Ex Parte Schroff et al

Patent Trial and Appeal Board

Dec 10, 2018

13266905 (P.T.A.B. Dec. 10, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/266,905 01/09/2012
23373 7590 12/12/2018
SUGHRUE MION, PLLC
2100 PENNSYLVANIA A VENUE, N.W.
SUITE 800
WASHINGTON, DC 20037
FIRST NAMED INVENTOR
Matthias Schroff
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.
12031.80522 1774
EXAMINER
MCDONALD, JENNIFER SUE PITRAK
ART UNIT PAPER NUMBER
1635
NOTIFICATION DATE DELIVERY MODE
12/12/2018 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):
PPROCESSING@SUGHRUE.COM
sughrue@sughrue.com
USPTO@sughrue.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MATTHIAS SCHROFF, BURGHARDT WITTIG,
MANUEL SCHMIDT, and CHRISTIANE KLEUSS
Appeal2017-000757 1
Application 13/266,905
Technology Center 1600
Before RICHARD M. LEBOVITZ, JEFFREY N. FRED MAN, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims is directed to a concatemeric molecule for
modulation of an activity of a human or animal immune system, and
methods of using it. The Examiner rejected the claims under 35 U.S.C.
§ 102 as anticipated and under 35 U.S.C. § 103 as obvious. Appellants
appeal the Examiner's determination under 35 U.S.C. § 134 that the claims
are unpatentable. We have jurisdiction under 35 U.S.C. § 6(b ).
The Examiner's decision is affirmed.
1 The Appeal Brief ("Br.") identifies Mologen AC as the real party in
interest.
Appeal2017-000757
Application 13/266,905
STATEMENT OF THE CASE
The Examiner finally rejected the claims as follow:
1. Claims 1--4, 12, 14, 16-18, 20, 21, and 25-32 under pre-AIA
35 U.S.C. § I02(b) as anticipated by Schroff et al., WO 2007/131495 A2,
published Nov. 22, 2007. Ans. 2. Because Schroff is in the German
language, the Examiner relied upon CA 2651568 Al ("Schroff') which is an
English equivalent of Schroff et al., WO 2007/131495 A2, in setting forth
the grounds of rejection.
2. Claims 1--4, 12, 14, 16-18, 20-23, and 25-32 under pre-AIA
35 U.S.C. § I03(a) as obvious over Schroff. Ans. 3.
Claims 1 and 2, which are representative of the appealed subject
matter, read as follows
1. A concatemeric molecule for a modulation of an activity
of a human or animal immune system, wherein the
concatemeric molecule comprises four deoxyribonucleic acid
sequences as monomer units, which are covalently bound and
comply with the formula [see Appendix A for the complete
formula].
2. The concatemeric molecule according to claim 1,
wherein the deoxyribonucleic acid sequence as monomer unit
compnse:
i) 5'-
GGGTTACCACCTTCATTGGAAAACGTTCTTCGGGGCG
TTCTTAGGTGGTAACCC-3' (SEQ ID No. 1) or
ii) 5'-
CCCTAGGGGTTACCACCTTCATTGGAAAACGTTCTTCG
GGGCGTTCTTTCCCCAATGGTGGA-3' (SEQ ID No. 4) or
iii) 5'-
CCCTTCCACCATTGGGGATCATTGGAAAACGTTCTTCG
GGGCGTTCTTAGGTGGTAACCCCT-3' (SEQ ID No. 5) or
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iv) 5'-
AGGGGTTACCACCTTCATTGGAAAACGTTCTTCGGGG
CGTTCTTAGGTGGTAAC-3' (SEQ ID No. 6),
wherein the deoxyribonucleic acid sequence as monomer units
each have a maximum length of 400 nucleotides.
ANTICIPATION REJECTION
Claim 1 is directed to concatemeric molecule comprising four DNA
monomer units which are covalently bonded together. The monomer has
the general formula recited in claim 1. Claim 2, which depends from claim
1, lists the sequences of four specific DNA molecules, each which
corresponds to the formula of claim 1.
The Examiner found that Schroff describes a DNA molecule
comprising the sequence of the first DNA listed in claim 2 having SEQ ID
NO: 1. Final Act. 3. The Examiner further found that Schroff describes
multimeric assemblies of the DNA molecule (namely, the "concatemeric
molecule" as claimed) having the same immune system activity recited in
the claims. Id. For this reason, the Examiner determined that the claims are
anticipated by Schroff.
Appellants contend that the monomer of the claims is defined
differently than in Schroff. Appellants stated that in the claims, monomer
"refers to a segment, or subunit, of a covalently closed DNA construct,"
while in Schroff it is "is defined as a covalently closed dum[b ]bell-shaped
DNA construct, that is, it is a single molecule." Br. 8. Appellants contend
that Schroff's molecules "form high-molecular structures via the formation
of G-structures," the latter which are a "stretch of four guanine bases in a
single molecule that can associate through Hoogsteen hydrogen bonding
with guanine bases of another (second) molecule" and not via covalent
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Application 13/266,905
bonds. Id. In contrast, Appellants argue that the claim is directed to a
covalent closed DNA comprised of four DNA monomers joined together
covalently. Id. at 8-9.
