Ex Parte Kerr-Conte et al

Patent Trial and Appeal Board

Apr 20, 2017

13101237 (P.T.A.B. Apr. 20, 2017)

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.
13/101,237 05/05/2011 Julie Kerr-Conte 11-239 4583
34704 7590 04/21/2017 EXAMINERBACHMAN & LAPOINTE, P.C.
900 CHAPEL STREET PYLA, EVELYN Y
SUITE 1201
NEW HAVEN, CT 06510 ART UNIT PAPER NUMBER
1651
MAIL DATE DELIVERY MODE
04/21/2017 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 JULIE KERR-CONTE and BRUNO DELORME1
Appeal 2016-006234
Application 13/101,237
Technology Center 1600
Before DEMETRA J. MILLS, ERIC B. GRIMES,
and JOHN E. SCHNEIDER, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to methods
for preserving insulin secreting cells which have been rejected as obvious.
We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
The invention relates to transplantation of pancreatic islets or
Langerhan’s islets to treat such pancreatic disorders as diabetes. Spec. 12.
1 Appellants identify the Real Parties in Interest as Maco Pharm, Universite
Du Droit Et De La Sante De Lille 2, and Centre Hospitalier Regional
Universitaire De Lille. Appeal Br. 2.
Appeal 2016-006234
Application 13/101,237
The invention involves a method for preserving insulin-secreting cells for up
to 7 days while maintaining their functionality. Spec. 28 and 29.
Claims 1,3, 6—16, and 19-22 are on appeal. Claims 1 and 16 are
representative of the rejected claims and read as follows:
1. A method for preserving a preparation of pancreatic islets
and proteolytic enzymes including:
placing said preparation of pancreatic islets and proteolytic
enzymes in contact with a biological medium including a
nutritive product including albumin, wherein the biological
medium further includes polyethylene glycol, said polyethylene
glycol being present in an amount as high as 1% by
weight/volume, and further including a substrate for said
enzymes, said substrate including a peptone or a mixture of
peptones in sufficient quantity to preserve insulin-secreting cells;
wherein said peptone is rich in amino acids having at least one of
a carboxy-terminal group, a long aromatic side chain and a
hydrophobic side chain, wherein said peptone is rich in leucine,
phenylalanine, tyrosine and tryptophan, the cumulative content
of these four amino acids being greater than 150 mg/g, wherein
an endotoxin level of said peptone is lower than 200 EU/g.
16. A drug for treating pancreatic diseases, including a
composition including (a) a preparation of insulin-secreting
cells and (b) biological medium with albumin and one of a
peptone and a mixture of peptones; wherein said peptone is rich
in amino acids having at least one of a carboxy-terminal group,
a long aromatic side chain and a hydrophobic side chain;
wherein said biological medium further comprises polyethylene
glycol, said polyethylene glycol being present in an amount as
high as 1% by weight/volume.
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Appeal 2016-006234
Application 13/101,237
Claims 1, 3, 6—16, and 19-22 stand rejected under 35 U.S.C. § 103(a)
as unpatentable over Pattou2 in view of Fong,3 Newsholme,4 Giraud,5 and
Lee6 as evidenced by BD Bionutrients7 and BD Pharmaceutical.8
DISCUSSION
Issue
The issue is whether a preponderance of evidence supports the
Examiner’s finding that claims 1,3, 6—16, and 19-22 would have been
obvious over Pattou combined with Fong, Newsholme, Giraud, and Lee.
The Examiner finds that Pattou teaches a method of preserving islet
cells for up to 72 hours. Final Act. 6. While the Examiner finds that Pattou
teaches the same general steps as recited in the instant claims, Pattou does
not disclose the claimed amount of albumin nor does Pattou teach the use of
peptones containing leucine, phenylalanine, tyrosine, and tryptophan or
polyethylene glycol (“PEG”). Final Act. 7. The Examiner finds that Fong
2 Pattou et al., US 2009/0286315 Al, published Nov. 19, 2009 (“Pattou”).
3 Fong et al., Hormones and Factors that Stimulate Growth of a Rat Islet
Tumor Cell Line in Serum-Free Medium, 30 Diabetes 1022 (1981) (“Fong”).
4 Newsholme et al., New insights into amino acid metabolism, f-cell
function and diabetes, 108 Clinical Sci. 185 (2005) (“Newsholme”).
5 Giraud et al., A New Preservation Solution (SCOT 15) Improves the Islet
Isolation Process From Pancreata of Non-Heart Beating Donors: A Murine
Model, 41 Transplant. Proc. 3293 (2009) (“Giraud”).
6 Lee et al., A New Strategy Toward Improving Immunoprotection in Cell
Therapy for Diabetes Mellitus: Long-Functioning PEGylated Islets In Vivo,
12 Tissue Engr. 615 (2006) (“Lee”).
7 BD Biosciences, BD Bionutrients Technical Manual: Advanced
Bioprocessing (3rd ed. 2006) (“BD Bionutrients”).
