Ex Parte LESCH et al

Patent Trial and Appeal Board

Dec 14, 2018

14862731 (P.T.A.B. Dec. 14, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/862,731 09/23/2015 Hanna P. LESCH
22925 7590 12/18/2018
PHARMACEUTICAL PATENT ATTORNEYS, LLC
55 MADISON A VENUE
4THFLOOR
MORRISTOWN, NJ 07960-7397
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.
GB07/02695.8 9200
EXAMINER
NGUYEN, QUANG
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
12/18/2018 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@LicensingLaw.net
administration@LicensingLaw.net
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HANNA P. LESCH, KARI J. AIRENNE, and
SEPPO YLA-HER TTUALA 1
Appeal2017-010767
Application 14/862, 731
Technology Center 1600
Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a viral
vector, which have been rejected for lack of adequate written description,
indefiniteness, and anticipation. We have jurisdiction under 35 U.S.C.
§ 6(b ).
We affirm.
1 Appellants identify the Real Party in Interest as Trizell Limited. Appeal Br.
1.
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STATEMENT OF THE CASE
"Lentiviruses, such as Human Immunodeficiency Virus I, are
promising tools for gene therapy due to their ability to transduce and
integrate into the genome of both dividing and non-dividing cells." Spec.
1: 5-7. The Specification discloses that "hybrid baculoviruses may be very
useful to solve the problems regarding large scale production of lentivirus
vectors." Id. at 7:3--4.
"Baculoviruses have several advantages for vector production. They
have a large insert capasity [sic], and are capable of transducing many
mammalian cell lines with high efficiency. However, baculoviruses are not
able to replicate in mammalian cells and viruses are easy to produce in high
titers." Id. at 5:13-16.
Claims 12-14 and 18-20 are on appeal. Claim 12 is illustrative and
reads as follows:
12. A viral vector able to transduce a human cell, said viral
vector produced by a mammalian producer cell transduced with
a recombinant insect virus.
App. Br. 35 (Claims Appendix).
The claims stand rejected as follows:
Claims 12-14, 18, and 20 under 35 U.S.C. § 112(a) for lack of
adequate written description (Final Action2 3);
Claim 14 under 35 U.S.C. § 112(b) as indefinite (Final Action 5);
2 Office Action mailed Dec. 5, 2016.
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Claims 12-14 and 18-20 under 35 U.S.C. § I02(a)(1) 3 as anticipated
by Leblois-Prehaud4 (Final Action 5);
Claims 12-14 and 18-20 under 35 U.S.C. § I02(a)(l) as anticipated
by Kingsman5 (Final Action 9); and
Claims 12-14 and 18-20 under 35 U.S.C. § I02(a)(l) as anticipated
by Schauber6 (Final Action 12).
I
The Examiner has rejected claims 12-14, 18, and 20 for lack of
adequate written description, on the basis that "the instant claims encompass
a viral vector able to transduce a human cell, wherein the viral vector is
produced by a mammalian producer cell transduced with any recombinant
insect virus and not necessarily limited to a recombinant baculovirus." Final
Action 3--4 ( emphasis omitted). The Examiner finds that "the instant
application does not teach or remotely suggests the use of any recombinant
insect virus other than recombinant baculovirus to transduce a mammalian
producer cell to generate a viral vector able to transduce a human cell." Id. at
4.
Appellants argue that "to attack the inventors' written description the
Examiner must provide us with evidence showing, for example, that for this
3 The Examiner actually relied on "pre-AIA 35 U.S.C. I02(b)" (Final Action
5), but the filing date ( actual and effective) of the instant application is Sept.
23, 2015, so the provisions of the Leahy-Smith America Invents Act apply.
4 US 6,387,670 Bl, issued May 14, 2002.
5 WO 98/55640, published December 10, 1998.
6 US 6,863,884 B2, issued March 8, 2005.
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use the artisan distinguished between different kinds of insect viruses. The
Examiner, however, provides no such evidence." Appeal Br. 5.
We will affirm this rejection. "In the context of the written description
requirement, an adequate prima facie case must ... sufficiently explain to
the applicant what, in the examiner's view, is missing from the written
description." Hyatt v. Dudas, 492 F.3d 1365, 1370 (Fed. Cir. 2007).
