Ex Parte Haseltine et al

Patent Trial and Appeal Board

Aug 28, 2018

12941761 (P.T.A.B. Aug. 28, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/941,761 11/08/2010
20350 7590 08/30/2018
KILPATRICK TOWNSEND & STOCKTONLLP
Mailstop: IP Docketing - 22
1100 Peachtree Street
Suite 2800
Atlanta, GA 30309
UNITED ST A TES OF AMERICA
Cynthia A. Haseltine
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.
023070-125300US 1413
EXAMINER
SALMON, KATHERINE D
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
08/30/2018 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):
ipefiling@kilpatricktownsend.com
KTSDocketing2@kilpatrick.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CYNTHIA A. HAS EL TINE and
STEPHEN C. KOWALCZYKOWSKI 1
Appeal2017-008672
Application 12/941, 7 61
Technology Center 1600
Before ULRIKE B. JENKS, JAMES A. WORTH, and RYAN H. FLAX,
Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision under 35 U.S.C. § 134(a) involving claims directed
to a method for binding a multimeric protein with a single stranded DNA.
All pending claims are on appeal as rejected under 35 U.S.C. § 103. We
have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
1 Appellants identify the Real Party in Interest as "Regents of the University
of California." Appeal Br. 3. Herein we reference the Specification of Nov.
8, 2010 ("Spec."); the Final Office Action of July 21, 2015 ("Final Action");
the Appeal Brief of Jan. 20, 2016 ("Appeal Br."); the Examiner's Answer of
Aug. 2, 2016 ("Answer"); andReplyBriefofOct. 3, 2016 ("Reply Br.").
Appeal2017-008672
Application 12/941, 7 61
STATEMENT OF THE CASE
The Specification states, "[s]ingle-stranded DNA (ssDNA) binding
proteins (SSBs) are essential in most intracellular interactions that involve
DNA, including replication, repair, and recombination." Spec. ,r 5. The
Specification further states,
The crenarchaeon S. [ Sulfolobus] solfataricus is a
hyperthermophic aerobe that grows in sulfur hot springs. Its
optimal growth conditions are temperatures of 70-90°C and pH
levels from 2-4. The entire genome of the organism was
sequenced and published in 2001. She et al., "The complete
genome of the crenarchaeon Sulfolobus solfataricus P2," Proc.
NatlAcad Sci (USA) 98:7835-7840 (2001). In 2001, Wadsworth
and White reported the identification of a single-stranded DNA
(ssDNA) binding protein (SSB) from S. solfataricus.
Wadsworth and White, Nuc Acids Res 29(4):914-920 (2001).
The work from this laboratory indicates that the S SB is present
as a monomer.
Id. ,r 21. The Specification further states,
The S. solfataricus ssDNA binding protein ("SsoSSB protein")
consists of 148 amino acids with 4 7% identity and 69% similarity
(that is, that the residues are either identical or conservative
substitutions for one another) to the SSB of another
crenarchaeon, A. pernix. The amino acid sequence of SsoSSB
(SEQ ID NO: 1) is shown in Figure 8A, and is available in the
National Center for Biotechnology Information Entrez database
under accession numbers NP 343725 and AAK42515.
Id. ,r 22. And further, "the monomers of S. solfataricus ssDNA binding
protein ('SsoSSB protein') associate with one another to form a complex,
referred to herein as 'multimeric protein' or a 'multimer') in solution and it
is the complex, or multimeric protein, that is functional in binding ssDNA."
Id. ,I 23.
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Application 12/941, 7 61
Independent claim 6 is representative and is reproduced below:
6. A method for binding a multimeric protein with a
single stranded DNA, said method comprising:
(1) recombinantly producing a polypeptide that has at
least 95% sequence identity to SEQ ID NO: 1
(2) purifying the polypeptide; and
(3) contacting the purified polypeptide with a single
stranded DNA under conditions permissible for the polypeptide
to form a multimeric protein such that the multimeric protein
binds the single stranded DNA.
Appeal Br. 11 (Claims Appendix).
The following rejection is appealed:
Claims 6, 9-11, and 17-18 stand rejected under 35 U.S.C. § 103(a)
over Nielson, 2 Carpentieri, 3 She, 4 and GenBank. 5 Final Action 2.
DISCUSSION
Only those arguments made by Appellants in the Appeal Brief and
properly presented in the Reply Brief have been considered in this Decision;
arguments not so-presented in the Brief are waived. See 37 C.F.R.
§ 4I.37(c)(l)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1474
2 US 5,449,603 (issued Sept. 12, 1995) ("Nielson").
3 Floriana Carpentieri et al., Physical and Functional Interaction between
the Mini-chromosome Maintenance-like DNA H elicase and the Single-
stranded DNA Binding Protein from the Crenarchaeon Sulfolobus
solfataricus, 277(14) J. BIO. CHEM. 12118-127 (2002) ("Carpentieri").