8 BD Biosciences, BD Biopharmaceutical Production: Bionutrient Technical
Manual (2nd ed.) (“BD Biopharmaceuticals”).
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Application 13/101,237
teaches a method of stimulating growth of islets using a medium containing
peptones. Final Act. 7—8. The Examiner finds that Newsholme teaches that
the amino acids leucine and phenylalanine have a positive effect on insulin
secretion in the presence of protein hydrolysates. Final Act. 8. The
Examiner finds that it would have been a matter of routine experimentation
to find the optimum amounts of the amino acids recited in the claims. Final
Act. 9—11. The Examiner finds that the use of PEG to preserve islets is
taught by Giraud and Lee. Final Act. 12.
The Examiner concludes that
given that the intention of Pattou is to preserve insulin
producing pancreatic islet cells in order to prepare them for
subsequent transplantation and given that Giraud teaches the
pancreatic islet cell preservation solution comprising 1.5%
polyethylene glycol performs better than UW solution (i.e.
University of Wisconsin) or a CMRL 1066 culture solution
supplemented with 1% BSA (bovine serum albumin) and the
PEG supplement has immunoprotective effects, improves islet
yield and increases islet survival in the absence of an
immunosuppressant and given that Lee discloses that
immunoprotection of islets cells can be provided by modifying
the islet cell surface by adding the 0.25% PEG suspension to
the islet cells, it would have been obvious to one having
ordinary skill in the art at the time of the invention to combine
the teachings of Giraud and Lee with those of Pattou, Fong and
Newsholme, to further include polyethylene glycol at a
concentration of 0.25% wt/vol in the islet cell culture medium,
for the predictable result of successfully improving islet cell
yield and viability in the method of Pattou, thus meeting the
limitations of claim 1.
Final Act. 12—13.
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Application 13/101,237
Appellants contend that Pattou does not teach the use of a peptone
supplement or PEG in the medium used to preserve the islets. Appeal Br.
10. Appellants argue that none of the references teach the presence of a
substrate for proteolytic enzymes as called for in the claims. Id. Appellants
argue that Newsholme teaches away from the present invention in that it is
directed to stimulating insulin production and not preserving islets. Appeal
Br. 11. Appellants argue that Fong and Newsholme would lead one skilled
in the art to add peptones but would not lead one skilled in the art to use
peptone containing the specific amino acids recited in the claims nor in the
claimed amounts. Appeal Br. 11—12. Appellants contend that the concept of
routine optimization does not apply to the present facts given that there is no
overlap of the ranges nor are the ranges close. Appeal Br. 12—13.
Appellants also argue that nothing in the references teaches the use of the
claimed peptides as a substrate for the proteolytic enzymes and that one
skilled in the art would not seek to optimize the concentration of the amino
acids to help preserve the islets. Appeal Br. 14. Appellants also contend
that nothing in the references teaches the level of endotoxin recited in the
claims. Appeal Br. 14.
Findings of Fact
We adopt as our own the Examiner’s findings and analysis. The
following findings are included for emphasis and reference convenience.
FF1. Pattou discloses a
Process for preserving insulin secreting cells intended to be
transplanted, including the following steps: introducing an
initial volume of culture medium and insulin-secreting cells
into a culture container, providing a culture medium source, and
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Application 13/101,237
replacing, at time intervals below 8 hours, the culture medium
in the culture container with culture medium from the source so
as to renew the culture medium contained in the container
Pattou, Abstract.
FF2. The process of Pattou enables “a survival rate of above 60% to
be obtained for up to 72 hours, and the functionality of the islets, i.e. their
capacity to produce insulin once re-implanted in the recipient to be
maintained.” Pattou 112.
FF3. Pattou teaches the use of a medium for maintaining the islets
which contains albumin. Pattou 139.
FF4. Fong investigated the long term maintenance of insulin
producing cells using serum free media including media supplemented with
peptones. Fong, 1023, right col.
FF5. Fong teaches that “[pjroteose peptone (a protein hydrolysate at a
concentration of 0.5 mg/ml). . . stimulated growth of the islet cell line in
serum-free medium.” Fong, 1023, right col. under RESULTS.
FF6. Fong teaches that “[pjroteose peptone enhances [islet tumor cell
line] RIN-r growth, alone and in the presence of other factors. ... Of
interest is an effect of proteose peptone factors on cultures of normal islet
cells.” Fong, 1027, right col.
FF7. The proteose peptone in Fong came from Difco. Fong, 1023,
left col.
FF8. The Examiner finds that DIFCO is synonymous with BD Difco,
Becton Dickinson. Final Act. 8.