Id.
Adequate written description means that, in the specification,
the applicant must 'convey with reasonable clarity to those
skilled in the art that, as of the filing date sought, he or she was
in possession of the [ claimed] invention.' Vas-Cath, Inc. v.
Mahurkar, 935 F.2d 1555, 1563---64 (Fed. Cir. 1991). When no
such description can be found in the specification, the only
thing the PTO can reasonably be expected to do is to point out
its nonexistence.
Here, the Examiner expressly stated that what was missing from the
Specification was a description of recombinant insect viruses other than
baculovirus. Thus, the Examiner properly set forth a prima facie case,
because Appellants were "clearly notified of what exactly the Examiner felt
was missing by way of written description." Id. at 1371. "The burden was
then properly shifted to [Appellants] to cite to the examiner where adequate
written description could be found, or to make an amendment to address the
deficiency." Id. Appellants have pointed to nothing in the Specification
describing the limitation pointed to by the Examiner.
Appellants also argue that "a Specification need not describe the
subject matter of a claim literally .... Rather, all that is required is that the
artisan 'could derive' the claimed matter from the disclosure." Appeal Br. 6.
Appellants argue that "the inventors were the first to use insect viruses to
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transduce mammalian producer cells. Given this disclosure, the artisan could
easily derive the claimed range." Id.
Again, we disagree with Appellants' reading of the case law. "[T]he
test requires an objective inquiry into the four comers of the specification
from the perspective of a person of ordinary skill in the art. Based on that
inquiry, the specification must describe an invention understandable to that
skilled artisan and show that the inventor actually invented the invention
claimed." Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed.
Cir. 2010) (en bane).
The Ariad court expressly stated that "while the description
requirement does not demand any particular form of disclosure, or that the
specification recite the claimed invention in haec verba, a description that
merely renders the invention obvious does not satisfy the requirement." Id.
at 1352. Thus, the proper test for written description requires more than a
description that allows those skilled in the art to "derive" a claimed genus.
Rather, "the test for sufficiency is whether the disclosure of the application
relied upon reasonably conveys to those skilled in the art that the inventor
had possession of the claimed subject matter as of the filing date." Id. at
13 51. That test has not been met here. We note that "to satisfy the written
description requirement for a claimed genus, a specification must describe
the claimed invention in such a way that a person of skill in the art would
understand that the genus that is being claimed has been invented, not just a
species of the genus." Carnegie Mellon Univ. v. Hoffmann-La Roche Inc.,
541 F.3d 1115, 1124 (Fed. Cir. 2008). Just as there was no evidence that the
single polymerase gene sequence in Carnegie was representative of all
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polymerase genes, so too here, there is no evidence that the single insect
virus disclosed is representative of all insect viruses. See id. at 1125.
We therefore affirm the rejection of claim 12 under 35 U.S.C.
§ 112(a) for lack of adequate written description. Claims 13, 14, 18, and 20
have not been argued separately and therefore fall with claim 12. 37 C.F.R.
§ 4I.37(c)(l)(iv).
II
The Examiner has rejected claim 14 under 35 U.S.C. § 112(b) as
indefinite. The Examiner concludes that "the metes and bounds of the term
'derived from' are unclear. It is unclear the nature and number of steps
required to obtain a derivative of 'virus'. The term implies a number of
different steps that may or may not result in a change in the functional
characteristics of a virus from the source that a virus is 'derived from'."
Final Action 5.
Appellants argue that "a vague claim term is proper when the term is
about as precise as the subject matter permits .... To prove a violation of
Section 112, second paragraph, the Office must point to evidence of record
showing that artisan would not be able to understand what is claimed."
Appeal Br. 4. Appellants argue that "the Examiner has not provided any
such evidence." Id. 7
We will affirm this rejection. As the Examiner points out, the phrase
"derived from" implies that the original virus is changed in some way, but it
7 Appellants also argue that "the Examiner does not dispute that the artisan
can easily understand what is claimed." This position, however, is not
consistent with the Examiner's statement of the rejection.