4 Qunxin She et al., The complete genome of the crenarchaeon Sulfolobus
solfataricus P2, 98 PNAS 7825--40 (2001) ("She").
5 She et al., Single-stranded DNA binding protein (SSB) [Sulfolobus
solfataricus], NCBI (July 5, 2001), Accession No. AAK42515,
http://www.ncbi.nlm.nih.gov/entrez/viewer.fcgi?13815667:0LD13:1039505
("GenBank").
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Application 12/941, 7 61
(BP AI 2010) (informative) ("Any bases for asserting error, whether factual
or legal, that are not raised in the principal brief are waived."). "[T]he
examiner bears the initial burden, on review of the prior art or on any other
ground, of presenting a prima facie case of unpatentability. If that burden is
met, the burden of coming forward with evidence or argument shifts to the
applicant." In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007). "In determining
whether the subject matter of a patent claim is obvious, neither the particular
motivation nor the avowed purpose of the patentee controls. What matters is
the objective reach of the claim. If the claim extends to what is obvious, it is
invalid under § 103." Id. at 419. It is obvious to those skilled in the art to
substitute one known equivalent for another. See In re Omeprazole Patent
Litigation, 483 F.3d 1364, 1374 (Fed. Cir. 2007) ("[T]his court finds no ...
error in [the] conclusion that it would have been obvious to one skilled in the
art to substitute one ARC [alkaline reactive compound] for another.").
Where . . . the claimed and prior art products [ or methods] are
identical or substantially identical ... the PTO can require an
applicant to prove that the prior art products [ or methods] do not
necessarily or inherently possess the characteristics of his
claimed product [ or method]. Whether the rejection is based on
'inherency' under 35 U.S.C. § 102, on 'prima facie obviousness'
under 35 U.S.C. § 103, 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.
In re Best, 562 F.2d 1252, 1255 (CCPA 1977) (citations and footnote
omitted). Claim "terms [that] merely set forth ... a property inherent in, an
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Application 12/941, 7 61
otherwise old composition [ or method step] ... do not differentiate the
claimed composition [or method] from those known in the prior art." In re
Pearson, 494 F.2d 1399, 1402 (CCPA 1974). "[I]t is not required ... that
the prior art disclose or suggest the properties newly-discovered by an
applicant in order for there to be a prima facie case of obviousness." In re
Dillon, 919 F.2d 688, 697 (Fed. Cir. 1990); see also Atlas Powder Co. v.
Ireco, Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) ("[T]he discovery of a
previously unappreciated property of a prior art composition, or of a
scientific explanation for the prior art's functioning, does not render the old
composition patentably new to the discoverer."). Mere recognition of latent
properties in the prior art does not render nonobvious an otherwise known
invention. In re Prindle, 297 F.2d 251,254 (CCPA 1962).
"Where the prior art contains 'apparently conflicting' teachings (i.e.,
where some references teach the combination and others teach away from it)
each reference must be considered 'for its power to suggest solutions to an
artisan of ordinary skill ... consider[ing] the degree to which one reference
might accurately discredit another."' Medichem S.A. v. Rolabo S.L., 437
F.3d 1157, 1165 (Fed. Cir. 2006) (quoting In re Young, 927 F.2d 588, 591
(Fed. Cir. 1991)).
Although a reference that teaches away is a significant factor to
be considered in determining unobviousness, the nature of the
teaching is highly relevant, and must be weighed in substance.
A known or obvious composition [ or method] does not become
patentable simply because it has been described as somewhat
inferior to [ or different than] some other product [ or method] for
the same use.
In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
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The Examiner determined that all pending claims would have been
obvious over Nielson, Carpentieri, She, and GenBank. Final Action 2-15
and Answer 2-9 (collectively citing Nielson 2:17-22, 3:5-8, 3:10-15, 8:5-
21, 10:27-54, 13-14, 15:66-68, 16:1-3, 18-20; Carpentieri 12119; She
7835, 7837; and GenBank generally). Significantly, the Examiner
determined that the "conditions permissible" limitation of the claims, which
is the limitation at issue on appeal, was not expressly defined in the
Appellants' Specification or claims as any specific set of conditions and was
taught and suggested by, and obvious over, Nielson's disclosure of
( essentially conventional) hybridizing conditions for SSB and ssDNA
admixtures at columns 8, 10, and 19 of the reference. See Answer 6, 8. The
Examiner determined "it was well within the knowledge of the ordinary
artisan the conditions that would permit mulitmerization." Id. at 6; see also
Declaration Under 37 C.F.R. § 1.132 of Dr. Kowalczykowski ,r 7 (Aug. 29,
2014) ("Kowalczykowski Deel.") ("a person possessing ordinary skill in the
pertinent art would have no or little difficulty to determine whether or not
any particular conditions are permissible for the formation of a multimeric
protein from its monomeric polypeptide."). We discern no error in the
Examiner's determinations and adopt the Examiner's findings of fact and
rationale. See Final Action 2-15; Answer 2-9. We address Appellants'
arguments below.
