substitute one equivalent for another need not be present to
render such substitution obvious."); see also In re Mayne, 104 F.3d 1339,
1340 (Fed. Cir. 1997) ("Because the applicants merely substituted one
element known in the art for a known equivalent, this court affirms [the
rejection for obviousness]."). We find no error with the Examiner's
combination.
We are also not persuaded by Appellants' contention that Morgan is
not analogous art. Br. 9.
Two criteria have evolved for determining whether prior art is
analogous: (1) whether the art is from the same field of
endeavor, regardless of the problem addressed, and (2) if the
reference is not within the field of the inventor's endeavor,
whether the reference still is reasonably pertinent to the
particular problem with which the inventor is involved.
In re Clay, 966 F.2d 656, 658-59 (Fed. Cir. 1992). Here, the Examiner has
established that Chancellor teaches that collagen casings can be used to host
cell proliferation; the references is therefore reasonably pertinent to the
problem of proliferating cells on a collagen scaffold matrix for the purpose
to tissue engineering. FF6. This teaching connects Morgan's collagen
casings as a substrate for cell proliferation (FF2-FF3) with the teachings of
Takezawa # 1 that teaches using a collagen membrane matrix, namely
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vitrogel, for proliferating cells and subsequently preserving those cells by
freezing. FF 1. Even though the art may not be from the same field of
endeavor, there is sufficient evidence in the record to establish that the art is
reasonably pertinent to the problem of finding a substrate for attaching and
proliferating cells. Having found no error in the combination of references
as proposed by the Examiner (see Ans. 10, 14), we are not persuaded by
Appellants' intimation that Morgan does not teach that collagen food casings
are excellent scaffolds for the growth and proliferation of animal cells in
tissue engineering applications because this argument does not take into
account the teachings of Chancellor. See Ans. 10; see FF6.
We are also not persuaded by Appellants' hindsight contention. Br. 9.
We agree with the Examiner's position and conclusion as set out in the
Answer. See Ans. 19. While we are fully aware that hindsight bias often
plagues determinations of obviousness, Graham v. John Deere Co., 383 U.S.
1, 3 6 ( 1966), we are also mindful that the Supreme Court has clearly stated
that the "combination of familiar elements according to known methods is
likely to be obvious when it does no more than yield predictable results."
KSR, 550 U.S. at 416. The Examiner has directed us to sufficient evidence
in the record to establish that the references teach the elements either
directly of inherently to support a conclusion of obviousness. See FF1-FF6.
We find no evidence, and Appellants have not directed us to any evidence,
that the Examiner relied on teachings found only in the Specification to
arrive at the claimed invention. Therefore, we are not persuaded by a
Appellants' hindsight argument.
We affirm the rejection of claim 1 for reasons set out above and those
presented by the Examiner in the Answer and Final Office Action. As
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claims 2-5, 7, 8, 10-15, 17-20, and 22-24 were not argued separately, we
affirm the rejection of those claims as well. See 37 C.F.R. § 41.37(c)(l)(iv).
III. Obviousness-Type Double-Patenting
The issue is: Does the preponderance of evidence of record support
the Examiner's conclusion that it would have been obvious to subject the
cell-seeded collagen composition taught in the '682 Application to the
cryopreservation method as claimed?
Findings of Fact
FF7. Claim 1 of co-pending U.S. Patent Application No. 12/705,682 is
reproduced below:
1. A method for the cultivation of biological material,
comprising the following steps:
(1) Providing a composition suitable for use as a carrier
for biological material,
(2) Contacting said biological material with said
composition, and
(3) Incubating said composition with said biological
material under cultivation conditions, wherein said
composition comprises the following parameters:
Coll a.gen [\vt.-i~.;J]:
.. :.\rnEdt nitrog'Cn [v . .rt~ ... 1:~.·~i].:
Pvlyo1 [wt.-'h,]:
FM [wt . .-'}t.j:
Ash [wt.-'hi]:
\Vatcr ['>:vt-;% I:
pH\'hlu~:
\Vdghr pi::T ~.wit a~rea fg/n?J:
T.;.msik~ stn:\ngth [N/mm2 j:
'682 Application, 7 (claim 1).