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is unclear what types of changes and how many changes are required or
allowed by the claim language. We therefore agree with the Examiner that
the scope of claim 14 is unclear. Appellants have pointed to no definition of
"derived from" in the Specification, and have not shown that the term has
any specific art-recognized meaning. We therefore affirm the rejection of
claim 14 under 35 U.S.C. § 112(b).
III
The Examiner has rejected claims 12-14 and 18-20 as anticipated by
Leblois-Prehaud. The Examiner finds that Leblois-Prehaud teaches "a
method for producing any recombinant virus ( e.g., adenovirus, adeno-
associated virus and retrovirus) based on the use of one or more
baculoviruses for providing the complementary functions ... for the
defective recombinant genome in competent host cells such as 293 cells."
Final Action 6. "Leblois-Prehaud et al also stated 'The viruses thus produced
can be used for the cloning, transfer and expression of genes in vitro, ex vivo
or in vivo . ... "' Id. at 6-7.
We agree with the Examiner that Leblois-Prehaud anticipates claim
12. Leblois-Prehaud states that "[v]ectors of viral origin are widely used for
the cloning, transfer and expression of genes in vitro ... , ex vivo or in
vivo." Leblois-Prehaud at 1:12-16. "One of the lines known for the
production of defective adenoviruses is for example the line 293 into which
part of the adenovirus genome has been integrated. More precisely, the line
293 is a human embryonic kidney cell." Id. at 34--37. "The use of lines can
however have certain disadvantages," including difficulty "to avoid the
production of replicative contaminant viruses (RCA)." Id. at 4:5-11.
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"The second approach consists in cotransfecting with the defective
viral genome a construct (plasmid or adenovirus) providing the
complementation functions." Id. at 4:33-35. "The disadvantage of using a
helper adenovirus lies mainly in the increased risks of recombination
between the adenoviral vector and the helper adenovirus, and in the
difficulty of separating the recombinant from the helper." Id. at 4:43--46.
Leblois-Prehaud discloses "a new system for the production of viruses
which makes it possible to overcome these disadvantages. The system of the
invention is based on the use of a baculovirus to provide the
complementation functions." Id. at 4:52-56. Leblois-Prehaud states that
"baculovirus constitutes an inert vector which can be advantageously used
for the transfer and expression of virus complementation functions into
mammalian, particularly human, cells." Id. at 5:63---66. Leblois-Prehaud
states that the recombinant viruses produced by its method "can be used for
the cloning, transfer and expression of genes in vitro, ex vivo or in vivo." Id.
at 16:59---60. "These viruses may be used in vitro for the production of[]
recombinant proteins .... They may also be used in vivo, for the creation of
animal models or of transgenic animals. They may also be used for the
transfer and expression of genes in vivo, in animals or man, in gene or cell
therapy procedures." Id. at 17:24--31.
Thus, Leblois-Prehaud discloses the production of recombinant
viruses (i.e., vectors) able to transduce a human cell, the vectors produced by
a mammalian producer cell transduced with a recombinant baculovirus (i.e.,
an insect virus). Leblois-Prehaud therefore anticipates claim 12.
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Appellants argue that Leblois-Prehaud fails to enable the claimed
invention: "The instant inventors transfect human cells with insect virus. In
contrast, Leblois proposes achieving the same end not with transfection, but
infection .... Leblois here proposes the impossible. Baculovirus cannot not
[sic] infect human cells." Appeal Br. 8. Appellants cite several references as
evidence that "[i]nfection requires the virus replicate in the host cell,
forming progeny which then spread to neighboring cells." Appeal Br. 8,
n.1. 8
Along a similar line, Appellants argue that
Leblois advises measuring infection by measuring the blue
color produced by lacZ transgene expression. See Leblois at
18:61 to 19:3. Wrong again. Blue color shows transgene
expression, not viral replication. The artisan could measure
transgene expression an infinite number of times, and still not
be able to say whether or not virus is replicating. Blue color
does not measure infection.
Id. at 9.
Both of these arguments are unpersuasive because they depend on
Appellants' definition of infection as requiring viral replication. Leblois-
Prehaud, however, relies on a different definition of "infection," because it
expressly states that one of "the advantages of the system of the invention"
is that "since the baculovirus does not replicate in human cells, the viral
8 It is unclear whether the cited references were considered by the Examiner,
because the Examiner both initialed each of the citations and lined through
them as well. See the "List of References cited by applicant and considered
by examiner" mailed June 23, 2017. The Examiner did, however, address at
least two of the cited reference in the Answer (page 8), so we will assume
that the references are part of the record.
