Ex Parte Elhay et al

Patent Trials and Appeals Board

Jul 3, 2019

14117516 - (D) (P.T.A.B. Jul. 3, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/117,516 11/06/2014
9629 7590 07/08/2019
Morgan, Lewis & Bockius LLP (WA)
1111 Pennsylvania Avenue, N.W.
Washington, DC 20004
FIRST NAMED INVENTOR
Martin Elhay
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.
013306-5006-US 8362
EXAMINER
BLUMEL, BENJAMIN P
ART UNIT PAPER NUMBER
1648
NOTIFICATION DATE DELIVERY MODE
07/08/2019 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):
karen.catalano@morganlewis.com
patents@morganlewis.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MARTIN ELHA Y, CHRISTOPHER C. BRODER,
and JIN-AN HUANG
Appeal 2018-004114
Application 14/117,5161
Technology Center 1600
Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and DAVID
COTTA, Administrative Patent Judges.
COTTA, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of producing a protective immune response against a Hendra and/or Nipah
virus in a horse or pig. The Examiner rejected the claims on appeal as
obvious under 35 U.S.C. § 103(a).
We affirm.
1 According to Appellants, the real parties in interest are The Henry M.
Jackson Foundation for the Advancement of Military Medicine, Inc. ("HJF")
and Zoetis Services, LLC. App. Br. 1.
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Application 14/11 7,516
STATEMENT OF THE CASE
The Specification discloses that "He V [Hendra virus] is ... known to
cause fatalities in human and animals and is genetically and
immunologically closely related to NiV ['Nipah virus']." Spec. ,-J 2.
According to the Specification, there are "presently no vaccines or
therapeutics for prevention of infection or disease caused by Nipah virus or
Hendra virus." Id. "Thus, there is a need for Nipah virus or Hendra virus
vaccines and diagnostics that allow for high throughput production of
vaccines and/or diagnostics." Id.
The Specification addresses this need, disclosing "an immunogenic
composition comprising Hendra and/or Nipah virus G protein, an
immunostimulatory complex (ISC) and one or more excipients in an amount
effective to elicit production of neutralizing antibodies against the Hendra
and/or Nipah virus following administration to a subject." Id. ,-i 6. "In some
embodiments, the immunogenic composition comprises a saponin, a
phospholipid, and a steroid." Id.
Claims 16-24, 27, and 28 are on appeal. Claim 16 is illustrative and
reads as follows:
16. A method of producing a protective immune response
against a Hendra and/or Nipah virus in a horse or pig
comprising administering to the horse or pig at least one
injection of an immunogenic composition comprising Hendra
and/or Nipah virus G glycoprotein, wherein the at least one
injection contains about 5 µg to about 100 µg of Hendra virus G
glycoprotein or Nipah virus G glycoprotein, and an
immunostimulatory complex (ISC) comprising a saponin and a
sterol, to produce the protective immune response against the
Hendra and/or Nipah virus following administration to the
horse or pig.
Claim App'x A-2.
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The Examiner rejected claims 16-24, 27, and 28 under 35 U.S.C.
§ 103(a) as being obvious over the combination of Broder as evidenced by
Sjolander3 and McEachem.4
FINDINGS OF FACT
1. Broder discloses that in 1994, two Hendra virus outbreaks
lead to the death of fifteen horses and two people. Broder ,-J 13.
2. Broder discloses:
Experimental infections of the horse and pig have been carried
out with He V and NiV respectively and one naturally NiV-
infected horse has been examined. The pathology caused by
either virus in horses appears to be more severe than that caused
by NiV in pigs. In addition to pigs, He V infection of cats has
also been performed and in this case disease resembles that seen
in horses, characterized by generalized vascular disease with
the most severe effects seen in the lung (28).
Id. ,-J 18.
3. Broder discloses:
In another aspect of the invention, a soluble He V or NiV G
glycoprotein or combinations thereof are used as a subunit
vaccine. The soluble He V or NiV G glycoprotein or
combination thereof may be administered by itself or in
combination with an adjuvant. Examples of adjuvants include,
but are not limited, aluminum salts, water-in-soil emulsions,
oil-in-water emulsions, saponin, QuilA and derivatives, iscoms,
liposomes, cytokines including gamma interferon or interleukin
12, DNA, microencapsulation in a solid or semi-solid particle,
2 Broder et al., US Patent Publication No. 2009/0041772 Al, published Feb.
12, 2009 ("Broder").
3 A. Sjolander et al, Immune Response to ISCOMID Formulations in Animal
and Primate Models, 19 Vaccine 2661-2665 (2001) ("Sjolander").
4 J. McEachem et al., A Recombinant Subunit Vaccine Formulation Protects
Against Lethal Nipah Virus Challenge in Cats, 26 Vaccine 3842-3852
(2008) ("McEachem").
