Ex Parte Gelder et al

Patent Trial and Appeal Board

Sep 18, 2018

13121796 (P.T.A.B. Sep. 18, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/121,796 06/13/2011 Frank B. Gelder
96039 7590 09/20/2018
Meunier Carlin & Curfman LLC
999 Peachtree Street NE
Suite 1300
Atlanta, GA 30309
UNITED ST A TES OF AMERICA
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.
10 l 27-002US 1 1951
EXAMINER
HAMA, JOANNE
ART UNIT PAPER NUMBER
1647
NOTIFICATION DATE DELIVERY MODE
09/20/2018 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):
docketing@mcciplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte FRANK B. GELDER and GILLIAN ALISON WEBSTER
Appeal2016-008460
Application 13/121,796 1
Technology Center 1600
Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of prophylactic or therapeutic treatment of exposure to radiation or radiation
poisoning, which have been rejected as obvious. We have jurisdiction under
35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
"Exposure to radiation can, in some cases, lead to radiation poisoning,
which is a form of damage to biological tissue due to an increased exposure
to a source of ionising radiation." (Spec. 1) "Many of the symptoms of
1 Appellants identify the Real Party in Interest as Innate Therapeutics
Limited. ( Appeal Br. 3.)
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Application 13/121,796
radiation poisoning are due to the interference of ionising radiation with cell
division." (Id.) Radiogardase, pentetate calcium trisodium (Ca-DTP A) and
pentetate zinc trisodium (ZnDTP A) are known drugs for treatment of
radiation contamination, which work to eliminate radioactive substances
from the human body. (Id. at 2.) Neupogen, which stimulates the growth of
white blood cells and can help repair bone marrow damage, is used in people
who have received chemotherapy or radiation therapy. (Id.) The present
invention is directed to an alternative to these other known drugs, the use of
muramyl dipeptide (MDP) cross-linked into a microparticle. (Id.)
Claims 1-3, 5-13, 15, 16, 18, 20, 23, 26, 29, 31, and 43--45 are on
appeal. Claim 1 is representative and reads as follows:
1. A method of prophylactic or therapeutic treatment of
exposure to radiation or radiation poisoning comprising
administrating Muramyl dipeptides cross-linked to each other to
form a microparticle (MDP-microparticle) or a composition
comprising the MDP-microparticle to a subject requiring such
treatment in an amount effective to prophylactically or
therapeutically treat exposure to radiation or radiation
poisoning, wherein the MDP-microparticle is isolated from
bacteria.
(Appeal Br. 17.)
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The following grounds of rejection by the Examiner are before us on
review:
Claims 1-3, 6-13, 15, 16, 18, 20, and 43--45 under 35 U.S.C. § 103 as
unpatentable over Osada2 and Gelder, 3 as evidenced by Yano, 4 Yokouchi, 5
Namba, 6 Parant, 7 and Pinegin. 8
Claims 5 and 29 under 35 U.S.C. § 103 as unpatentable over Osada,
Gelder, and Namba, as evidenced by Yano, Yokouchi, Parant, and Pinegin.
2 Osada et al., Stimulation of Resistance of Innnunocompromised Mice by a
Muramyl Dipeptide Analog, 37(3) Infection and Immunity, 1285-1288,
(1982).
3 Gelder, WO 98/15658, published Apr. 16, 1998.
4 Yano et al., Restorative effect of romurtide for thrombocytopenia
associated with intensive anticancer drug treatment and/or irradiation in
patients with gastrointestinal cancer, 15(6B), Anticancer Res., 2883-87,
(1995) (Abstract only).
5 Y okouchi et al., Study on the most appropriate time for Romurtide
administration (Nopia) in radiotherapy patients, 24(13) Gan To Kagaku
Ryoho, 1967-73 (1997) (Abstract only). The Examiner mistakenly refers to
Y okouchi as Y okuchi.
6 Namba et al., Romurtide, a synthetic muramyl dipeptide derivative,
promotes megakaryocytopoiesis through stimulation of cytokine production
in nonhuman primates with myelosuppression, 15(4) Vaccine, 405-13
(1997).
7 Parant et al., In vivo and in vitro stimulation of nonspecific immunity by the
beta-D-p-aminophenyl glycoside of N-acetylmuramyl-L-alanyl-D-
isoglutamine and an oligomer prepared by cross-linking with
glutaraldehyde, 138(3) J Infect Dis., 378-86 (1978) (Abstract only).
8 Pinegin, US 5,877,147, issued Mar. 2, 1999. The Examiner mistakenly
refers to Pinegin as Pinegan.