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preparation obtained is not contaminated by the baculovirus." Leblois-
Prehaud 5:23-30 (emphasis added). Thus, when Leblois-Prehaud states that
"the applicant has shown that it was possible, with a recombinant
baculovirus, to infect cells of human origin such as immortalized embryonic
cells" (id. at 5:55-57), it is not using "infect" to indicate viral replication.
Nor do Appellants identify a limiting definition of the term "infection" in
their Specification that distinguishes their use of the term from the infections
in Leblois-Prehaud. Appellants' argument that is not enabling because it
does not use the same definition of "infection" is therefore unpersuasive.
Appellants also argue that "[a]s producer cells, Leblois proposes using
mammalian fibroblast cells and human A549 lung carcinoma cells" but
"[i]nsect virus cannot ... transduce (evoke transgene expression) such
cells." Appeal Br. 10. Appellants also argue that "[s]imilarly, Leblois
proposes using HepG2 cells. Applicant's own unpublished development
work, however, shows baculovirus is not able to transduce HepG2 cells for
the purpose in the Leblois patent (i.e., simultaneous transduction with very
high MOI and/or several viruses)." Id. (citing two declarations under 37
C.F.R. § 1.132 signed in March 2017).
These arguments are unpersuasive because Leblois-Prehaud suggests
that its method can be practiced with any of a variety of cells:
Advantageously, the cells used are hepatic, muscular,
fibroblastic, embryonic, nerve, epithelial (pulmonary) or ocular
(retinal) cells. There may be mentioned, by way of nonlimiting
example, the cells 293 or any derived cell comprising an
additional complementation function (293E4, 293E2a, and the
like), the A549 cells, the HuH7 cells, the Hep3B cells, the
HepG2 cells, the human retinoblastic cells (HER, 911 ), the
He La cells, the 3 T3 cells or the KB cells.
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Leblois-Prehaud 16: 13-21. Thus, even assuming that Leblois-Prehaud' s
method would not work with fibroblast cells, A549 cells, or HepG2 cells,
Appellants' argument does not show that the reference is not enabling for
the other types of cells that it discloses.
Appellants next argue that "[ w ]hen Leblois filed her patent, it was
conventional in the art to use Vesicular Stomatitis Virus glycoprotein (VSV-
G) to pseudotype virus produced in mammalian cells. Leblois thus naively
proposes doing the same in insect producer cells. See 9:45-54." Appeal Br.
11. Appellants argue, however, that
Id.
[w]hile VSV-G is acceptable in mammalian cells, in insect cells
it is fusogenic and toxic. This quality apparently derives not
from the inherent properties of VSV-G, but from in vitro cell
culture conditions: unlike mammalian cells, insect cells are
cultured at an acidic pH (-6.0), and acid pH renders VSV-G
fusogenic. Thus, if used in insect cell cultures, VSV-G fuses the
plasma membranes of adjacent cells, forming syncytia.
This argument is also unpersuasive. The cited passage reads as
follows:
Furthermore, the baculovirus used may be modified to
enhance/change its tropism. It is indeed possible to modulate
the tropism of the viral vectors by modifying their surface
proteins so as (i) to limit it by fusion of the viral proteins with a
specific ligand (light immunoglobulin chain, Gastrin-Releasing
Peptide) or (ii) to broaden it by formation of pseudotypes with a
heterologous viral glycoprotein [G of the Vesicular Stomatitis
Virus (VSV)].
Leblois-Prehaud 9:45-52. Again, even assuming that VSV-G is toxic to
insect cells, Appellants' argument does not show that the reference is
nonenabling because Leblois-Prehaud describes modifying the tropism of
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the baculovirus only as one optional embodiment, and describes two ways of
doing so, of which pseudotyping with VSV-G is only one possibility.
Appellants also argue that
[a] deno-associated virus replication requires expression of the
rep gene. Leblois correctly recognizes this. See Figure 5 and
17 :45-4 7. Leblois, however, proposes using only one rep gene.
