Ex Parte Pedrozo et al

Patent Trial and Appeal Board

Feb 6, 2019

12540489 (P.T.A.B. Feb. 6, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/540,489 08/13/2009
84398 7590 02/08/2019
McCarter & English / KCI
265 Franklin St.
Boston, MA 02110
FIRST NAMED INVENTOR
Hugo Pedrozo
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.
TRS.OlOOUS 1425
EXAMINER
POPA, ILEANA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
02/08/2019 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):
docket@mccarter.com
mvaneman@McCarter.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HUGO PEDROZO, EDWARD S. GRIFFEY, and
CHRISTOPHER R. KAUFMANN
Appeal2017-009691
Application 12/540,489
Technology Center 1600
Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and
ULRIKE W. JENKS, Administrative Patent Judges.
JENKS, Administrative Patent Judge.
DECISION ON APPEAL
Appellants 1 submit this appeal2 under 35 U.S.C. § 134(a) involving
claims directed to a method of preparing a tissue scaffold and a tissue
scaffold product. Examiner rejected the claims as indefinite and obvious. We
have jurisdiction under 35 U.S.C. § 6(b ).
We affirm-in-part.
1 Appellants identify the Real Party in Interest as KCI Licensing. Appeal
Br. 1.
2 We have considered, and herein refer to, the Non-Final Office Action of
March 10, 2016 ("Office Act."); Appeal Brief of January 9, 2017 ("Appeal
Br."); Examiner's Answer of May 9, 2017 ("Ans."); and Reply Brief of July
6, 2017 ("Reply Br.").
Appeal2017-009691
Application 12/540,489
STATEMENT OF THE CASE
Claims 1-6, 8-11, 13-19, 30, and 46 are appeal, and can be found in
the Claims Appendix of the Appeal Brief. Claim 1 is representative of the
claims on appeal, and reads as follows:
1. A method of preparing a tissue scaffold, comprising:
adding an acellular tissue matrix to at least one aqueous
solution comprising sodium acetate;
incubating the acellular tissue matrix in the at least one
aqueous solution comprising sodium acetate;
mechanically homogenizing the acellular tissue matrix
and solution to form a slurry containing acellular tissue matrix;
cooling the slurry;
casting the slurry containing the homogenized acellular
tissue matrix m a casting container;
cooling the slurry in an environment of about -70°C or less
to freeze the slurry;
and lyophilizing the slurry to produce a tissue scaffold of
acellular tissue matrix having a porosity of about 7 5% to about
90%.
Examiner rejects the claims as follows:
I. Claim 14 under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA),
second paragraph, as having insufficient antecedent basis for the
limitation of "the second aqueous sodium acetate solution" as
claimed. 3
3 Appellants acknowledge this rejection but do not provide any substantive
arguments, merely indicating that they will address the issue upon indication
of allowable subject matter. See Appeal Br. 10. We, therefore, summarily
affirm this rejection for the reason set out by Examiner in the Non-Final
Office Action and Answer. See MPEP § 1205.02
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Application 12/540,489
II. Claims 1, 3---6, 9--11, 14, 16-19, 30, and 46 under 35 U.S.C. § 103(a)
as unpatentable over Snowden, 4 in view of Silver, 5 Huang, 6
Abraham, 7 and Ju. 8
III. Claims 1, 3-6, 9--11, 13-19, and 30 under 35 U.S.C. § 103(a) as
unpatentable over Snowden, in view of Silver, Huang, Abraham, Ju,
and further in view of Chu. 9
IV. Claims 1, 3---6, 8-11, 14--19, and 30 under 35 U.S.C. § 103(a) as
unpatentable over Snowden, in view of Silver, Huang, Abraham, Ju,
and further in view of O'Brien 10 and Dagalakis. 11
V. Claims 1-6, 9--11, 14, 16-19, and 30 under 35 U.S.C. § 103(a) as
unpatentable over Snowden, in view of Silver, Huang, Abraham, Ju,
and further in view of Padmini. 12
Obviousness over Snowden, Silver, Huang, Abraham, and Ju
Examiner rejected all of the claims on appeal (see II.-V.) under 35
USC§ 103(a) as obvious based on the underlying combination of Snowden,
4 Snowden, US 2006/0149040 Al, published July 6, 2006 ("Snowden").
5 Silver et al., US 4,703,108, issued Oct. 27, 1987 ("Silver").
6 Huang, US 7,498,412 B2, issued Mar. 3, 2009 ("Huang").
7 Abraham et al., US 5,993,844, issued Nov. 30, 1999 ("Abraham").
8 Y. Ju et al., Beneficial Effect of Hydrophilized Porous Polymer Scaffolds In
Tissue-Engineered Cartilage Formation, 85B J BIOMED. MATER. RES.PART
B: APPL. BIOMATER. 252-260 (2008) ("Ju").
