Ex Parte Cicciarelli et al

Patent Trial and Appeal Board

Nov 28, 2016

13567064 (P.T.A.B. Nov. 28, 2016)

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.
13/567,064 08/05/2012 James C. Cicciarelli NITF-001-CON 9557
89633 7590 11/30/2016
Brian Pangrle
Pangrle Patent, Brand & Design Law, P.C.
3500 W Olive Ave
3rd Floor
Burbank, CA 91505
EXAMINER
WHITEMAN, BRIAN A
ART UNIT PAPER NUMBER
1674
NOTIFICATION DATE DELIVERY MODE
11/30/2016 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JAMES C. CICCIARELLI,
NORIYUKI KASAHARA, and CHRISTOPHER R. LOGG1
Appeal 2014-009731
Application 13/567,064
Technology Center 1600
Before FRANCISCO C. PRATS, ULRIKE W. JENKS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to methods of
making a set of lentivirus vectors that function as negative modulators of an
immune response involving the Human Leukocyte Antigens (HLA). The
Examiner rejected the claims for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.
1 Appellants state that the “real party in interest is The National Institute of
Transplantation Foundation.” App. Br. 2.
Appeal 2014-009828
Application 13/615,183
STATEMENT OF THE CASE
The sole rejection before us for review is the Examiner’s rejection of
claims 1, 2, 5, 6, 9-16, and 18—20, under 35 U.S.C. § 103(a), for
obviousness over Rossi,2 Radcliffe,3 and Uchida.4 Final Action 3—5.5
Claim 1, the sole independent claim on appeal,6 illustrates the
appealed subject matter and reads as follows (App. Br. 21):
1. A method of making a kit that comprises a set of lentivirus
vectors for altering allogeneic human cells for a human recipient, the
method comprising:
forming the set of lentivirus vectors wherein each of
the lentivirus vectors expresses a sequence targeting a consensus
conserved nucleic acid sequence, which when expressed in cells,
functions as a negative modulator for nucleic acid encoding a domain
having a mismatch in an HLA protein and wherein the set of lentivirus
vectors comprises individual lentivirus vectors that correspond to
individual HLA mismatches for a set of HLA mismatches that consist
of HLA Class I mismatches and at least one HLA Class II mismatch;
wherein the kit is for treatment of human cells by an
appropriate subset of the set of lentivirus vectors based on
determining a subset of the set of HLA mismatches between a human
2 John Rossi et al., US 2005/0227940 A1 (published Oct. 13, 2005).
3 Philippa Radcliffe et al., US 2005/0106559 Al (published May 19, 2005).
4 Nobuko Uchida et al., U.S. Patent No. 5,928,638 (issued Jul. 27, 1999).
5 The Final Action also included a rejection under 35 U.S.C. § 112, first
paragraph (Final Action 2), and an obviousness rejection under § 103(a)
over a different combination of references (id. at 7—9). Those rejections
have been withdrawn. See Advisory Action (entered October 2, 2013); see
also Ans. 2.
6 Appellants contend that claim 16 is an independent claim. App. Br. 14—15.
As is evident, however, claim 16 recites “[a] subset of the lentivirus vectors
of the kit of claim 1” (id. at 23), and, therefore is not an independent claim.
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Application 13/615,183
donor and a human recipient or between human cells and a human
recipient.
OBVIOUSNESS
The Examiner’s Position
The Examiner cited Rossi as describing a process in which one or
more expression cassettes encoding an RNAi [interfering RNA] molecule
corresponding to a gene encoding a MHC class I gene are introduced into a
cell, “wherein the RNAi molecule is expressed and initiates RNA
interference of expression of the MHC gene, thereby down-regulating
expression of the MHC gene and disrupting antigen presentation (page 15).”
Final Action 4. The Examiner noted Rossi’s disclosure that “siRNA [small
interfering RNA] can be delivered using a viral vector selected from
retroviral and lentiviral vectors (page 8).” Id.
The Examiner cited Uchida as disclosing “the routine method steps set
forth in instant claims 6—10 and 12—15. For example see columns 1—7 and
16—24.” Id. (citing In re Alter, 220 F.2d 454, 456 (CCPA 1955) (“Where the
general conditions of a claim are disclosed in the prior art, it is not inventive
to discover optimum or workable ranges by routine experimentation.”)).
The Examiner cited Radcliffe for its disclosure of “making a library of
lentiviral vectors (claim 59).” Final Action 4.
The Examiner concluded that an ordinary artisan would have
considered it prima facie obvious “to combine the teaching of Rossi taken
with Uchida et al. and Radcliffe et al., namely to use routine steps for
making a composition comprising a set of lentiviral vectors as set forth in
claimed invention.” Id. at 5.