See Figure 5. Proper complementation, however, requires
proper post-translation splicing of the rep polypeptide to
produce several different Rep proteins.
Appeal Br. 12. Appellants also argue that "having several polypeptides is
necessary, but not sufficient. Rather, each of the species must be present in
the correct relative proportion." Id. at 13. Similarly, Appellants argue that
the schematic diagram shown in Leblois-Prehaud' s Figure 5 would be
unworkable because it relies on homologous recombination and that method
would not work or would take an unreasonable amount of experimentation.
Id. at 14--15. Appellants also argue that the adeno-associated virus (AA V)
embodiment of Leblois-Prehaud shown in its Figure 5 would provoke
"super-infection restriction." Id. at 18-19.
These arguments are also unpersuasive, for much the same reason as
the arguments addressed above: they focus on the AA V embodiment of
Leblois-Prehaud's disclosure and, even assuming the arguments are
accurate, they do not show that the other disclosed embodiments are not
enabled. See Leblois-Prehaud at Figures 1--4 (showing adenovirus
embodiments), columns 14--15 (describing an adenovirus embodiment); cf
id. at column 15, lines 62---64 ("The genome of AA V or the defective
retrovirus may also be introduced in the form of a virus, a genome or a
plasmid, according to the techniques described above."). See also id. at
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claim 1 ("[a] process for producing a defective recombinant adenovirus")
and claim 23 ("[a] process for producing a defective recombinant adeno-
associated virus"). Again, even if the adeno-associated virus is not enabled,
Appellants' argument does not show that the reference is nonenabling for
other embodiments.
Finally, with respect to Leblois-Prehaud's enablement, Appellants
argue that "Leblois proposes a four part process: establishing a mammalian
cell culture, exposing those cells to baculovirus, culturing the resulting cells
and harvesting the resulting vector." Appeal Br. 16. Appellants argue that
the first three steps were conventional in the art, but the fourth step--
harvesting the vector-would not have worked, because "[t]he artisan
following Leblois, however, would find no expressed product in the
medium. Nor would the artisan find any viable cells on the culture
flask/plate. Following Leblois, the artisan would produce a dead culture." Id.
at 17. As supporting evidence, Appellants cite the 2017 Lesch Declaration9
and the Airenne Declaration. 10 Id.
Both Declarations state that the inventors tried the four-part process
described by Leblois-Prehaud (Lesch Declaration ,r,r 9-12 11 ) but "[i]n
attempting to harvest vector ... , we surprisingly found that the culture did
not contain vector as it appeared that exposure to needed multiple
9 Declaration under 37 C.F.R. § 1.132 of Hanna Lesch, signed March 28,
2017.
10 Declaration under 37 C.F.R. § 1.132 of Kari Airenne, signed March 28,
2017.
11 The Declarations are substantively identical, so we cite only to the Lesch
Declaration.
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baculoviruses with high MOI was cytotoxic to the cells, i.e., the cells were
dying." Id. ,r 13. Both Declarations also state that, as evidence of the
difficulty of producing the claimed viral vector, "I attach true and correct
photocopies of four pages taken from various laboratory notebooks
documenting this research." Id. ,r 7.
Neither Declaration, however, includes any photocopies from
laboratory notebooks. 12 Thus, Appellants' argument is unsupported by
objective evidence of record. "[A] presumption arises that both the claimed
and unclaimed disclosures in a prior art patent are enabled." Amgen, Inc. v.
Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1355 (Fed. Cir. 2003). "The
applicant, however, can then overcome th[e] rejection by proving that the
relevant disclosures of the prior art patent are not enabled." Id. Here,
Appellants' argument, unsupported by objective evidence in the record, is
inadequate to overcome the presumption that Leblois-Prehaud does not
enable what it discloses.
Appellants argue that Leblois-Prehaud does not disclose all of the
limitations of the claims. Specifically, Appellants argue that Leblois-
Prehaud teaches a vaccine, not a vector as recited in the claims. Appeal Br.
20-21. Leblois-Prehaud, however, expressly states that its "invention relates
to a method for the production of recombinant viruses. It also relates to
constructs used for carrying out this method, the producing cells, and the
12 New copies of the Declarations including the cited evidence were filed
October 3, 2017, after the appeal had been docketed at the Board on Aug.