12
approx. 30 ro 80,
approx. 0.06 to 0.{),
approx. r) to 5(J,
approx. D k.• 20,
approx. 0 t:c, 10,
approx. 5 to 4U,
approx. 3 to 10.,
approx. 1 O lo 100,
apprnx. 0.5 t:D !!)[!.
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Analysis
Appellants contend that "Takezawa #1 teaches (exhaustively) drying a
(different) collagen composition" and does "not describe making collagen
cell substrates by a process of partially drying a collagen composition."
Br. 12. Appellants further argue:
It might, arguendo, be obvious to try a cell culture substrate
from a first application and use it in a different second
application in some circumstances. Even where that is the case,
however, it is not obvious to arbitrarily add new process steps
(e.g. drying) to the method of manufacturing the cell culture
substrate being imported from the first application, in order to
replicate the Applicant's claimed method.
Br. 12.
We are not persuaded. Appellants' arguments are directed at a
combination not proposed by the Examiner; namely, that it would have been
obvious to modify the vitro gel production as taught by Takezawa # 1 in order
to arrive at the presently claimed matrix. The Examiner instead relies on the
teaching of Takezawa # 1 and the teaching of the '682 Application to
establish that the matrixes are both shown to be suitable substrates for the
purpose of cell culture and, therefore, that it would have been obvious to
substitute the '682 Application matrix (FF7) for the vitro gel matrix in the
cryopreservation method taught by Takezawa #1. FFI. See Ans. 23 (the
rejection "is based on the collagen cell carriers of Takezawa #1 and '682
both being suitable substrates for culturing cells"). In other words, the
Examiner finds it obvious to substitute one element for another known in the
art that is used for the same purpose. See KSR, 550 U.S. at 416, citing
United States v. Adams, 383 U.S. 39, 50-51 (1966).
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We are also not persuaded by Appellants' contention that the '682
Application does "not describe making collagen cell substrates by a process
of partially drying a collagen composition." Br. 12. "The patentability of a
product does not depend on its method of production. If the product in a
product-by-process claim is the same as or obvious from a product of the
prior art, the claim is unpatentable even though the prior product was made
by a different process." In re Thorpe, 777 F.2d 695, 697 (Fed. Cir. 1985)
(internal citations omitted). Here, the matrix carrier used in the '682
Application contains overlapping collagen, amide nitrogen, polyol, fat, and
water content to the matrix carrier of the present claims. Compare claim 1
and FF7. Based on the similarities of the carrier composition, including the
overlapping water content, we find that the evidence in the record is
sufficient to support the Examiner's conclusion that it would have been
obvious to subject the cultivated biological material of the '682 Application
to further cryopreservation steps as suggest by Takezawa # 1 to arrive at the
claimed method.
SUMMARY
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
unpatentable over Takezawa #1, Takezawa #2, Takezawa #3, Chancellor,
Morgan, Voytik-Harbin, and Gerhardt. Claims 2-5, 7, 8, 10-15, 17-20, 23,
and 24 were not separately argued and fall with claim 1.
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
unpatentable over Takezawa #1, Takezawa #2, Takezawa #3, Chancellor,
Morgan, Voytik-Harbin, Gunasekaran, and Gerhardt. Ans. 11. Claims 2-5,
7, 8, 10-15, 17-20, and 22-24 were not separately argued and fall with
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claim 1.
We affirm the provisional obviousness-type double patenting rejection
of claim 1 over copending U.S. Applications 12/705,682 and Takezawa #1.
Claims 3-5, 7, 10-15, and 17-20 were not separately argued and fall with
claim 1.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 3 7 C.F .R. § 1.13 6( a )(1 )(iv).
AFFIRMED
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