Ex Parte Yoo et al

Patent Trial and Appeal Board

Oct 29, 2018

12293490 (P.T.A.B. Oct. 29, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/293,490 04/23/2009
20792 7590
MYERS BIGEL, P.A.
PO BOX 37428
RALEIGH, NC 27627
10/29/2018
FIRST NAMED INVENTOR
James Yoo
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.
9865-78 1592
EXAMINER
NGUYEN, NGHI V
ART UNIT PAPER NUMBER
1653
MAIL DATE DELIVERY MODE
10/29/2018 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
Exparte JAMES YOO, TAO XU, and ANTHONY ATALA 1
Appeal2017-007618
Application 12/293 ,490
Technology Center 1600
Before RICHARD J. SMITH, TA WEN CHANG, and
DAVID COTTA, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of printing fibroblasts and keratinocytes to form a skin tissue. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Background
"Although the capability of inkjet printing of viable single cells has
been verified, the possibility of simultaneously printing multiple cell types to
1 According to Appellants, the real party in interest is Wake Fore st
University Health Sciences. (Appeal Br. 3.)
Appeal2017-007618
Application 12/293,490
build viable heterogeneous cellular constructs has not been demonstrated to
date." (Spec. 1, 11. 25-27.)
"It has been found that distinct cell types can be mixed with support
compounds (collagen gels) and printed into the target areas to form 3-
dimensional tissue structures." (Id. at 11. 27-29.)
Claims on Appeal2
Claims 1, 2, 4, 12-14, and 17-22. (Claims Appendix, Appeal Br. 12-
14.) Claims 1 and 20 are illustrative and read as follows (emphasis and
formatting added):
1. In a method of forming an array of viable cells by ink-jet
printing a cellular composition containing said cells on a
substrate, the improvement comprising:
printing at least two different types of viable mammalian
cells on said substrate, said at least two different types of viable
mammalian cells selected to together form a tissue;
wherein said tissue is skin tissue.
20. A method of forming a skin tissue, comprising:
providing a first composition comprising fibroblasts and a
support compound;
ink-jet printing said first composition on a substrate to
form a first layer;
providing a second composition comprising keratinocytes;
and
ink-jet printing said second composition comprising
keratinocyes onto said first layer, wherein said fibroblasts and
keratinocytes together form a skin tissue on said substrate.
2 Applicants elected the species of tissue (skin), cell types (keratinocytes,
fibroblasts, and melanocytes ), and "does further comprise implanting the
array in vivo" (see claim 12) without traverse. (Final Action dated Oct. 27,
2015 ("Final Act.") at 2.) We limit discussion and consideration to the
elected species. See Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (Bd. Pat. App.
Int. 1987).
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Application 12/293,490
Examiner's Rejections
1. Claims 1, 4, 12, 17, and 19--22 stand rejected under 35 U.S.C.
§ I03(a) as unpatentable over Gruskin3 and Forgacs. 4 (Final Act. 3--4.)5
2. Claims 1, 2, 4, 12-14, and 17-19 stand rejected under 35 U.S.C.
§ I03(a) as unpatentable over Boland, 6 Harmon,7 Burg, 8 and Sabolinski. 9
(Final Act. 5-8.)
FINDINGS OF FACT
The following findings are provided for emphasis and reference
purposes.
FF 1. The Examiner finds that Gruskin teaches making synthetic skin
comprising the steps of seeding human fibroblast cells, with collagen, onto a
support, and seeding a second layer of human keratinocytes onto the
fibroblasts on the support, followed by implantation into a subject such as a
bum victim. (Final Act. 3, citing Gruskin Abstract, 4---6, 8, 11. 25-30, 10, 11.
22-23, 11, 11. 18-19, 14, 11. 21-28, and 17, 11. 6-20.)
3 Gruskin et al., WO 01/66695 Al, published Sept. 13, 2001 ("Gruskin").
4 Forgacs et al., US 8,241,905 B2, issued Aug. 14, 2012 ("Forgacs").
5 The Examiner identifies claim 2 in the statement of rejection (Rejection
No. 1), but claim 2 is not included in that rejection. (See Ans. 3.)
6 Boland et al., US 2004/0237822 Al, published Dec. 2, 2004 ("Boland").
7 Harmon et al., US 2005/0058629 Al, published March 17, 2005
("Harmon").