24, 2017, and well after the Examiner could review the evidence and decide
its probative value with respect to the rejections. The evidence attached to
the later-filed Declarations was therefore not timely filed.
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viruses thus produced. These viruses can be used as vector for the cloning
and/or expression of genes." Leblois-Prehaud 1 :6-10.
Similarly, Appellants argue that "Leblois also shows that her
adenovirus lacks a trans gene .... It thus is a vaccine, but not a vector."
Appeal Br. 21. Appellants argue that
Leblois does not anticipate Claims 12 and 21 because Leblois'
own Figures show her VLPs do not have therapeutic
transgenes. They are vaccines, not vectors. They cannot
transduce cells as claim 12 requires.
Similarly, Claims 13 and 22 require a therapeutic transgene.
Leblois cannot anticipate Claims 13 and 22 because Leblois'
VLPs do not have therapeutic transgenes. See Figures 1-5;
17:35-48.
Id. at 22.
This argument is also unpersuasive. First, as discussed above, Leblois-
Prehaud expressly describes its recombinant viruses as vectors. Second,
claim 12 does not require a therapeutic transgene. 13 Third, while claim 13
does require a therapeutic transgene, Leblois-Prehaud describes the use of its
viruses to express numerous therapeutic proteins. Leblois-Prehaud 16:59 to
17:23. Leblois-Prehaud therefore discloses the additional limitation of claim
13.
Finally, with respect to this rejection, Appellants argue that
"[a]denovirus is quite common, causing, e.g., the common cold" and thus
"many ( or most) humans have pre-existing antibodies against adenovirus."
Appeal Br. 22. Appellants argue that "pre-existing immunity against a gene
13 Claims 21 and 22 were withdrawn from consideration by the Examiner
(Final Action 1) and are not on appeal.
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therapy vector was considered fatal because pre-existing anti-viral
antibodies would destroy the vector before it transduces the patient's cells.
Leblois does not suggest that her adenovirus avoids this." Id. at 23.
This argument is unpersuasive for two reasons. First, Appellants cite
no evidence to support the argument, and "[a]ttomey's argument in a brief
cannot take the place of evidence." In re Pearson, 494 F.2d 1399, 1405
(CCPA 1974). Second, Appellants point to no claim language that requires
the claimed vector to be used for gene therapy, and Leblois-Prehaud states
that its viruses can be used for a variety of purposes, including gene therapy
but also including in vitro use to produce recombinant proteins. Leblois-
Prehaud 17 :24--31.
In summary, we affirm the rejection of claims 12 and 13 as
anticipated by Leblois-Prehaud. Claims 14 and 18-20 have not been argued
separately and therefore fall with claim 12. 37 C.F.R. § 4I.37(c)(l)(iv).
IV
The Examiner has rejected claims 12-14 and 18-20 as anticipated by
Kingsman. The Examiner finds that "Kingsman discloses at least the
production of recombinant retroviral particles, including HIV particles, in a
baculovirus expression system." Final Action 9. The Examiner finds that
"Kingsman also teaches that the recombinant retroviral vector comprises one
or more nucleotide of interest (NOI), including a therapeutic gene capable of
eliciting a therapeutic effect." Id. The Examiner reasons that "[s]ince at least
the recombinant HIV containing a therapeutic gene and generated by the
method of Kingsman, that is able to transfect both dividing and non-dividing
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human cells, it is identical at least structurally, functionally and
encompassed by a viral vector as claimed." Id. at 10.
We agree with the Examiner that Kingsman supports a prima facie
case of anticipation. Kingsman discloses "composition that is capable of
expressing a retroviral particle that is capable of delivering a nucleotide
sequence of interest (hereinafter abbreviated to 'NOI') ... to a site of
interest." Kingsman 1:8-10. The "composition [is] useful in gene therapy."
Id. at 1: 12. "The retroviral particles produced by or from the composition ...
(which may otherwise be expressed as being 'retroviral particle vectors') are
useful for the delivery of one or more NOis to cells in vivo and in vitro, in
particular the delivery of therapeutically useful NOI(s)." Id. at 24:26-29.