Appellants further argue that "several of these dumbbell-shaped
molecules form multimeric or oligomeric assemblates (see page 4 of
Schroff)" which are "formed by intermolecular G-structures which, by
definition, means that there are no covalent bonds between the different
components of the multimeric molecule." Id. at 10.
These arguments do not persuade us that the Examiner erred.
As found by the Examiner, Schroff describes the same method as
making the claimed concatemeric molecule as disclosed in the Specification.
Final Act. 4.
The Examiner cited the following disclosure from the Specification as
describing the method of making the claimed molecule (Ans. 6):
The molecule with improved immunemodulatory properties
claimed by the present invention ... A polymeric nucleic acid
molecule should be understood as so-called high molecular
concatemer. The invented polymeric molecule can be
manufactured by a method, comprising the following steps:
- providing a 5'-phosphorylated deoxyribonucleotide
acid,
- alcohol precipitation and subsequent drying of the
precipitate at 50°C or lyophilisation of the DNA molecule at
50°C, especially in the presence of MgCb, until a dry residue is
obtained, followed by resuspension in a buffer.
- adding T4-DNA-ligase, thereby producing a reaction
mixture, and
- incubation of the reaction mixture at 37°C for at least
30 minutes.
Spec. ,r 11.
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Application 13/266,905
In comparison, the Examiner cited Schroff s method of making its
multimeric molecule. Ans. 6.
The present invention solves the object by providing a
multimeric non-coding nucleic acid molecule. The multimeric
molecule can be produced by means of a method comprising
the following steps:
- providing a 5'-phosphorylated oligodeoxyribonucleic
acid sequence in water,
- lyophilizing until a dry residue is obtained, followed by
resuspending in a buffer solution,
- adding T4 DNA ligase, thereby forming a reaction
mixture, and
- incubation the reaction mixture at 37°C for at least 30
minutes.
Schroff 3:29-4:7.
As can be readily seen by comparing the two methods, both methods
provide a phosphorylated deoxyribonucleotide, lyophilize it, add a T4-DNA-
ligase, and incubate the reaction until a product is formed. Because both
methods are the same, including using a DNA comprising the same
"deoxyribonucleotide" of claims 1 and 2, including a sequence of claim 2,
(Schroff 5: 15-18) and a T4 DNA ligase, the Examiner had reasonable
factual basis to find that the resulting molecule produced by the ligase
reactions would be the same. As held in In re Best, 562 F.2d 1252, 1255
(CCPA 1977):
Where, as here, the claimed and prior art products are identical
or substantially identical, or are produced by identical or
substantially identical processes, the PTO can require an
applicant to prove that the prior art products do not necessarily
or inherently possess the characteristics of his claimed product.
Whether the rejection is based on "inherency" under 35 U.S.C.
§ 102, on "prima facie obviousness" under 35 U.S.C. § 103,
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Application 13/266,905
jointly or alternatively,[] the burden of proof is the same, and its
fairness is evidenced by the PTO' s inability to manufacture
products or to obtain and compare prior art products.
Furthermore, not only are the methods the same, but Schroff also
describes the resulting molecule as multimeric, namely formed from several
different monomers:
Most surprisingly, the order of the above-mentioned steps
results in a multimeric molecule which is better suited for use in
modulating the activity of the human or animal immune system
than the molecules of the prior art. A multimeric molecule in
the meaning of the invention is essentially a deoxyribonucleic
acid molecule, said nucleic acid molecule preferably having a
length of at least 100 nucleotides, more preferably 200,
especially preferably more than 300. While EP 1 196 178
discloses molecules which, in view of their stem-loop structure,
can be referred to as monomers, the method according to the
invention provides molecules wherein a number of such stem-
loop monomer structures assemble into multimeric or
oligomeric structures.
Schroff 4:9--19 (emphasis added). Thus, whether Schroff defines monomer
differently than in the Specification is not dispositive because Schroff still
describes a multimeric molecule, i.e., more than one monomer.
Once "the PTO shows sound basis for believing that the products of
the applicant and the prior art are the same, the applicant has the burden of
showing that they are not." In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990).
Having satisfied this burden by showing that the methods are the same, the
burden shifted to Patent Owner to show the resulting molecule is different.
Appellants have not factually distinguished the claimed concatemer
from the multimeric molecule of Schroff, particularly when a DNA
comprising the same sequence as claimed is used a starting material and
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Application 13/266,905
ligated using the same T4 DNA ligase method as described in the
Specification.