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Claim 23 under 35 U.S.C. § 103 as unpatentable over Osada, Gelder,
and Mcintosh,9 as evidenced by Yano, Yokouchi, Namba, Parant, and
Pinegin.
Claim 26 under 35 U.S.C. § 103 as unpatentable over Osada, Gelder,
and Kekkaku, 10 as evidenced by Yano, Yokouchi, Namba, Parant, and
Pinegin.
Claim 31 under 35 U.S.C. § 103 as unpatentable over Osada, Gelder,
and Spitler, 11 as evidenced by Yano, Yokouchi, Namba, Parant, and Pinegin.
Claims 1-3, 5-13, 15, 16, 18, 20, 23, 26, 29, 31, and 43--45 under the
judicially created doctrine of obviousness-type double patenting as being
unpatentable over claims 1-5, 7, 10-12, 18, 19, 21, 22, and 30 of co-pending
U.S. Application Serial No. 12/935,871 in view ofOsada and Gelder.
DISCUSSION
Claim Construction
Claim 1 requires at least administering (a) Muramyl dipeptides cross-
linked to each other to form a microparticle (MDP-microparticle) or (b) a
composition comprising the MDP-microparticle.
According to the Examiner, Appellants "clarified of record that the
'MDP microparticle' ... is the bacterial cell wall component of muramic
acid cross-linked with a di peptide structure, such as L-alanine-D-
isoglutamine dipeptide exemplified on page 14 of the instant specification."
9 McIntosh, US 4,815,446, issued Mar. 28, 1989.
10 Tsubura, Muramyl dipeptide derivative and its clinical application, 64(11)
Kekkaku 731-39 (1989) (Abstract Only). The Examiner refers to the
reference authored by Tsubura as "Kekkaku."
11 Spitler et al., US 5,925,362, issued July 20, 1999.
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Application 13/121,796
(Final Action 5.) The Examiner finds that "[a] plain reading of the claims,
the specification, and the prior art shows that the MDP microparticle, as
claimed, is drawn to a muramic acid moiety crosslinked via any means,
including amino linkage, to another moiety." (Final Action 5.) The
Examiner contends that "examples of such crosslinking include the L 18-
MDP-ala of Osada and the commercially available romurtide of Yano,
Yokouchi, and Namba, as well as the N-acetylmur[a]myl-L-alanyl-D-
isoglutamine of Parant (from 1978)." (Id.) The Examiner further noted that
the claimed "muramyl dipeptide cross-linked into a
microparticle" is drawn to a genus of compounds, as defined by
the specification at page 14, and the recited "MDP
microparticle' of independent claim 1 is also recited using the
open language 'comprising." As such, any MDP crosslinked
moiety comprising MDP crosslinked into another moiety,
including the L-alanyl-D-isoglutamine and/or LI 8 moiety, is
sufficient to meet Applicant's definition of an MDP
microparticle.
(Final Action 4--5; see also Ans. 13-15.)
During prosecution, claim terms are given their broadest reasonable
construction consistent with the specification. See, e.g., In re Bond, 910
F.2d 831, 833 (Fed. Cir. 1990). We disagree with the Examiner's
interpretation of MDP-microparticle as being muramic acid moiety
crosslinked via any means, including amino linkage, to any other moiety.
That interpretation is not consistent with the Specification.
MDP-microparticle as used in Appellants claims requires that
muramyl dipeptides be cross-linked to each other to form a microparticle;
that is so even in the case where the claim requires what is administered to a
subject be a composition "comprising the MDP-microparticle."
"'Comprising' is a term of art used in claim language which means that the
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named elements are essential, but other elements may be added and still
form a construct within the scope of the claim." Genentech, Inc. v. Chiron
Corp., 112 F.3d 495, 501 (Fed. Cir. 1997). In this case, the named elements
of the MDP-microparticles that are required are muramyl dipeptides that are
cross-linked to each other. Other elements may be contained in the
composition comprising the muramyl dipeptides that are cross-linked to each
other, but it is necessary that the composition includes the muramyl
dipeptides that are cross-linked to each other to form the MDP-
microparticle. The Specification further supports this construction.
It is true, as the Examiner notes, that Appellants' Specification states
that "[t]he MDP microparticles contain muramic acid with amino-linked L-
alanine-D-isoglutamine dipeptide as the bioactive component." (Spec. 14.)