"ln a highly preferred embodiment, the novel system uses a
baculovirus expression vector encoding a retroviral vector genome. ln
another preferred embodiment, the present invention provides a baculovirus
expression vector encoding a retroviral vector genome, and to retroviral
vector particles produced by the novel system of the invention." Id. at
1: 56: 18-21. "The retroviral particles ... are typically generated in a suitable
producer cell .... Suitable producer cells include insect cells and
mammalian cells." Id. at 28: 14--29.
Kingsman states that its invention "also provides a pharmaceutical
composition for treating an individual by gene therapy .... The
pharmaceutical composition may be for human or animal usage." Id. at
28:32 to 29:3.
Thus, Kingsman describes retroviral vectors useful for human gene
therapy-and therefore able to transduce a human cell-produced by a
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recombinant baculoviral vector in mammalian cells. Kingsman therefore
discloses all of the limitations of claim 12.
Appellants argue that " [ c] laim 12 requires a mammalian producer cell.
In contrast, Kingsman uses insect cells. We cannot assume that Kingsman
inherently produces a product identical to the claimed one." Appeal Br. 23.
This argument is unpersuasive because Appellants have provided no
evidence, or convincing technical reasoning, to conclude that a viral vector
produced in an insect cell differs structurally from the same vector produced
in a mammalian cell. In any case, Kingsman discloses that suitable producer
cells include both insect cells and mammalian cells.
Appellants also argue that "Kingsman teaches that insect cells, when
used as producer cells, do not produce functional gene therapy viral
particles. Rather, Kingsman says that insect cells produce 'virus-like'
particles, i.e., particles which are antigenic like a virus, but which cannot
transduce or infect a cell as a true virus would." Appeal Br. 24. In support of
this position, Appellants quote statements from Kingsman, page 22, line 26,
to page 23, line 11.
This argument is also unpersuasive, because Kingsman's discussion
on pages 22 to 23 addresses what was known in the art before Kingsman' s
disclosure. See Kingsman 22:26-27 ("It is known that insect baculovirus
expression systems have been used for the production of retroviral virus-like
particles (VLPs)") and id. at 23:6 ("However, it is to be noted that VLPs are
proteinaceous particles without a viral genome."). See also id. at 24:26-28
(""The retroviral particles produced by or from the composition of the
present invention ( which may otherwise be expressed as being 'retroviral
particle vectors') are useful for the delivery of one or more NO Is to cells in
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vivo and in vitro."). Thus, Kingsman discloses a solution to the problems in
the prior art described in the passage cited by Appellants.
Claims 13, 14, and 18-20 have not been argued separately and
therefore fall with claim 12. 37 C.F.R. § 4I.37(c)(l)(iv).
V
The Examiner has rejected claims 12-14 and 18-20 as anticipated by
Schauber. The Examiner finds that Schauber discloses
a lentiviral packaging system; including a third-generation
lentiviral packaging system, comprising at least: (i) a first
vector comprising a gag, a pol, or gag and pol genes; (ii) a
second vector comprising a functionally modified or
heterologous envelope gene (including and not necessarily
limited to baculovirus envelope protein bp64 and VSV-G); and
(iii) a third vector comprising a rev gene; and a producer cell
comprising the packaging system and a lentiviral transfer
vector comprising a transgene.
Final Action 12.
We agree with the Examiner that Schauber supports a prima facie case
of anticipation. Schauber discloses "retroviral vectors and their use in gene
therapy." Schauber 1:8-9. Schauber states that its invention "offers
advantages over conventional retroviral gene delivery systems through
unexpected pseudotyping of retroviruses with baculoviral envelope
proteins." Id. at 2:65 to 3:2. Schauber states that its invention
provides a retroviral packaging system that comprises at least
two vectors: a first vector comprises a first nucleotide sequence
comprising a gag, a pol, or gag and pol genes; and a second
vector comprises a second nucleotide sequence comprising a
heterologous or functionally modified envelope gene.
Preferably, the heterologous or functionally modified envelope
gene is a baculoviral envelope gene .... In a preferred
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embodiment, the retroviral elements are derived from a
lentivirus, such as HIV.
Id. at 3:6-15.