Appellants' arguments can be summarized as follows: ( 1) because the
skilled artisan would have believed SsoSSB binds to ssDNA as a monomer,
the claim limitation "contacting the purified polypeptide with a single
stranded DNA under conditions permissible for the polypeptide to form a
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nmltimeric protein such that the multimeric protein binds the single stranded
DNA" is not taught or suggested by the cited prior art combination; and (2)
the conditions disclosed in the prior art combination are not sufficiently
detailed to know if they are "conditions permissible," as claimed.
Appellants' arguments are not persuasive. We address them more
specifically below.
Appellants argue Nielson does not disclose "any SSB proteins from S.
solfataricus P2 or any particular sequence similar to SEQ ID NO: 1," as
claimed, but concede that "[t]he She reference provides the complete
genome of S. solfataricus P2, including a single stranded DNA binding
protein (SSB) the amino acid sequence of which is apparently provided in
AAK42515 and identical to SEQ ID NO: 1." Appeal Br. 5; see also
GenBank ( disclosing SEQ ID NO: 1 as originally identified in She).
There is no dispute that the prior art combination teaches the
advantages of using an SSB in binding ssDNA in DNA analysis or how to
do so. There is likewise no dispute that the exact SSB of SEQ ID NO: 1 was
known. Nielson discloses SSB "decreases the amount of nonspecific
hybridization between nucleic acids." Nielson 3:5-9. Likewise, She
discloses Sso2364, the 148 aa sequence of SEQ ID N0:1 (as detailed in
GenBank), may be required for DNA replication and repair. She 7837.
Nielson discloses the presence of SSB has "broad application to all
procedures involving DNA hybridization and, specifically, increasing the
specificity and hybridization in PCR using SSB, specifically Eco SSB."
Nielson 3: 10-36. Nielson and She suggest that SsoSSB and Eco SSB have
similar characteristics and provide similar advantages in DNA analysis.
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Nielson also suggests that E. coli and Sulfolobus proteins are similarly useful
and compatible. See id. at 14:4--33 (discussing heat-stable DNA
polymerases from E. coli and Sulfolobus acidacaldarius as useful for PCR to
accomplish primer synthesis). It is obvious, as is the case here with SSB
proteins, to substitute one known equivalent for another. See In re
Omeprazole, 483 F.3d at 1374.
Appellants further argue that, while Carpentieri is cited by the
Examiner as teaching that S. solfataricus SSB is "an abundant protein that
exists as a monomer in solution and multimerizes upon DNA binding ( e.g.,
binding to a single stranded DNA)," Carpentieri's teachings are based on the
work published by Wadsworth, 6 but the same group of researchers later took
an opposite position on this issue. Appeal Br. 5---6 ( citing Cubeddu 1 and
Cubeddu 2; 7 also citing the Kowalczykowski Deel.). Appellants contend,
based on the Cubeddu references, "the artisan would most likely perform the
6 Ross I.M. Wadsworth & Malcolm F. White, Identification and properties
of the crenarchaeal single-stranded DNA binding protein from Sulfolobus
solfataricus, 29(4) NUCLEIC ACIDS RES. 914--20 (2001) ("Wadsworth")
(submitted by Appellants at Appeal Br. 13 (Evidence Appendix).
7 Liza Cubeddu et al., Structural andfunctional characterisation of
Sulfolobus Solfataricus SSB and its interaction with DNA, F ASEB Summer
Research, Poster Abstract (2002) ("Cubeddu 1 ") ( authorship includes
Wadsworth and White); Liza Cubeddu et al., Structural and calorimetric
studies of an archaeal single-stranded DNA binding protein, partial internet
address provided as "http://www.microcalorimetry.com/Dublin
%20conference%202002/white%20short%20tal...," indicated as printed Oct.
15, 2002 ("Cubeddu 2) (authorship includes Wadsworth and White).
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SSB protein and ssDNA binding assay under a set of reaction conditions in
favor of the monomeric formation of the SSB protein." Id. at 7. 8
Appellants also argue that the Examiner's position that the processing
conditions of Nielson, which Appellants concede includes a temperature
range overlapping that described in the Specification as suitable for forming
SSB multimers, satisfies the "conditions permissible" limitation is incorrect.
Appeal Br. 8. Specifically, Appellants direct us to the Kowalczykowski
Declaration's statement suggesting that many factors constitute the claimed
"conditions permissible" and temperature is just one such condition. Id.