8 K.J.L. Burg et al., Minimally Invasive Tissue Engineering Composites and
Cell Printing, IEEE Engineering in Medicine and Biology, 84--91 (Sept./Oct.
2003) ("Burg").
9 M.L. Sabolinski et al., Cultured skin as a 'smart material' for healing
wounds: experience in venous ulcers, Biomaterials 17, 311-20 (1996)
("Sabolinski").
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Application 12/293,490
FF 2. Forgacs teaches "[a] variety of printing or dispensing devices," and
particularly 'jet-based cell printers" and "ink-jet technology." (Forgacs col.
4, 1. 38 and col. 14, 11. 31-33.) The Examiner finds that Forgacs teaches ink
jet printing of multiple layers of at least two different mammalian cell types
on a substrate, and printing the cells with collagen (i.e. a support
compound). (Final Act. 4, citing Forgacs col. 14, 11. 31-36, Example 2, and
claims 18-3 5.)
FF 3. The Examiner finds that Boland teaches a method of ink-jet printing
an array of viable cells, such as mammalian cells, onto a substrate, wherein
multiple cell types can be printed together. (Final Act. 5, citing Boland ,r,r 6,
33, 46-48, 60, and Examples.)
FF 4. The Examiner finds that Harmon teaches making artificial skin
composites comprising fibroblasts, keratinocytes, and melanocytes for
implantation, including for replacement of damaged tissue. (Final Act. 6,
citing Harmon Abstract and ,r,r 24, 186, 199,212,213,217,241,244,248,
251, and 253.)
DISCUSSION
We adopt the Examiner's findings, analysis, and conclusions,
including with regard to the scope and content of, and motivation to
combine, the prior art, as set forth in the Final Action and Answer. We
discern no error in the rejections of the claims as obvious.
Issue
Whether a preponderance of evidence of record supports the
Examiner's rejections under 35 U.S.C. § 103(a).
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Principles of Law
The test for obviousness is "what the combined teachings of the
references would have suggested to those of ordinary skill in the art" and not
"that the claimed invention must be expressly suggested in any one or all of
the references." In re Keller, 642 F.2d 413,425 (CCPA 1981) (citing cases).
An obviousness analysis "need not seek out precise teachings directed
to the specific subject matter of the challenged claim, for a court can take
account of the inferences and creative steps that a person of ordinary skill in
the art would employ." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,418
(2007).
Rejection No. 1
Analysis
We limit our consideration to claims 1 and 20 because the claims
subject to this rejection were not otherwise argued separately.
Examiner's Position
The Examiner concludes that
it would have been obvious to one of skill in the art at the time
of the instant invention to print fibroblasts and keratinocytes for
a skin graft in the printing method taught by F orgacs []. One
would have been motivated to do so because Forgacs [] teach[es]
the benefits of printing cell aggregates, such as increased cellular
concentrations and reduced time to print the cells .... One would
have had a reasonable expectation for success because Forgacs
[] teach[ es] successfully printing cell aggregates. In addition, it
is respectfully held that one of skill in the art, in recognizing the
success in printing different cell types, one would have been
motivated to expand the process to printing skin grafts with a
reasonable expectation for success.
(Final Act. 4, citing Forgacs col. 4, 11. 25--40, col. 5, 11. 3-15.)
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Application 12/293,490
We find that the Examiner has established a prima facie case of
obviousness based on the combination of Gruskin and Forgacs. (Final Act.
3--4.)
Appellants 'Arguments
Claim 1
We note that claim 1 is written in Jepson format ("the improvement
comprising"), and thus is an implied admission that the subject matter of the
preamble is the prior art work of another. (See MPEP § 2129.) That
construction is consistent with Appellants' reference to Boland in the
Specification (see Spec. 5, 11. 17-19) and the teachings of Boland (see
Boland ,r 6). We also note that, although claim 20 recites ink-jet printing,
the body of claim 1 only recites "printing." (Appeal Br. 12, 14.) However,
regardless of whether we interpret "printing" in claim 1 as limited to "ink-jet
printing," or as referring to any type of cellular printing, we nevertheless
agree with the Examiner that claim 1 would have been obvious.
Appellants argue that the combination of Gruskin and Forgacs "fails
to teach ink-jet printing of multiple layers of at least two different primary
mammalian cell types, such as the elected species of a combination of
keratinocytes, fibroblasts, and melanocytes." (Appeal Br. 6; see also Reply
Br. 2.) According to Appellants, Forgacs does not teach "'printing' of two
different cell types" or "ink-jet printing" as claimed, and "does not teach
successful ink-iet printing of keratinocytes, fibroblasts, and melanocytes."