However, the indication of what moiety in the MDP-microparticles is the
bioactive component does not redefine the MDP-microparticle as simply
being muramic acid that is amino-linked to L-alanine-D-isoglutamine, as the
Examiner concludes (Final Action 5 (Appellants "clarified of record that the
'MDP microparticle' ... is the bacterial cell wall component of muramic
acid cross-linked with a di peptide structure, such as L-alanine-D-
isoglutamine dipeptide exemplified on page 14 of the instant
specification.").) The Specification clearly indicates, in the very beginning
of the description of the isolation process of the MDP-microparticle from
Propionibacterium acini, that "[a] multiple repeat of muramyl dipeptide
(MDP) isolated from Propionibacterium acini, formed the core structure of
the MDP microparticle carrier complex of this example." (Spec. 13.) The
Specification then details that particular isolation of MDP from
Propionibacterium acini, from toxic components. (Id. at 14.) However, the
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Specification then clearly states that the MDP-microparticle preparation was
analyzed and demonstrated to be "muramyl dipeptide extensively
crosslinked." (Id.) The Specification later notes, when describing covalent
attachment of ligands to an MDP-microparticle, that due to the "multiple
repeats of muramyl dipeptide, attachment of the subject ligand to aldehyde
groups may be produced by the mild oxidation of sugar residues with, for
example, sodium metaperiodate following mild reduction with sodium
borohydride and the like." (Spec. 16.)
We find the Specification makes it abundantly clear that the MDP-
microparticle includes multiple muramyl dipeptides repeated in the core
structure of the microparticle and that those dipeptides are extensively
crosslinked. And the claims make it clear that this dipeptide unit is a repeat
unit and those repeat units are cross-linked to form the MDP-microparticle.
Obviousness
The Examiner's rejection of the claims as being obvious over the
various combinations of prior art rests on the conclusion that compounds
such as LI 8-MDP-Ala and romurtide, which is "a synthetic muramyl
dipeptide (MDP) derivative (N 2-N-acetylmuramoyl)-L-alanyl-D-
isoglutaminyI-N6-stearoyI-L-lysine (also known as MDP-Lys(Ll 8))" (Final
Action 4), are "within the claimed genus of crosslinked MDP microparticle
moieties." (See, e.g., Final Action 5.)
According to the Examiner, Osada teaches using LI8-MDP-Ala,
"which comports with the crosslinked muramyl dipeptide claimed as an
'MDP microparticle' ," in methods to treat exposure to radiation. (Id. at 3-
4.) The Examiner notes that Gelder teaches MDP microparticles isolated
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from Propionibacterium acini that are extensively crosslinked and that they
are not associated with increases in toxicity and/or decreases in adjuvant
effect, in contrast to MDP microparticles isolated from other species of
bacterium. (Id. at 3.) The Examiner also notes that Gelder teaches that the
"muramyl dipeptide which forms the MDP-microparticle 'can be
synthesized or isolated from certain bacteria such as Prop[] ionibacteruim
acini or the like.' (p. 45, lines 16-32)." (Id.) The Examiner then concludes
that it would have been obvious to one of ordinary skill in the art to
substitute the bacterial-derived MDP-microparticle of Gelder for the LI 8-
MDP-Ala in Osada with a reasonable expectation of success. In particular,
the Examiner states:
Because the claimed MDP microparticle is generic in structure,
other than being amended to now be isolated from generic
bacteria, and both the prior art and the instant specification
recites that its construction may be generated from natural or
synthetic moieties, absent evidence to the contrary, the moieties
taught by Osada and Gelder can be used interchang[ e ]ably for
the same purpose.
(Id. at 4.) According to the Examiner "[t]he Gelder reference itself
recognizes the obvious substitutability of the natural and synthetic MDP
microparticle product, as explained above." (Id.)
For the reasons discussed above concerning the construction of the
claim term MDP-microparticles, we disagree with the Examiner's premise
that Osada teaches an MDP-microparticle as claimed. The mere fact that the
muramyl acid ofLI8-MDP-Ala is crosslinked with a dipeptide structure,
i.e., L-alanyl-D-isoglutamine, does not make LI8-MDP-Ala an MDP-
microparticle as claimed. What is necessary is evidence of crosslinking of
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one MDP monomer to another MDP monomer. The Examiner has pointed
to no such evidence.
As Appellants explain, and the Examiner does not refute, L18-MDP-
Ala is a soluble synthetic single unit ofL18-MDP-ala. (Appeal Br. 9.)