9 Chu et al., WO 90/00060, published Jan. 11, 1990 ("Chu").
1° F.J. O'Brien, The effect of pore size on cell adhesion in collagen-GAG
scaffolds, 26 BIOMATERIALS 433--441 (2005) ("O'Brien").
11 N. Dagalakis et al., Design of an artificial skin. Part III. Control of pore
structure, 14 J. Biomedical Mater. Res. 511-528 (1980) ("Dagalakis").
12 Padmini et al., US 2005/0260612 Al, published Nov. 24, 2005
("Padmini").
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Application 12/540,489
Silver, Huang, Abraham, and Ju. Specifically, Examiner relied upon the
teaching of Snowden, Silver, Huang, Abraham, and Ju to teach the
production of a tissue scaffold having a porosity of about 75% to about 90%.
Because the same issue is dispositive for all of these rejections (see II.-V.),
we will consider the rejections together.
Examiner finds that "Snowden teaches a method of making a collagen
sponge (i.e. a porous tissue scaffold)," specifically, noting that Snowden
prepares a collagen dispersion made from an animal skin. Ans. 3.
Snowden's process begins by incubating the skin in a buffer comprising
"acetic acid adjusted to pH 3.2-4.5 with anhydrous sodium acetate or
sodium hydroxide." Id. Examiner finds that Snowden applies the collagen
processing and drying techniques taught in Silver. Id. at 4. Examiner
acknowledges that together Snowden and Silver "teach re-suspending the
pelleted purified collagen in an organic acid solution and not in the buffer
containing sodium acetate." Id. Sodium acetate is required by the claim.
Examiner relies on Huang for including sodium acetate into a collagen
processing buffer, specificallynoting that Huang suggests that a sodium
acetate stabilizes collagen matrix. Id. Based on this teaching, Examiner
concludes that "[ o ]ne of skill in the art would have found obvious to modify
the method of Snowden and Silver ... by replacing their dermis with a
human or a porcine dermal acellular matrix as the source of insoluble
collagen to achieve the predictable result of obtaining a collagen scaffold."
Office Act. 5.
The issue is: Does the preponderance of evidence of record support
Examiner's conclusion that the combination of references renders the
method of producing a tissue scaffold as claimed obvious?
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Application 12/540,489
Principle of Law
"[E]xaminer bears the initial burden, on review of the prior art or on
any other ground, of presenting aprimafacie case ofunpatentability." In re
Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). A prima facie case for
obviousness "requires a suggestion of all limitations in a claim," CFMT, Inc.
v. Yieldup Int 'l Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003) and "a reason
that would have prompted a person of ordinary skill in the relevant field to
combine the elements in the way the claimed new invention does." KSR
Int'! Co. v. Teleflex Inc., 550 U.S. 398,418 (2007).
Analysis
Appellants contend that "the purpose of Snowden is to produce a
purified collagen product." Appeal Br. 11. Appellants contend that the end
product of the present claims includes a tissue matrix reciting a particular
level of porosity and this is not taught in either Snowden or Silver. See id. at
12. Appellants contend that Examiner's reliance on Huang "is misplaced"
because Huang recites the use of sodium acetate as one of a number of salt
additives that can be used in a softening solution. See id. Specifically, Huang
teaches that with the addition of salt to the softening solution, "the best
effect for stabilizing the connective tissue matrix can be achieved and the
best porosity can be obtained." Id. at 13-14. Appellants contend that
Examiner has not provided an articulated a rationale why it would have been
obvious to substitute an acellular tissue matrix for the dermis taught in the
process of Snowden. Id. at 14. Because, "[t]o do so would defeat the purpose
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of the extraction process, which is intended to produce a purified collagen
product." Id. at 15.
Snowden teaches a method of producing collagen from animal skin.
See Snowden, Abstract. Snowden's method applies an organic acid buffer
including sodium acetate to the animal skin that is then "allowed to incubate
for sufficient time to enable the wool or hair to be loosened or removed." Id.
,r 14, see also ,r 3 6 (Buffer is "applied to the skin by spraying, painting, or
dipping."). "The most preferred buffer is composed of 40% (w/w) glacial
acetic acid in water and the pH adjusted to the preferred pH ( 4.0-4.2) by
addition of around 20% anhydrous sodium acetate or the required amount of
sodium hydroxide." Id. ,r 36. Once wool or hairs are removed from the skin
(id. ,r 41 ), the pelt is then chop or minced into small pieces using industrial
mincers, grinders, or food processors. Id. ,r 42, see also id. ,r 59 ("The pelt
was then washed with water and chopped into small pieces using an
industrial grade food processor."). "The pelt pieces are then added to a non-
denaturing solution to produce a suspension." Id. ,r 43, see also id. ,r 60 ("a
non-denaturing solution comprising 0.1 M acetic acid."). To this non-
denaturing solution Snowden then adds a protease. Id. ,r 46. After further
incubation, the soluble collagen and the dispersed collagen can be separated
by centrifugation. Id. ,r 49. The dispersed collagen can be washed with water
and then dried, including freeze-drying. See id. ,r,r 52-53. Alternatively, "the
collagen can be redispersed with organic acid, and this dispersion can then
be used to form a collagen matrix or sponge by freeze-drying in the Silver
[sic] et al. US 4,703,108." Id. f 17.