(Appeal Br. 6-7.) Appellants also contend that the Examiner has not
explained how the "aggregates" printed by Forgacs would be translated into
a skin graft of Gruskin for in vivo application. (Id. at 6.)
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We are not persuaded. As explained by the Examiner, the rejection is
based on the combination of Gruskin's teaching of seeding ( e.g.,
keratinocytes and fibroblasts) (FF 1) and Forgacs's teaching of the
application of ink-jet printing to different cell types (FF 2). (Ans. 4.)
Forgacs teaches ink-jet printing of at least two different cell types, 10 and
there is no requirement that Forgacs alone teach "successful ink-;et printing
of keratinocytes, fibroblasts, and melanocytes." See Keller, 642 F.2d at 425.
The Examiner's reliance on Forgacs for teaching ink-jet printing of different
cell types, rather than the skin tissue cells as taught by Gruskin, also explains
why Forgacs's reference to cell "aggregates" does not diminish a conclusion
of obviousness. 11
Appellants also argue that Forgacs does not provide a motivation to
expand its process to printing skin grafts, and that there is no motivation to
combine Gruskin and Forgacs because they are "directed to different
methods." (Appeal Br. 6-7.) We are not persuaded. The Examiner points
to Forgacs's teaching of specific advantages to using ink-jet printing "[i]n
contrast to previously known methods of tissue engineering which are based
on seeding individual cells." (Ans. 4, citing Forgacs col. 4, 11. 25-26; see
also 11. 2 7--41.) The combination of Gruskin and F orgacs "is thus the
adaptation of an old idea or invention [Gruskin] using newer technology
[ink-jet printing] that is commonly available and understood in the art
10 "Many cell types may be used to form the bio-ink cell aggregates .... One
skilled in the art will thus readily be able to choose an appropriate cell
type( s) for the aggregates, based on the type of three-dimensional construct
to be printed." (Forgacs 6, 11. 55-56 and 1. 64--7, 1. 10.)
11 We also note that Appellants' Specification refers to "cell aggregates to be
printed according to the invention." (Spec. 6, 1. 31.)
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[Forgacs]." See Leapfrog Enters., Inc. v. Fisher-Price, Inc., 485 F.3d 1157,
1162 (2007).
Appellants also argue that there is no reasonable expectation of
success in using the methods of F orgacs to print skin grafts or to form a
seeded skin cell construct as taught by Gruskin. (Appeal Br. 6-7.) We are
not persuaded. Appellants' argument is premised on the contention that the
teachings of F orgacs are limited to depositing aggregates of Chinese hamster
ovary (CHO) cells transfected with N-cadherin. (Appeal Br. 7.) However,
in an obviousness analysis, "[ a ]11 the disclosures in a reference must be
evaluated, including nonpreferred embodiments, and a reference is not
limited to the disclosure of specific working examples." In re Mills, 470
F.2d 649, 651 (CCPA 1972) (internal citations omitted). Moreover, to the
extent Appellants are arguing that there would be no reasonable expectation
of success in physically combining Forgacs with Gruskin, that argument is
unavailing because the test for obviousness is "what the combined teachings
of the references would have suggested to those of ordinary skill in the art."
See Keller, 642 F.2d at 425. We do not find any persuasive evidence that
adapting ink-jet printing to skin grafts or skin tissue was beyond the level of
one of ordinary skill in the art. KSR, 550 U.S. at 421 ("A person of ordinary
skill is also a person of ordinary creativity, not an automaton."); In re
Sovish, 769 F.2d 738, 743 (Fed. Cir. 1985) (skill is presumed on the part of
one of ordinary skill in the art).
Claim 20
Appellants advance the same arguments as addressed above in
connection with the combination of Gruskin and F orgacs, and they are
unpersuasive for the reasons set forth above. (Appeal Br. 8.) Appellants
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also argue that there is no teaching or suggestion "as to the particular ink-jet
printing steps as recited in independent claim 20." (Id.) We disagree.
Forgacs teaches ink-jet printing and Gruskin teaches a method of providing a
layer of fibroblasts followed by "associating another layer including
keratinocytes with the layer including the ... fibroblasts." (See, e.g.,
Gruskin 4, 11. 20-27 and 8, 11. 24--29.)