Appellants also explain in detail, and the Examiner does not refute, that none
of the other references cited by the Examiner as providing "examples of
species within the claimed genus of crosslinked MDP microparticles," i.e.,
a) Y ano, Y okouchi, and N amba, which disclose romurtide, b) Parant
disclosing L18-MDP-Ala, and c) Pinegin disclosing a number ofMDP
derivatives (Final Action 4--5), disclose MDP analogs that have repeat MDP
analog units that are crosslinked to each other. (Appeal Br. 9-10.)
In addition to the foregoing, we agree with Appellants that there is no
evidence of record to support that one of ordinary skill in the art would have
substituted the very different structure taught by Gelder for the MDP
analogue taught by Osada with a reasonable expectation of success. (Id. at
11.) First, contrary to the Examiner's conclusion, the Gelder reference does
not recognize the obvious substitutability of the MDP-microparticle obtained
from bacteria and the synthetic MDP product disclosed in Osada, which, as
explained above, is not an MDP-microparticle as claimed.
Second, as Appellants explain, Gelder teaches using an MDP-
microparticle "in the context of a conventional adjuvant-immunogen
complex and does not disclose or suggest that the MDP-microparticle alone
may be effective as a prophylactic or therapeutic agent." (Id.) The MDP-
microparticles are noted to be adjuvants to enhance immune responses to
specific immunogens. (Id.) Indeed, as Appellants explain, Examples 6 and
7 of Gelder provide a comparison to demonstrate "the adjuvant effect of the
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two MDP-imnmnogen conjugates ... by immunizing rabbits with the MDP-
immunogen conjugates emulsified in squalene and comparing the antibody
and cytokine responses to those obtained when conventional adjuvants were
employed (Freund's complete adjuvant, Ribi, Titer Max and Alum)." (Id.)
As Appellants further note "Gelder is silent regarding the use or
effectiveness of crosslinked MDP-microparticles alone." (Id.) Gelder is
also silent regarding the use or effectiveness of bacterially-produced MDP-
microparticles for the treatment of exposure to radiation or radiation
poisoning. (Id. at 12.)
In light of the foregoing, we agree with Appellants that there is
insufficient evidence of record to establish that it would have been obvious
to one of ordinary skill in the art to substitute the MDP-microparticles of
Gelder for the MDP analogues disclosed in Osada ( or for any of the MDP
analogues in the other evidentiary references cited by the Examiner, which
disclose MDP analogues but not MDP-microparticles as claimed) with a
reasonable expectation of success of treating exposure to radiation
(prophylactically or therapeutically).
As such, to the extent that the Examiner has rejected
a) claims 1-3, 6-13, 15, 16, 18, 20, and 43--45 under 35 U.S.C. § 103
as unpatentable over Osada and Gelder, as evidenced by Y ano, Y okouchi,
Namba, Parant, and Pinegin;
b) claims 5 and 29 under 35 U.S.C. § 103 as unpatentable over Osada,
Gelder, and Namba, as evidenced by Yano, Yokouchi, Parant, and Pinegin;
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c) claim 23 under 35 U.S.C. § 103 as unpatentable over Osada,
Gelder, and McIntosh 12, as evidenced by Yano, Yokouchi, Namba, Parant,
and Pinegin;
d) claim 26 under 35 U.S.C. § 103 as unpatentable over Osada,
Gelder, and Kekkaku, 13 as evidenced by Yano, Yokouchi, Namba, Parant,
and Pinegin; and
e) claim 31 under 35 U.S.C. § 103 as unpatentable over Osada,
Gelder, and Spitler, 14 as evidenced by Yano, Yokouchi, Namba, Parant, and
Pinegin, we reverse.
Obviousness-Type Double Patenting
The Examiner provisionally rejected claims 1-3, 5-13, 15, 16, 18, 20,
23, 26, 29, 31, and 43--45 under the judicially created doctrine of
obviousness-type double patenting as being unpatentable over claims 1-5, 7,
10-12, 18, 19, 21, 22, and 30 of co-pending U.S. Application Serial No.
12/935,871 in view of Osada and Gelder. The identified application has
since issued as US Patent 9,415,061, and thus the rejection is no longer
provisional.
12 McIntosh is relied upon by the Examiner for teaching MDPs are small
bacterial cell wall components that activate macrophages. (Final Action 13.)
13 Kekkaku is relied upon by the Examiner for teaching "clinical success of
restoration of leukopenia in patients with cancer receiving cancer
chemotherapy by MDP derivative, muroctasin." (Final Action 15.)
14 Spitler is relied upon by the Examiner for teaching that "radiation is the
mainstay of cancer therapy" and the "[u]se of MDPs in an anticancer
vaccine adjuvant." (Final Action 18.)