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Freunds complete and incomplete adjuvant or active ingredients
thereof including muramyl dipeptide and analogues, DEAE
dextran/mineral oil, Alhydrogel, Auspharm adjuvant, and
Algammulin.
Id. ,i 96 ( emphasis added).
4. Broder discloses:
[T]he neutralizing antibodies of the invention may be
administered as passive immunotherapy to a subject infected
with or suspected of being infected with Hendra or Nipah virus.
A "subject," includes but is not limited to humans, simians,
farm animals, sport animals and pets. Veterinary uses are also
encompassed by the invention.
Id. iJ 88.
5. Broder discloses that "[t]he subunit vaccine comprising soluble
He V or NiV G glycoprotein or combinations thereof can be administered ...
intramuscularly." Id. ,i 97.
6. Broder discloses that "[ d]osage and schedule of administration
can be determined by methods known in the art." Id. ,i 98.
7. Broder discloses that its compositions may be provided in
containers containing "unit doses, bulk packages ( e.g., multidose packages)
or sub-unit doses." Id. ,i 106.
8. Broder discloses that because the administration of soluble He V
G protein was "able to elicit such a potent immune response with high levels
of neutralizing antibodies, it may provide an avenue for vaccine
development strategies." Id. ,i 127.
9. Sjolander discloses that "ISCOMs® are a particulate adjuvant
system composed of antigen, cholesterol, phospholipid and saponins."
Sjolander at 2661.
10. McEachem discloses a study in which "subunit vaccine
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fonnulation cor1tah11ng only recombinant, soluble, attachment glycoprotein
:from HeV (sGHev) and CpG adjuvar1t was evaluated as a potential Ni\/
vaccine in the cat model.'' l'vkEachern Abstract ln the study:
Eight adult cats vvere immunised intramuscularly \vith vaccine
preparations on day O and on day 21. Each cat received the
same 1 ml dose for both prime and boost injections. All vaccine
doses \Vere given via intramuscular injection. Two animals
received 50 ~ig doses (cat 29-50 and cat 30-50), two animals
received 25 µg doses ( cat 31-25 and cat 32-25 ), tvvo animals
received 5 µg doses (cat 33-5 and cat 34-5) and two animals
received adjuvant-alone ( cat 27-0 and cat 28-0).
Id. at 2.3. Upon oronasal challenge with Nipah virus, "aH vaccinated
animals were protected from disease although virus \Vas detected on day 21
post-challenge in one animal." Id at Abstract.
11, Aucouturier5 discloses:
Adjuvants play an important role in the efficacy of vaccines as
the antigens become more and more purified. Indeed
recombinant proteins or synthetic peptides a.re safor than crude
inactivated micro-organism. but less immunogenic. This can be , __ . .• ....
balanced by specific adjuvants. But there is no universal
adjuvants and their action is not yet clear and rely on different
mechanisms. 'fhen, they must be adapted according to several
criteria, like the target species, the antigens, the type of immune
response, the route of inoculation, or the duration of immunity.
Auocuturier Abstract
12. Sanders6 disckises:
5 J. Aucouturier et al., Adjuvants Designed.for Veterinary and Human
Vaccines, 19 Vaccine 2666-2672 (2001) ("Aucouturier"). Aucouturier was
cited by Appellants as evidence that the ordinary artisan "would recognize
that there is no universal adjuvant." App. Br. 13.
6 M. Sanders et al., ISCQAffM-Based Vaccines: The Second Decade, 83
Immunology and Cell Biology, 119-128 (2004) ("Sanders"). Sanders was
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Another important feature of ISCOJVITJVJ_based vaccines is their
ability to induce adaptive immunity in the presence of pre-
existing antibody, as is the case in nevvbon1s via the acquisition
of maten1al antibodies. In non-human primates and horses,
active immunity was induced in the presence of maternal
antibody against measles virus and equine herpes 2 virus, with
ISCOl\FM-based vaccines, but not vv'ith conventiona1 killed
vaccmes.
Sanders at 121.
13. Sanders discloses:
There are currently two registered ISCOl\FM-based vaccines
for veterinary applications, both fr1r use in horses. The first is
an influenza vaccine that has been administered to more than
one million horses, with no reports of adverse events. The
second, referred to as EquityTM (Pfizer Australia, 1'v1elboume,
Australia), is a recently registered novel peptide vaccine to
control oestrous behavior in mares and fillies.
Id. at 122.
ANALYSIS
Broder discloses the use of a "soluble He V or NiV G glycoprotein or
combinations thereof ... as a subunit vaccine," including with an adjuvant
such as ISCOM. FF3. In rejecting claim 16 as obvious, the Examiner found
that Broder disclosed most of the elements of claim 16. The Examiner
acknowledged, however, that Broder did not disclose the administration of
about 5 µg to about 100 µg of G protein to horses. Ans. 5. The Examiner
also acknowledge that Broder did not disclose the requirement of claim 23
that the first dose be followed by a second dose 21-28 days after the first
dose.
cited by the Examiner in response to Appellants' citation of Aucouturier.