Silver teaches using insoluble collagen solutions dispersed and
swollen in a liquid media such as dilute hydrochloric acid or dilute acetic
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acid, that is then frozen and subjected to vacuum drying in order to form a
collagen based sponge. Silver 3: 17-26.
Huang teaches the production of a porous collagen matrix. Huang
4:20-22. Specifically, Huang teaches "an in situ process, which maintain
some structural scaffold of the collagenous tissue matrix, and to utilize said
process for preparing a porous collagen matrix from connective tissue." Id.
3 :49-52. Huang discloses that the source of connective tissue may be
derived from animal connective tissue including pigs. Id. 4: 44--46. The
process treats connective tissue "with a softening solution so that the
connective tissue can be softened." Id. 5: 17-20. The softening step taught in
Huang includes organic acid such as acetic acid among others. See id. 5 :20-
26. Huang teaches salts can be added to the softening solution in order "to
stabilize collagen molecules to create a better porous structure in the
matrix." Id. 5:63---64. Salts contemplated by Huang include organic salts
such as sodium acetate among others. Id. 6:5. Huang also teaches the use of
a poring agent to treat the connective tissue so that pores can be formed
inside the connective tissue. Pouring agents include oxidants, peroxidants
acids or bases. Id. 6:15-18. Huang also teaches that the dermal tissue treated
with the softening solution can be frozen and lyophilized after washing the
structure to remove residual chemical agents. See id. 8:40---63 (example 5).
Appellants contend that Examiner has not provided an articulated
rationale why it would have been obvious to substitute an acellular tissue
matrix of Huang for the dermis taught in the process of Snowden. Appeal
Br. 14. Because, "[t]o do so would defeat the purpose of the extraction
process, which is intended to produce a purified collagen product." Id. at 15.
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We find that Appellants position is supported by the evidence. Huang
teaches the production of an acellular tissue matrix that retains the original
shape. Huang 3:49--52 ("maintain some structural scaffold of the
collagenous tissue matrix"). The collagen scaffold in Huang is washed with
phosphate buffered saline in order to remove any residual chemical agents
before freezing and lyophilizing the structure. Id. 8:55-58. We agree with
Appellants that Huang, therefore, doesn't give a reason why one of ordinary
skill in the art would want to take the lyophilized acellular matrix taught in
Huang, that is specifically produced to retain the original structure, and then
add this matrix into step one of Snowden's process (applying an organic acid
buffer including sodium acetate to extract collagen from animal skin).
Snowden, ,r 9, 33. As Appellants point out, the purpose of Snowden is to
extract collagen from animal skin, but there is no reason in Snowden, or
articulated by Examiner, that would suggest to start the process with an
acellular collagen matrix. In other words, what is missing from Examiner's
rationale is a reason to start Snowden's process with a product that has
already been acellularized.
To establish obviousness, there must be "an apparent reason to
combine the known elements in the fashion" recited in the claims. KSR Int 'l
Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). Examiner acknowledges that
together Snowden and Silver "teach re-suspending the pelleted purified
collagen in an organic acid solution and not in the buffer containing sodium
acetate." Ans. 3. Examiner relies on the teaching Huang for including
sodium acetate in a buffer for the purpose of stabilizing collagen. Id. Hwang
teaches that"[ w ]hen 0.1 to 2M of sodium chloride is added to the softening
solution, the best effect for stabilizing the connective tissue matrix can be
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Application 12/540,489
achieved and the best porosity can be obtained." Huang 6:5-8, see id. 6:5
(Organic salts include sodium acetate). Even though Huang suggests that
salt, such as sodium acetate, could also be used in the softening solution,
there is no indication in Huang that applying a softening solution to a
collagen sponge such as the one taught in Snowden would result in a product
that has better stability and porosity.