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According to the Examiner, the '871 application claims a method of
treating neoplastic disease using MDP microparticles. (Final Action 20.)
The Examiner further notes that "treatments of neoplastic disease frequently
encompass radiation therapy." (Final Action 21.) The Examiner further
notes that the '871 application teaches use of the MDP microparticle for
tumor irradiation. (Final Action 20 (relying on paragraphs 19 and 65 of the
PG Publication 20010165250 and Example 12).)
The Examiner relies on Osada for teaching treating radiation with
MDP-microparticles as claimed. (Final Action 20.) The Examiner notes
that Osada "teaches that the MDP analog enhanced resistance to bacterial
and fungal infections in mice whose defense mechanisms had been
depressed by X-ray radiation or by treatment with cyclophosphamide." (Id.)
The Examiner relies on Gelder for teaching MDP-microparticles
isolated from bacteria used to stimulate immunogenicity in patients. (Id.)
The Examiner posits that
[ o ]ne of ordinary skill in the art would be aware that the subject
population in the method of treating subjects exposed to
radiation of the instant claims would overlap with the subject
population in the method of treating neoplastic disease claimed
in the '871 application, particularly in light of the teachings of
Osada and Gelder, including the isolation of the MDP-
microparticle from bacteria.
(Id.) And according to the Examiner, the evidence establishes that
"[a]lthough the conflicting claims are not identical, they are not patentably
distinct from each other because the claims are drawn to the same subject
matter, that being a method of treatment comprising administering a MDP
microparticle to stimulate an immunostimulatory response in response to
radiation therapy, which is encompassed by anti-neoplastic therapy." (Id.)
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We disagree with the Examiner's conclusion. The claims of the '061
patent are directed to administering "muramyl dipeptide (MDP), wherein the
dipeptide moiety of the MDP is amino linked L-alanine-D-isoglutamine and
the MDP is crosslinked with bacterial DNA." In particular, we note that the
'061 patent claims are not directed to MDP units crosslinked to each other,
but to an MDP analogue crosslinked with bacterial DNA. Thus, the '061
patent claims are not directed to the use of the MDP-microparticles claimed
in the present application. Likewise, Osada is not directed to the use of
MDP-microparticles presently claimed. Furthermore, as noted above, and as
argued by Appellants, "Gelder discloses the use of MDP-microparticles in
the context of a conventional adjuvant-immunogen complex and does not
disclose or suggest that the MDP-microparticle alone may be effective as a
prophylactic or therapeutic agent." ( Appeal Br. 11.)
Thus, we disagree with the Examiner that the compound being
administered in the '061 patent is within the genus of the MDP-microparticle
as required the present application claims. We further disagree that there is
evidence in Gelder of the use or effectiveness of MDP-microparticles in the
absence of immunogen for therapeutic purposes. Consequently, we do not
find sufficient evidence to support the Examiner's conclusion that the
present claims that require administration of an MDP-microparticle for the
prophylactic or therapeutic treatment of exposure to radiation or radiation
poisoning is patentably indistinct from the claims of the '061 patent in view
of Osada and Gelder.
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SUMMARY
We reverse the Examiner's rejection of claims 1-3, 6-13, 15, 16, 18,
20, and 43--45 under 35 U.S.C. § 103 as unpatentable over Osada and
Gelder, as evidenced by Yano, Yokouchi, Namba, Parant, and Pinegin.
We reverse the Examiner's rejection of claims 5 and 29 under 35
U.S.C. § 103 as unpatentable over Osada, Gelder, and Namba, as evidenced
by Y ano, Y okouchi, Parant, and Pinegin.
We reverse the Examiner's rejection of claim 23 under 35 U.S.C.
§ 103 as unpatentable over Osada, Gelder, and McIntosh, as evidenced by
Yano, Yokouchi, Namba, Parant, and Pinegin.
We reverse the Examiner's rejection of claim 26 under 35 U.S.C.
§ 103 as unpatentable over Osada, Gelder, and Kekkaku, as evidenced by
Yano, Yokouchi, Namba, Parant, and Pinegin.
We reverse the Examiner's rejection of claim 31 under 35 U.S.C.
§ 103 as unpatentable over Osada, Gelder, and Spitler, as evidenced by
Yano, Yokouchi, Namba, Parant, and Pinegin.
We reverse the Examiner's rejection of claims 1-3, 5-13, 15, 16, 18,
20, 23, 26, 29, 31, and 43--45 under the judicially created doctrine of
obviousness-type double patenting as being unpatentable over claims US
9,415,061 in view of Osada and Gelder.
REVERSED
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