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Application 13/615,183
The Examiner reasoned that an ordinary artisan “would have been
motivated to combine the teaching[s] to prepare the composition for
delivery] to an animal or to determine which dosage unit form is the most
effective for reducing expression of an HLA protein.” Id. (citing KSR Int’l
Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (“The combination of familiar
elements according to known methods is likely to be obvious when it does
no more than yield predictable results.”)).
The Examiner further reasoned that an ordinary artisan “would have
been motivated to make a kit comprising a set of lentiviral vectors to save
time from having to make another vector each time a different HLA
mismatch is required.” Id.
Analysis
In proceedings before the Patent and Trademark Office,
the Examiner bears the burden of establishing a prima facie
case of obviousness based upon the prior art. [The Examiner]
can satisfy this burden only by showing some objective
teaching in the prior art or that knowledge generally available to
one of ordinary skill in the art would lead that individual to
combine the relevant teachings of the references.
In reFritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992) (citations and internal
quotations omitted, bracketed material in original).
For a number of reasons, we agree with Appellants that the Examiner
has not established a prima facie case of obviousness as to Appellants’ claim
1, the sole independent claim on appeal.
As our reviewing court has explained, “section 103 requires a fact­
intensive comparison of the claimed process with the prior art rather than the
mechanical application of one or another per se rule.” In re Ochiai, 71 F.3d
1565, 1571 (Fed. Cir. 1995); see also id. at 1572 (“[RJeliance on per se rules
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of obviousness is legally incorrect and must cease.”); see also KSR, 550 U.S.
at 418 (“[R]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
with some rational underpinning to support the legal conclusion of
obviousness.”).
Among the required findings of fact, the Supreme Court reaffirmed in
KSR that the “the scope and content of the prior art are to be determined . . .
[and] differences between the prior art and the claims at issue are to be
ascertained.” KSR, 550 U.S. at 406 (quoting Graham v. John Deere Co. of
Kansas City, 383 U.S. 1, 17—18 (1966)).
As noted above, the Examiner provided a summary of the disclosures
in the cited prior art references. The Examiner did not, however, explain
specifically which disclosures in the prior art correspond to which features
recited in the claims. Nor did the Examiner identify with any degree of
particularity the differences between the invention recited in independent
claim 1 and the cited prior art. Because the Examiner did not, as required,
make specific findings as to the differences between the claims and the prior
art, the Examiner did not make clear, specifically, what particular
modifications to Rossi’s process must be made to arrive at the process
recited in claim 1, and why the prior art would have suggested those
modifications.
To that end, although the Supreme Court has emphasized “an
expansive and flexible approach” to the obviousness question, KSR, 550
U.S. at 415, the Court, nonetheless, also has reaffirmed the importance of
determining “whether there was an apparent reason to combine the known
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elements in the fashion claimed by the patent at issue.” Id. at 418 (emphasis
added).
Ultimately, therefore, “[i]n determining whether obviousness is
established by combining the teachings of the prior art, the test is what the
combined teachings of the references would have suggested to those of
ordinary skill in the art.” In re GPACInc., 57 F.3d 1573, 1581 (Fed. Cir.
1995) (internal quotations omitted).
In addition to not expressly making the specific findings of fact,
discussed above, critical to a conclusion of prima facie obviousness, we
agree with Appellants that the Examiner has not explained persuasively why
the cited references would have suggested the process recited in Appellants’
claim 1.
Claim 1 recites a method of making a kit composed of a set of
lentivirus vectors for altering allogeneic human cells for a human recipient.
App. Br. 21. Claim 1 requires its practitioner to form a set of lentivirus
vectors, with each of the lentivirus vectors expressing a sequence targeting a
consensus conserved nucleic acid sequence. Id. When present in cells, the
expressed sequences must function as negative modulators for nucleic acids
encoding a domain having a mismatch in an HLA protein. Id.
In particular, claim 1 requires the set/library of vectors to include
individual lentivirus vectors that correspond to a set of HLA mismatches that
“consist of HLA Class I mismatches and at least one HLA Class II
mismatch.” Id. As intimated in the last “wherein” clause of claim 1, the kit
may be used to address HLA mismatches between a human cell donor and a
recipient, by inhibiting the immune response to the mismatched HLA
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antigens. Id.', see also Spec. ]Hf 4—28 (turning off/inhibiting HLA immune
response useful for avoiding graft rejection in variety of tissues).