Schauber's invention also includes "a producer cell that comprises the
packaging system of the invention and a retroviral transfer vector
comprising a transgene." Id. at 3:22-24. "A retroviral transfer vector of the
present invention can be introduced into a packaging cell line, via
transfection, transduction or infection, to generate a producer cell or cell
line." Id. at 10:12-15. "The packaging vectors of the present invention can
be introduced into human cells or cell lines by standard methods." Id. at
10:29-31.
In a working example, Schauber states that "[t]he VSV-G and
baculovirus (AcNPV) gp64 envelope genes were subcloned into a
mammalian expression vector" and "[l]arge-scale production of pseudotyped
vectors employed in the present examples were produced ... as follows: low
passage 293T cells were expanded and seeded at 5.75 x 108 cells per cell
factory." Id. at 28:16-20. 293T cells are human embryonic kidney cells. Id.
at 4:37-38. "[P]seudotyped HIV vector particles were prepared and tested
for their ability to transduce three human cell lines." Id. at 29: 10-13. "The
results ... demonstrate[ d] that gp64-pseudotyped vector was infectious on
all three cell lines." Id. at 29:21-22.
Thus, Schauber discloses producing a viral vector able to transduce
human cells, produced by a mammalian producer cell transduced with an
expression vector encoding a baculovirus envelope protein. While the
producer cells were not transduced with a baculovirus itself, we agree with
the Examiner (Final Action 13) that the evidence is sufficient to shift the
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burden to Appellants to show that the claimed viral vector differs
structurally from the one disclosed by Schauber.
Appellants argue that "[a]s of the critical date, ... insect virus was not
known in the art as suitable to transduce mammalian producer cells.
Schauber's suggestion to use vectors 'known in the art' as suitable does not
encompass the claimed insect virus because insect virus was not known in
the art as suitable." Appeal Br. 30. Claim 12, however, is directed to a
product, not a method. In addition, "a presumption arises that both the
claimed and unclaimed disclosures in a prior art patent are enabled," Amgen,
Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1355 (Fed. Cir. 2003),
and Appellants do not provide evidence that Schauber does not enable what
it discloses.
Appellants also argue that "Schauber teaches to use 293 and similar
'encapsidation' cell lines as producer cells. Leblois, however, notes that such
encapsidation cells 'hardly make it possible to avoid the production of
replicative contaminant viruses."' Appeal Br. 30. Appellants argue that a
replicative contaminant virus can cause disease, and thus "is not suitable as a
gene therapy vector." Id. at 30-31. Similarly, Appellants argue that
Schauber would require undue experimentation because it "does not teach
any way to filter Schauber' s vector to remove infectious AIDS virus" and
"Schauber's cell lines do not enable one to obtain high recombinant virus
titres." Id. at 32-33.
Claim 12, however, does not require a viral vector that is suitable for
human gene therapy or is in a composition lacking any other virus or that is
present in high titer. All that claim 12 requires is a single viral vector that is
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able to transduce a human cell, either in vitro or in vivo. Claim 12 does not
exclude the presence of replicative contaminant viruses in a composition that
includes the claimed virus. Appellants' argument therefore does not
distinguish the claimed viral vector from that disclosed by Schauber. See In
re Thorpe, 777 F.2d 695, 697 (Fed. Cir. 1985) ("even though product-by-
process claims are limited by and defined by the process, determination of
patentability is based on the product itself;" "[t]he patentability of a product
does not depend on its method of production;" and "[i]f the product in a
product-by-process claim is the same as or obvious from a product of the
prior art, the claim is unpatentable even though the prior product was made
by a different process.")
Appellants also argue that "Schauber Produces A Weak Product"
because it "teaches to get plasmid into cells 'by standard methods including
e.g., calcium phosphate transfection, lipofection or electroporation.' In
contrast, the instant inventors introduce foreign nucleic acid into the host
cell by using recombinant baculovirus." Appeal Br. 32 (emphasis omitted).
Claim 12, however, is directed to a viral vector, so any single viral
vector in the prior art anticipates the claims. Appellants' argument is
therefore unpersuasive.
Claims 13, 14, and 18-20 have not been argued separately and
therefore fall with claim 12. 37 C.F.R. § 4I.37(c)(l)(iv).
SUMMARY
We affirm all of the rejections on appeal.
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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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