Ans. 11; Final Act. (February 13, 2017 Office Action ("Final Act.")) at 7.
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The Examiner found that McEachem disclosed the administration of
50 µg per dose to cats "in a prime boost immunization method involving cats
with the boosting dose following the priming dose after 21 days." Id.
Based on the combined teachings of Broder and McEachem, the
Examiner concluded that it would have been obvious to administer Broder' s
"Hendra or Nipah G protein[] compositions multiple times with 21 to 28
days between the first and second administration and about 5 to about 100
µg of Hendra G protein per dose; and to administer Hendra or Nipah G
protein combined with an immunostimulatory complex (ISC) and excipient
to horses." Id. at 6. The Examiner found motivation to administer to horses
in Broder' s teaching that they are at risk for infection. Id. The Examiner
found that the ordinary artisan would have been motivated to administer G
protein as claimed because Broder teaches that "compositions that comprise
Hendra or Nipah virus G protein, saponin or ISCOMs and an excipient" may
be used to "elicit neutralizing antibodies against Hendra or Nipah viruses"
and McEachem teach two doses of 5, 25 and 50 µg of G protein, 21 days
apart. Id.
We agree with the Examiner that claims 16-24, 27, and 28 would
have been obvious over cited art. We address the Appellants arguments
below.
Claims 16-20, 27 and 28
Appellants argue claims 16-20, 27, and 28 together. We designate
claim 16 as representative.
Appellants argue that "neither Broder nor McEachem teaches or
suggests a composition having G protein and an ISC composed of a saponin
and a sterol" and thus the cited references fail to teach every element of the
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claimed method. App. Br. 11. We are not persuaded because Broder
expressly teaches that Hendra or Nipah G protein may be combined with an
adjuvant, such as ISCOM (FF3) and Sjolander discloses that "ISCOMs® are
a particulate adjuvant system composed of antigen, cholesterol, phospholipid
and saponins." FF9. Thus, use of an ISCOM adjuvant necessarily includes
a saponin and a sterol. FF9.
Appellants argue that "neither Broder nor McEachem administers an
immunostimulatory complex to horses" instead "Broder administers G
protein, without ISC, to a rabbit and McEachem administers G protein,
without ISC, to a cat." App. Br. 12. Accordingly, Appellants contend that
the ordinary artisan would not reasonably have expected to "develop a
Hendra or Nipah virus vaccine for large animals, such as horses and pigs."
Id. We are not persuaded.
As discussed above, Broder expressly suggests administering a
Hendra or Nipah G protein together with an ISCOM. FF3. The fact that the
prior art includes examples in which G protein was administered without an
ISCOM does not detract from this teaching. In re Mills, 470 F.2d 649, 651
(CCP A 1972) ("[A] reference is not limited to the disclosure of specific
working examples."); In re Chapman, 357 F.2d 418,424 (CCPA 1966) ("A
reference can be used for all it realistically teaches, and is not limited to the
disclosures in its specific illustrative examples.").
As to the claim requirement that the composition be administered to
horses or pigs, Appellants do not identify, and we do not find, anything to
suggest that Broder and McEchem's teachings regarding G protein vaccines
are limited to rabbits and cats. To the contrary, Broder states without
limitation to a particular species, that because the administration of soluble
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He V G protein was "able to elicit such a potent immune response with high
levels of neutralizing antibodies, it may provide an avenue for vaccine
development strategies." FF8. To be fair the "potent immune response" in
this statement was generated in rabbits, but Broder does not limit inference
drawn from this response - that it may provide an avenue for vaccine
development - to rabbits.
Moreover, Broder discloses that Hendra and Nipah viruses can infect
horses and that horses have been experimentally infected with Hendra and
Nipah viruses. FF 1, FF2. And Broder teaches that G protein antibodies can
be administered to subjects including "farm animals" and notes that
"[ v Jeterinary uses are also encompassed by the invention." FF4. Horses and
pigs are reasonably understood as farm animals. We find that these
teachings and McEchem's teaching that administration of a similar HeV G
protein composition immunized cats, would have motivated the ordinary
artisan to administer Broder' s vaccine to horses with a reasonable
expectation of success based on the successful administration to rabbits and
cats. See, e.g., FFl, FF2, FF4, FF8, FFlO.