Appellants' argument that Schroff' s molecule is held together by G-
structures and not covalent bonds are required by claim 1 is not supported by
the evidence. Br. 8, 10. The structures shown on page 2 and 3 of Schroff' s
drawings are shown as covalently closed circles, as is the molecule depicted
in Figure 1 of the Specification and claimed. Indeed, Schroff expressly
describes its molecules as covalently closed nucleic acid molecules. Schroff
2:7-9, 5:22-28, 55 (claim 42). Schroff also describes making circular and
multimeric DNA molecules. Schroff 25:5-7. The Specification describes
its claimed concatemeric molecule as comprising "covalently bound
monomer units, which are in their entirety circularly closed." Spec. ,r 12.
We agree that Schroff describes G-structures and G-quartets. Schroff
14, 16-17. However, Appellants have not identified where Schroff teaches
that the covalent bonds produced by its T 4 ligase, resulting in a "covalently
closed chain of deoxyribonucleoside residues" (Schroff 5 :23-24, 55 ( claim 4
(n. 2))), are replaced by G-structures held together by Hoogsteen base pair
bonds as asserted (Br. 8). Appellants refer to Schroffs disclosure of
"competition between intra- and intermolecular G-structures" (id. at 10).
Appellants, however, do not explain how the existence of such structures,
which result in base pairing within one molecule or base pairing with a
second, third molecule, etc., negates the teachings in Schroff of a covalently
2 "4. The molecule according to any of the preceding claims, characterized
in that the molecule comprises a partially single-stranded, covalently closed
chain of deoxyribonucleoside residues." Schroff 55.
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Application 13/266,905
closed circle. Appellants appear to be arguing that the existence of G-
structures precludes covalent bonding between the DNA molecules
subjected to ligase (id. at 10), but provided no objective evidence to support
this position. An argument made by counsel in a brief does not substitute for
evidence lacking in the record. Estee Lauder, Inc. v. L 'Orea!, S.A., 129 F.3d
588, 595 (Fed. Cir. 1997).
In addition, Appellants have not established that the disclosure in
Schroff beginning at page 14, where G-structures are described, utilizes the
same multimeric molecule produced by the ligase reaction described on
pages 3--4 of Schroff.
Appellants state there are covalent bonds in the so-called dumbbell-
shaped molecule shown in Schroffs drawings (Br. 10), but challenge that
covalent bonds are formed when the monomers "assemble into multimeric
or oligomeric structures" (Schroff 4: 18-19).
Appellants have not provided adequate evidence to support this
argument.
Schroff teaches:
Another preferred embodiment of the invention envisages that
the molecule comprises a partially single-stranded, covalently
closed chain of deoxyribonucleoside residues. It is the partially
single-stranded, covalently closed chain of deoxyribonucleoside
residues within the assembled oligomeric or polymeric structure
of the molecule that is responsible for prolonged effective
activity of the molecule in a target organism wherein it has been
incorporated.
Id. at 5:22-28 (emphasis added). Thus, despite Appellants' argument about
the existence of G structure as indicating that the molecule is not covalently
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linked, Schroff teaches a covalently linked polymeric structure. Appellants
have not addressed this express teaching in Schroff.
For the foregoing reasons, the anticipation rejection of claim 1 is
affirmed. Claims 2--4, 12, 14, 16-18, 20, 21, and 25-32 were not argued
separately and fall with claim 1.
OBVIOUSNESS REJECTION
The Examiner rejected the claims as obvious based on Schroff. Final
Act. 5.
The Examiner found claims 25-32 to be product-by-process claims,
namely, where the claimed concatemeric molecule is produced by the
process recited in the claims. Id. The Examiner found the claims
indistinguishable from the molecule produced by Schroff for the reasons
discussed above. Id.
Appellants make the same unpersuasive arguments as they did for
claim 1. Br. 11.
Claims 16-18 and 20-23 are directed to methods of using the
molecule of claim 1 to modulate the immune system ( claim 16) and treat a
cell growth disorder in a subject ( claim 22). Schroff discloses that its
molecules are suitable for stimulation the immune system (Schroff 5: 10-12)
and to treat cell growth disorders (id. at 10:30-11: 1 ). A preponderance of
the evidence, thus, supports the Examiner's finding the claims are made
obvious by Schroff.
Appellants contend that there is "no disclosure or suggestion of such
methods, nor the use of the molecules as claimed for any method" (Br. 12),
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but failed to address the explicit disclosure in Schroff where such methods
are described.
Appellants argue that final rejection was premature and should be
withdrawn. Id. at 11. This issue is not appealable, but rather is petitionable
to the USPTO Director. See 37 C.F.R. § 1.181; MPEP § 1002.02(c)(3)(a).
SUMMARY
The rejection of claims 1--4, 12, 14, 16-18, 20, 21, and 25-32 under
pre-AIA 35 U.S.C. § 102(b) is affirmed.
The rejection of claims 1--4, 12, 14, 16-18, 20-23, and 25-32 under
pre-AIA 35 U.S.C. § 103(a) is affirmed.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
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