Here, Huang discloses a method that retains the collagen structure of
the original tissue and removes the cells that surround this collagen
structure. It appears that the reference to the "best porosity" obtained in
Huang is discussing the ability to stabilize the connective tissue matrix itself
while removing the cellular material that surrounds the collagen. See Huang
6:5-8. Huang further discloses the use of poring agents in order to form
pores inside the connective tissue. See id. 6:15-16. Thus, we recognize that
Huang discloses the application of softening solution that helps stabilize
connective tissue matrix, whose original structure is being maintained. This
teaching in Huang, however, does not disclose that the application of the
same softening solution would have the same effect using the collagen
sponge disclosed in Snowden and Silver because the collagen sponge does
not retain any original structure that needs to be preserved and stabilized.
Accordingly, we agree with Appellants contention that Examiner has not
provided a sufficiently articulated rationale in order to arrive at a conclusion
of obviousness.
Examiner relies on Abraham for teaching human and porcine dermal
acellular matrixes. Ans. 5. Examiner concludes that
One of skill in the art would have readily understood that
using the collagenous acellular tissue matrices of Abraham et al.
would render moot the steps of extracting collagen from skin, as
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Id.
the acellular tissue matrices themselves would constitute the
purified collagen. Thus, by modifying the method of Snowden,
Silver et al., and Huang et al. as stated, one of skill in the art
would have re-suspending the acellular dermal matrix in the
acetate buffer to obtain a collagen dispersion and would have
further processed this collagen dispersion by homogenization to
obtain a slurry, transferring the slurry to a container cooling to
OQC, freezing at less -70 QC, and lyophilizing the slurry to
obtain the porous collagen scaffold.
Appellants contend that the sodium acetate "buffer is 'applied to the
flesh side of a fresh animal skin."' Appeal Br. 12. "It is the removed
collagen, which is no longer in the presence of sodium acetate, that is used
to form a collagen matrix or sponge by freeze-drying in the manner
disclosed in Silver." Id. at 12-13. In other words, simply substituting
Abraham's acellular matrix into Snowden or Silver's casting process does
not lead one of ordinary skill to arrive at a slurry that contains sodium
acetate as claimed. We agree with Appellants position that substituting
Abraham's matrix into the casting process of Snowden or Silver still does
not provide a reason to include sodium acetate in this casting process.
Examiner relies on Ju's teaching of "making porous scaffolds for
tissue engineering by adding sodium bicarbonate to polymer solutions to
obtain scaffolds with a porosity of 87-93% and pores having uniform
structure." Ans. 6. Examiner concludes that it would have been obvious to
one of ordinary skill in the art to include sodium bicarbonate in the collagen
dispersion before the homogenization step in order to obtain a highly porous
scaffold for tissue engineering. See id. at 6-7. Examiner also identifies that
Ju teaches scaffolds having a porosity of 87 to 93 % which overlap with the
claimed range of 75 to 90%. Id. at 7.
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Appellants contend that Examiners reliance on Ju is also misplaced.
See Appeal Br. 15-16. Specifically, arguing that Examiner has not identified
any teaching in the prior art that suggests a porosity level as recited in the
claim would provide a desired result. See id. at 1 7.
Ju teaches the production of three-dimensional porous poly(L-lactic
acid) (PLLA) scaffolds. Ju Abstract. "Compared to the natural scaffolds,
synthetic scaffolds permit the use of a variety of techniques to fabricate
porous scaffolds. They include solvent casting and particulate (SC/PL),
fabrication of a nonwoven sheet, phase separation, gas foaming, emulsion
freeze drying, and 3D printing." Id. at 252. Ju teaches that collagen is a
natural polymer scaffold. Id.
We find Appellants have the better position. Here, Ju teaches that its
collagen is a natural polymer and that natural polymers differ from the
synthetic polymers. See Ju 252. Most notable, Ju teaches that certain
manipulation techniques, such as gas foaming, that can be applied to
synthetic polymers cannot be readily applied to the production of natural
polymer scaffolds. Id. Collagen matrix serves as a natural polymer scaffold.
Examiner has not articulated a sufficient rationale why Ju's gas forming
technique applied to a synthetic polymer can reasonably be extrapolated be
applicable to a natural collagen matrix contrary to the teaching in Ju.
We conclude that the preponderance of the evidence of record does
not support Examiner's conclusion that the combination of Snowden, Silver,
Huang, Abraham, and Ju teaches a method for producing a collagen matrix
having all limitations of independent claims 1 and 30. Thus, we reverse each
of the rejections under 35 U.S.C. § 103(a) that rely on the underlying
teachings of Snowden, Silver, Huang, Abraham, and Ju.
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SUMMARY
We affirm the rejection of claim 14 under 35 U.S.C. § 112(b) or 35
U.S.C. § 112 (pre-AIA), second paragraph.
We reverse all obviousness rejections under 35 U.S.C. § 103(a) as
unpatentable over Snowden, Silver, Huang, Abraham, and Ju in combination
alone or in further combination Chu, 0 'Brien, Dagalakis, or Padmini.
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-IN-PART
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