FF9. BD Bionutrients discloses that BD proteose peptone, Bacto
contains 5.7% leucine, 3.6% phenylalanine, 1.8% tyrosine, and 0.1%
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Application 13/101,237
tryptophan, which the Examiner calculates to be equivalent to 112mg/g of
these four amino acids. BD Bionutrients, 42-43, Final Act. 8—9.
FF10. BD Pharmaceuticals teaches that proteose peptone No. 3 Bacto
contains 20 EU/g of endotoxin. BD Biopharmaceutical, 7.
FF11. Newsholme teaches that leucine and phenylalanine increase
insulin production. Newsholme, 185.
FF12. Giraud teaches the use of PEG in media to preserve islets.
Giraud, 3293.
FF13. Fee teaches the use of PEG to improve the functionality and
survival time of transplanted islets. Fee, 615, Abstract.
Principles of Law
The test of obviousness is “whether the teachings of the prior art,
taken as a whole, would have made obvious the claimed invention.” In re
Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991).
A reference may be said to teach away when a person of
ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference, or
would be led in a direction divergent from the path that was
taken by the applicant. The degree of teaching away will of
course depend on the particular facts; in general, a reference
will teach away if it suggests that the line of development
flowing from the reference’s disclosure is unlikely to be
productive of the result sought by the applicant.
In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
The law is replete with cases in which the difference between
the claimed invention and the prior art is some range or other
variable within the claims. These cases have consistently held
that in such a situation, the applicant must show that the
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Application 13/101,237
particular range is critical, generally by showing that the
claimed range achieves unexpected results relative to the prior
art range.
In re Woodruff, 919 F. 2d 1575, 1578 (Fed. Cir. 1990) (citations omitted,
emphasis in original).
Analysis
We agree with the Examiner that the subject matter of claims 1 and 16
would have been obvious to one skilled in the art at the time the invention
was made. Pattou and Fong both teach methods for preserving islets. FF1
and 4. Fong discloses the use of peptones containing leucine, phenylalanine,
tyrosine, and tryptophan to promote the growth of islets. FF4—9. Giraud
and Lee teach the use of PEG to preserve islets. FF12 and 13. We agree
with the Examiner that it would have been obvious to one skilled in the art to
use the peptones and PEG of Fong, Giraud, and Lee in the islet preservation
method of Pattou to create the claimed method and composition. Final Act.
12-13.
Appellants contend that Pattou does not teach the use of a peptone
supplement nor the use of PEG in the amounts recited in the claims. Appeal
Br. 10. While we agree with Appellants regarding the teachings of Pattou,
Fong, Newsholme, Giraud, and Lee provide the necessary teachings
regarding these claim elements. FF4—13.
Appellants argue that none of the references teach the presence of a
substrate for the proteolytic enzymes. Appeal Br. 10. We are unpersuaded.
As the Examiner points out, Fong teaches supplementation of the islet
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Application 13/101,237
culture with peptone containing the listed amino acids, thus the peptone
disclosed in Fong contains the substrate for the enzymes. Ans. 17.
Appellants also argue that Fong and Newsholme would only lead one
skilled in the art to add leucine and phenylalanine and not the claimed
combination of four amino acids. Again, we are not persuaded. Fong
discloses the use of peptones from Becton Dickinson which contain the four
amino acids. FF7—9.
Appellants contend that Newsholme teaches away from the present
invention in that Newsholme is directed to increasing insulin secretion and
not islet preservation. Appeal Br. 11. We are not persuaded. While
Appellants argue that Fong and Newsholme would lead one skilled in the art
away from the claimed invention, Appellants point to no specific teaching in
either reference which would lead away from using peptones to preserve
islets. In fact, Fong specifically teaches the use of peptones to preserve
islets. FF4—6.
We are unpersuaded by Appellants’ arguments that the references do
not teach the specific amounts of amino acids nor would one achieve that
claimed amount through routine optimization. While we agree with
Appellants that there is no overlap between the claimed range and that
taught by the prior art, we agree with the Examiner that, based on the
teachings of Fong and Newsholme, one skilled in the art would have been
motivated to optimize the amounts of the recited amino acids. Ans. 17—18.
In addition, Appellants have pointed to nothing in the record showing that
the claimed amounts are critical to the invention by showing unexpected
results. In re Woodruff, 919 F.2d at 1578.
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Finally, with respect to Appellants’ arguments regarding the amount
of endotoxin in the medium, we agree with the Examiner that it would have
been obvious to one skilled in the art from the teachings of Fong and the BD
references to use a peptone (such as the commercially available proteose
peptone No. 3 Bacto) having a low level of endotoxin. Ans. 18.
Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner’s finding that claims 1 and 16 would have been obvious over
Pattou combined with Fong, Newsholme, Giraud, and Lee under 35 U.S.C.
§ 103(a).
Claims 3, 6—15, and 19-22 have not been argued separately and
therefore fall with claims 1 and 16. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We affirm the rejection under 35 U.S.C. § 103(a).
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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