Ex Parte Fogher et al

Patent Trial and Appeal Board

Nov 22, 2016

12377085 (P.T.A.B. Nov. 22, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/377,085 02/18/2009
23117 7590 11/25/2016
NIXON & V ANDERHYE, PC
901 NORTH GLEBE ROAD, 11 TH FLOOR
ARLINGTON, VA 22203
FIRST NAMED INVENTOR
Corrado Fogher
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.
GRT/4161-51 2534
EXAMINER
WORLEY, CATHY KINGDON
ART UNIT PAPER NUMBER
1662
NOTIFICATION DATE DELIVERY MODE
11/25/2016 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):
PTOMAIL@nixonvan.com
pair_nixon@firsttofile.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CORRADO FOGHER, SERENA REGGI, and
KIRIL PERF ANOV. 1
Appeal2015-006080
Application 12/377,085
Technology Center 1600
Before DEMETRA J. MILLS, JEFFERY N. FREDMAN, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) of the Examiner's Final
Rejection involving claims 9--17 to a genetically modified plant which have
been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
The present invention is directed to plants transformed to produce
Apolipoproteins in oligomeric form. Spec. 1. The novel proteins are
1 Appellants identify the Real Party in Interest as Plantechno S.r.l. Br. 3.
Appeal2015-006080
Application 12/377,085
muteins of human ApoA-1 and exhibit increased stability and capacity to
transport cholesterol. Id.
Claims 9-17 are on appeal. Claim 9 is illustrative and reads as
follows:
9. A genetically transformed plant with one or more
expression vectors comprising a seed-specific expression
cassette and a nucleotide sequence encoding a mutein of human
apolipoprotein (Apo) A-1, expressing in the seed's storage
tissue one or more of said muteins, and forming oligomers
comprising three or more monomers, in an essentially
oligomeric form, said one or more muteins characterised in that
they show in their oligomeric forms biological activities equal
to or higher than the activities shown by apolipoprotein (Apo)
A-1 Milano in its dimeric form in the following tests:
a') measurement of the reverse cholesterol transport capacity
evaluated by calculation of the association kinetics of equal
quantities of said oligomer, and of the said dimer of Apo A-1
Milano with dimyristoylphosphatidylcholine (DMPC); and
b ') measurement of the plasma half life of said oligomer by a
plasma half life test in comparison to a calibration curve
obtained performing the same test with the purified Apo A-1
Milano dimer.
The claims stand rejected as follows:
Claims 9-17 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over Moloney2 in view of Zhu3.
2 Moloney at al., US 2005/0172359 Al, published Aug. 4, 2005
("Moloney").
3 Zhu et al., Cysteine mutants of human apolipoprotein A-1: a study of
secondary structural and functional properties, 46 JOL. LIPID RES. 1303
(2005) ("Zhu").
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Appeal2015-006080
Application 12/377,085
THE REJECTION UNDER 35 U.S.C. § 103(a)
Issue
In rejecting the pending claims as obvious, the Examiner finds that
Moloney teaches expression of apolipoproteins in plants. Final Act. 4. The
Examiner finds that Moloney specifically teaches the Apo A-1 "Milano" and
"Paris" muteins. Id. The Examiner finds that expression of the "Milano"
mutein would inherently lead to dimers that have equal activities shown by
Apo A-1 Milano dimers. Id. The Examiner goes on to find that Zhu teaches
seven different muteins of Apo A-1, each having a cysteine substitute ad a
defined position in one of the alpha helices of the protein. Final Act. 4. The
Examiner finds that each of these mutations form dimer and oligomers and
possessed different characteristics regarding association with lipids. Id. The
Examiner concludes that
[a ]t the time the invention was made, it would have been
obvious and \~1ithin the scope of one of ordinar; skill in the art
to generate double mutants that would comprise the cysteine
substitution found in Apo A-1 "Milano" and also the cysteine
substitution found in Apo A-1 "Paris". One would have been
motivated to do so, because beneficial effects have been
observed with each of these mutations, and it would have been
obvious to combine the mutations to achieve the benefits of
both mutations in one mutein. Introducing two cysteines would
result in formation of oligomers with more than two monomer
subunits, because additional cysteines would be available for
forming di-sulfide bonds.
Final Act. 4--5.
Appellants contend that the cited references teach muteins with only
one free cysteine and that they are not capable of forming oligomers.
Appeal Br. 8. Appellants argue that the muteins disclosed in Moloney
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Appeal2015-006080
Application 12/377,085
cannot reach the storage organs of the plant and cannot form oligomers
without further processing. Appeal Br. 9. Appellants point out that Zhu only
discloses the formation of dimers and does not teach the formation of
oligomers. Final Act. 9--10. Appellants go on to argue that the Examiner
failed to consider Appellants' evidence of unexpected results. Appeal Br.
12-13. Appellants also argue that the Examiner has failed to establish that
one skilled in the art would have a reasonable expectation of success in
producing oligomeric forms of Apo A-1 muteins. Appeal Br. 8-9.
The issue with respect to this rejection is whether the Examiner has
established by a preponderance of the evidence that claims 9--17 would have
been obvious over Moloney combined with Zhu as defined by 35 U.S.C.
§ 103(a).
Principles of Law
"Where claimed subject matter has been rejected as obvious in view
of a combination of prior art references, a proper analysis under § 103
requires, inter alia, consideration of two factors: ( 1) whether the prior art
would have suggested to those of ordinary skill in the art that they should
make the claimed composition or device, or carry out the claimed process;
and (2) whether the prior art would also have revealed that in so making or
carrying out, those of ordinary skill would have had a reasonable expectation
of success. Both the suggestion and the reasonable expectation of success
must be founded in the prior art, not in the applicant's disclosure." In re
Vaeck, 947 F.2d 488, 493 (Fed. Cir. 1991) (citation omitted).
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Appeal2015-006080
Application 12/377,085
Analysis
We agree with Appellants that the Examiner has failed to put forth
persuasive evidence that one skilled in the art would have a reasonable
expectation of success in combining the teachings of the references. Appeal
Br. 8-9, Reply Br. 5-7. As Appellants point out, the Examiner has failed to
explain why introducing two cysteine substitution at the locations cited by
the Examiner would produce an oligomer as opposed to forming an intra-
chain disulfide bond. Reply Br. 6-7. Thus one skilled in the art would not
have a reasonable expectation of success in producing oligomers as required
by the claims.
The Examiner argues that the introduction of two mutations into the
same Apo A-1 mutein would have been prima facie obvious since the prior
art taught that each mutation would be useful for the same purpose. Ans. 5-
6. While the Examiner has correctly cited the general proposition regarding
combining two compositions with the same known properties, we find the
per se argument unpersuasive in the present case. As Appellants point out,
in the present case,
[O]ne of ordinary skill would have basic knowledge from
protein engineering and known that mutant residues may
interact when introduced into the same protein AND their
beneficial effects may not be additive, especially where Zhu
showed residues R151C (Apo A-1 Milano) and RI 73C (Apo A-
l Paris) occupy similar positions in helix 5 and helix 6,
respectively (see Figure l's legend at page 1305). Under these
circumstances, one of ordinary skill would not have had a
reasonable expectation of whether the substituted cysteines
interact with each other OR their effects on Apo A-1 activity
are additive.
Reply Br. 4
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Appeal2015-006080
Application 12/377,085
Conclusion of Law
We conclude that the Examiner has failed to establish by a
preponderance of the evidence that claims 9--17 would have been obvious
over Moloney combined with Zhu under 35 U.S.C. § 103(a).
DECISION
We reverse the rejection under 35 U.S.C. § 103(a).
REVERSED
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