Turning to the cited prior art, Rossi discloses “a method for
amplifying expression of double-stranded RNA, preferably RNAi, in a cell,
preferably a mammalian cell. The method comprises generally introducing a
plurality of expression cassettes encoding double-stranded RNA, including
siRNA or shRNA.” Rossi 122; see also id. at p. 14 (claim 1). Rossi further
discloses:
The method preferably comprises introducing the expression
vehicles into the cell together as a single unit, and more
preferably as a RNAi-expressing concatamer, preferably a
siRNA- or shRNA-expressing (collectively si/shRNA [short
hairpin RNA]) concatamer, which is more preferably in the
form of an expression vector, comprising a plurality of
promoter RNAi (si/shRNA) expression cassettes, one or more
of which express RNAi (si/shRNA).
Id.
Like the library recited in Appellants’ claim 1, as the Examiner found,
Rossi discloses that its vector may be used to down-regulate expression of
HLA genes. Id. 132 (“[Interfering with expression of MHC class I genes
using siRNA homologous with a sequence conserved in most classical
polymorphic HLA-A, -B and -C loci offers a mechanism to help prevent
rejection of an allogeneic graft or cells that express immunogenic vector-
encoded transgenes.”); see also id. atp. 15 (claim 13).
Rossi also discloses that its vector can be configured to target multiple
HLA genes:
Additional changes can be envisioned to further improve
the efficacy of the siRNA vector, such as using enhancer
elements, alternative Pol III promoters, alternative promoters,
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and a combination of siRNAs directed to different regions of the
HLA genes and/or targeting multiple essential components of
antigen processing and MHC (class I and II) expression.
Id. 172 (emphasis added).
The Examiner contends, apparently in view of these teachings, that an
ordinary artisan “would have been motivated to make a kit comprising a set
of lentiviral vectors to save time from having to make another vector each
time a different HLA mismatch is required.” Final Action 5; see also Ans.
5-7.
As seen above, however, Rossi discloses configuring its single vector
to target multiple HLA mismatches. Rossi 172. The Examiner does not
explain with any degree of particularity how preparing a library of vectors,
such as is disclosed in Radcliffe, from which suitable candidates must be
chosen, would save time, as compared to Rossi’s use of a single vector that
already contains sequences that address multiple potential HLA mismatches.
The Examiner argues instead:
One of ordinary skill in the art would have been motivated to
make a library of separate vectors instead of a library of vectors
comprising siRNA targeting multiple HLA protein mismatches
so one ordinary skill in the art could pick and choose which
HLA protein(s) need to be targeted. This is a simple
substitution of one known element for another to obtain
predictable results or obvious to try choosing from a finite
number of identified predictable solutions with a reasonable
expectation of success. “Citing KSR, the Board stated that
“when there is a motivation to solve a problem and there are a
finite number of identified, predictable solutions, a person of
ordinary skill has good reason to pursue the known options
within his or her technical grasp”.” See In re Kubin, 561 F.3d
1351 (Fed. Cir. 2009).
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Ans. 4—5; see also id. at 6 (“[MJaking a library of vectors containing a
siRNA targeting a HLA protein is a simple substitution.”).
As discussed above, however, Rossi discloses that its single vector
may be configured to target multiple HLA mismatches. Rossi 172. The
Examiner does not explain with any degree of specificity why either Uchida
or Radcliffe suggests that preparing a library containing multiple vectors,
from which one must pick and choose suitable elements (as the Examiner
argues), would be considered substantially equivalent to simply preparing a
vector that contains multiple sequences capable of inhibiting distinct HLA
genes, as taught by Rossi.
Indeed, the Examiner does not discuss the teachings in either
Radcliffe or Uchida with any degree of specificity. The Examiner,
therefore, has not provided adequate evidentiary support for the contention
that arriving at the process in Appellants’ claim 1 from the teachings in
Rossi amounts to a simple substitution of one known prior art element for
another. While we acknowledge Radcliffe’s disclosure of preparing a
library of vectors that include modulator genes, selectable markers, and
regulatory sequences (see Radcliffe p. 81 (claims 48 and 59)), we find the
Examiner’s indicated motivation to substitute Radcliffe’s vector library,
from which one must pick and choose suitable elements, for Rossi’s single
vector that already contains those elements insufficient to establish a prima
facie case of obviousness.
In sum, for the reasons discussed, we agree with Appellants that the
Examiner has not provided a persuasive, specific, fact-based explanation as
to why Rossi, Uchida, and Radcliffe would have suggested the process
recited in Appellants’ claim 1 to an ordinary artisan. Accordingly, we
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reverse the Examiner’s rejection of that claim, and its dependent claims,
over those references.
REVERSED
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