Accordingly, for the reasons of record and as set forth above, we
affirm the rejection of claims 1 and 20 for obviousness in view of Gruskin
and Forgacs. Claims 4, 12, 17, 19, 21 and 22 were not argued separately and
fall with claims 1 and 20.
Rejection No. 2
Analysis
We limit our consideration to claim 1 because the claims subject to
this rejection were not argued separately.
Examiner's Position
The Examiner concluded that
it would have been obvious to one of skill in the art at the
time of the instant invention to print different cell types, and
specifically to print fibroblasts, keratinocytes, and melanocytes
to make skin grafts for implantation in vivo to, e.g., promote
wound healing, utilizing the printing method of Boland[].
One would have been motivated to do so because Burg []
teach[es] that ink-jet printing is inexpensive, repeatable, flexible,
easy to use, and provides many advantages over previously
developed methods of constructing cellular patterns, that an
injectable composite may be successfully used, and that printing
technologies will minimize preparation times . . . . One would
have been motivated to utilize skin and particularly the
fibroblast, keratinocyte, and melanocyte components of skin, in
order to promote healing of chronic wounds which have trouble
healing ....
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One would have had a reasonable expectation for success
because Boland [] teach[ es] successfully printing cells, and
successfully printing multiple cell types (see Examples) ... In
addition, it was well known at the time of the invention that
fibroblasts, keratinocytes, and melanocytes were components of
skin.
(Final Act. 7, citing Burg 90, cols. 1 and 2, col. 2, ,r,r 2-3.)
We find that the Examiner has established a prima facie case of
obviousness. (Final Act. 5-8.) We adopt our construction of claim 1 as set
forth above.
Appellants 'Arguments
Appellants contest the Examiner's reliance on Boland because it does
not teach the elected species, and because the only examples provided in
Boland are of bacterial cells and certain mammalian cell lines. (Appeal Br.
8-9.) Appellants also argue that Boland teaches away from printing
multiple cell types by noting surprise that the cells they had used remained
viable after the printing step. (Id. at 9; see also Reply 3.)
We are not persuaded. The Examiner relies on Harmon for teaching
the elected species (FF 4 ), and the teachings of Boland are not limited to its
examples. See Mills, 4 70 F .2d at 651. Boland does not teach away because
it does not "criticize, discredit, or otherwise discourage" printing multiple
cell types (FF 3). See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Moreover, obviousness does not require that the asserted combination of
teachings render a result that is "predictable" (Appeal Br. 9); rather, all that
is required is a reasonable expectation of success.
Appellants also contest the Examiner's reliance on Harmon because it
"merely makes mention of, in widely scattered locations, fibroblasts,
melanocytes, and keratinocytes." (Appeal Br. 9.) Appellants also argue that
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Hannon "does not suggest the use of ink-jet printing to create any type of
tissue, much less skin tissue." (Id.) We are not persuaded. A reference is
considered for all it discloses, and the Examiner relies on Boland for
teaching ink-jet printing. (FF 3.)
Appellants argue that "there is no teaching, suggestion, or reasonable
expectation of success that the cells of Harmon could be ink-jet printed by
the methods described in Boland," and that "the unpredictability of the art
... provides evidence against such a finding." (Appeal Br. 9--10.) We are
not persuaded. Harmon and Boland teach and suggest the limitations of
claim 1, and "obviousness cannot be avoided simply by a showing of some
degree of unpredictability in the art so long as there was a reasonable
probability of success." Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364
(Fed. Cir. 2007).
Appellants also contest the Examiner's reliance on Burg and
Sabolinski. (Appeal Br. 10; Reply Br. 3.) However, for the rejection of
claim 1, Burg is relied upon to show further motivation to use ink-jet
printing, and as further evidence of a reasonable expectation of success, as
also established by Boland and Harmon. (Final Act. 7 .) Sabolinski is relied
on for dependent claim( s) rather than claim 1. (Id. at 6-7.)
Accordingly, for the reasons of record and as set forth above, we
affirm the rejection of claim 1 (Rejection No. 2). Claims 2, 4, 12-14, and
1 7-19 were not argued separately and fall with claim 1.
Conclusion of Law
A preponderance of evidence of record supports the Examiner's
rejections of claims 1, 2, 4, 12-14, and 17-22 under 35 U.S.C. § 103(a).
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SUMMARY
We affirm the rejections of all claims on appeal.
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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