Appellants acknowledge that there "may be a general disclosure
within Broder that an ISC can be used as an adjuvant," but argue that "the
record does not establish why one of ordinary skill would have had a
specific motivation to choose an ISC from among the many well-known
adjuvants listed in Broder." App. Br. 12. Appellants contend that an
ordinary artisan would have had no motivation to "pick and choose specific
but unconnected portions of McEachem and Broder [to] develop an
administration protocol in which an ISC is used as an adjuvant for
administration to horses or pigs of a Hev G protein or NiV G protein." Id.
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Appellants contend that "different adjuvants can affect each animal's
immune system in different ways" and thus there would be no expectation
that McEachem's "aluminum+ CpG" adjuvant would be equivalent to an
ISCOM. Id. As evidence, Appellants cite Aucouturier as teaching "that one
of skill in the art would recognize that there is no universal adjuvant." Id. at
13. More specifically, Appellants argue that McEachem would suggest to
the ordinary artisan that the positive response reported was "due the
presence of the CpG adjuvant and its interaction with the antigen." Id.
(citing as support, McEachem's statement that "[t]he combination of sGHeV
and CpG induced sufficient levels of antigen-specific plasma lg, neutralising
antibodies and antigen-specific mucosal IgA to protect all cats
from lethal NiV challenge."). We are not persuaded.
As discussed above, Broder expressly suggests to use an ISCOM as an
adjuvant in connection with its soluble He V or NiV G protein. FF3. We
acknowledge that there are r10 universa1 adjuvants and an adjuvar1t must be
adapted to, inter alia, the target species, route of inoculation, and antigen,
FFl L Hmvever, given Broder's suggestion to use an ISCOYvi as an adjuvant
in connection with its antigen (FF3), and given that was known to use
ISCOMs in horse vaccines (FF12, FF13), we agree with the Examiner that it
would have been obvious to use Broder' s He V or NiV G protein together
with an ISCOM adjuvant.
Accordingly, we affirm the Examiner's rejection of claim 16.
Because they were not argued separately, claims 17-20, 27, and 28 fall with
claim 16.
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Claim 21
Claim 21 depends from claim 16 and further requires that the
"immunogenic composition is administered intramuscularly." Appellants
argue that the cited art fails to suggest intramuscular injection. App. Br. 14-
15. Appellants contend that "while Broder may contain the word
'intramuscular,' there is no specific direction or guidance in Broder for IM
administration to a horse or pig of a composition comprising a He V G
protein or NiV G protein, at a dose of about 5 µg to about 100 µg, with an
ISC." App. Br. 14. Appellants similarly contend that "while McEachem
administers a composition containing aluminum + CpG to a cat via IM, there
is no direction to administer an !SC-containing composition via IM to any
other animal." Id. at 15. We are not persuaded.
Both Broder and McEachem expressly disclose intramuscular
injection of their compositions. FF5, FFlO. We agree with the Examiner
that these disclosures are sufficient to render the claimed method of
administration obvious. See, Ans. 12-13.
Accordingly, we affirm the Examiner's rejection of claim 21.
Claims 22-24
Claim 22 depends from claim 16 and further requires that the
"immunogenic composition is administered in multiple doses." Claim 23
depends from claim 22 and further requires that the "first dose is followed be
a second dose at least about twenty-one days to about twenty-eight days
after the first dose." Claim 24 also depends from claim 22 and further
requires that "each dose contains about 5 to about 100 µg of soluble Hendra
virus G glycoprotein."
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Appellants argue that "[t]he collection of cited references ... fails to
suggest multiple injections of a composition having a He V G protein or NiV
G protein and an ISC to a horse or pig." App. Br. 15. We are not persuaded
because Broder discloses packing its compositions in multidose packages
and McEachem discloses administration its compositions in two doses. FF7,
FFlO.
Appellants argue that the claimed dosage amount is non-obvious as
applied to a horse or pig. App. Br. 16. We are not persuaded because as
discussed above, the teachings of the cited art can reasonably be extended to
horses and pigs. With respect to the dosage amount, McEachem teaches
dosage amounts of 5, 25, and 50 µg and Broder teaches that dosage '"can be
determined by methods knmvn in the art!' FF6, FFlO. Using l\foEachem as
a starting point it would have been obvious to determine the appropriate
dosage for a horse or pig using ""methods known in the art" as taught by
Broder. FF6. "[D]iscovery of an optimum value of a result effective
variable in a known process is ordinarily within the skill of the art." In re
Boesch, 617 F.2d 272,276 (CCPA 1980).
Accordingly, \Ve affinn the Examiner's rejection of claims 22-24.
SUMMARY
For the reasons set forth herein, and those set forth in the Examiner
Answer and Final Office Action, we affirm the Examiner's rejection of claims
16-24, 27, and 28 under 35 U.S.C § 103(a) as obvious.
No time period for taking any subsequent action in connection with this
appeal may be extended under 37 C.F.R. § l.136(a)(l).
AFFIRMED
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