Appellants argue Nielson does not provide adequate details of other factors
that are relevant, contending that under the doctrine of inherency, this lack
of detail cannot confirm that the proteins would be either monomeric or
multimeric. Id.
As already indicated, Appellants' arguments are not persuasive.
While somewhat relevant, whether or not the statements of Carpentieri
confirming that SsoSSB binds to ssDNA as a multimer would have been
8 Appellants also cite the Spec. ,r 63 in support of this position. This portion
of the Specification states:
Examination of the SsoSSB protein in solution revealed that it
was present in three distinct species: monomeric, dimeric, and
tetrameric forms, at 18 kDa, 36 kDa, and 62 kDa, respectively
(Figure 4a). As demonstrated by a representative elution profile
(Figure 4b ), the composition of the purified material was
primarily tetrameric, while somewhat less dimeric protein was
present. A significantly smaller quantity of the monomeric form
of SsoSSB protein was observed.
Thus, there appears to be some impurity in the protein solution of the
invention regarding its subunit assembly.
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relied upon by the skilled artisan as proof that such a result is expected, what
matters in view of the claim language is not an identification of a guaranteed
multimeric result, but the provision of conditions permissible for such a
result to be reasonably expected to occur. See In re O'Farrell, 853 F.2d
894, 903---04 (Fed. Cir. 1988) ("Obviousness does not require absolute
predictability of success .... For obviousness under§ 103, all that is
required is a reasonable expectation of success."). If such conditions are
provided when a purified protein of SEQ ID NO: 1 is contacted with ssDNA,
whether or not the skilled artisan would have explicitly known the protein
would be in a multimeric configuration is not determinative of obviousness.
See In re Dillon, 919 F.2d at 697; In re Prindle, 297 F.2d at 254.
Regarding just what constitutes "conditions permissible for the
polypeptide to form a multimeric protein," as claimed, the Specification is
not explicit on the scope of such parameters, but the Kowalczykowski
Declaration states:
From the perspective of a person of skill in the art of protein
chemistry, however, the consideration of these relevant factors
and their potential effect on multimeric protein formation is not
so complex as to present any significant difficulties. For
instance, one possessing an ordinary level of skill in the pertinent
research field would appreciate that, in general, a pH range of
about 5.5 to 9 is suitable for monomeric units to form a
multimeric protein and remain in this functional state. Similarly,
a temperature range of about 10°C to 80°C, and a monovalent
salt (e.g., Na+ or K +, chloride or acetate) concentration of
about 5 mM to 500 mM typically also containing 1 mM to 20
mM Mg +2 salt, would be suitable for multimeric protein
formation. In most cases, the use of detergents and salt may
limit nonspecific aggregation or precipitation, but the presence
of detergents may interfere with the formation of a multimeric
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protein when the detergent (e.g., Triton X-100 or Tween 20/80)
concentration is high, e.g., above 0.1 %. In other words, a
person possessing ordinary skill in the pertinent art would have
no or little difficulty to determine whether or not any particular
conditions are permissible for the formation of a multimeric
protein from its monomeric polypeptide.
Kowalczykowski Deel. ,r 7 ( emphasis added). Thus, the person of ordinary
skill would understand that the relevant conditions include a pH of about
5. 5-9, a temperature of about 10-80°C, a salt concentration of about 5-500
mM, and usually limiting a detergent concentration to 0.1 % or less.
However, the evidence establishes that determining such conditions would
present little or no difficultly to the skilled artisan.
The Examiner did not cite Carpentieri for its teachings of specific
processing steps, but for its identification of the SSB protein from S.
solfataricus and the property of SsoSSB becoming a multimer upon binding
to ssDNA. Final Action 4. This amounts to a recognition that a certain
functional result occurs. For processing conditions, the Examiner cited
Nielson. Id. at 2-3.
Nielson discloses DNA hybridization (PCR) processing conditions
using SSB proteins. See Nielson 6:21-23 ("In all embodiments described
herein there is a single stranded nucleic acid binding protein (SSB) included
in the hybridization reaction admixture."). Significantly, Nielson discloses
that to gain "the benefits of including SSB in probe-target hybridization,"
such hybridization conditions include a temperature range of 30-100°C, a
pH range of 4--9, and salt concentrations of 500 mM; but, in any event,
"[ m ]ethod[ s] for optimizing hybridization conditions for a given
hybridization reaction admixture [were] well known in the art." Id. at 8:6-
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10, 9:62----67 (quoted portion), 10:28-53 (quoted portion), 13:7-14:68,
18:50-52, 19:23-20:24. Nielson does not indicate that Triton X-100 or
Tween 20/80, identified in the Kowalczykowksi Declaration as influencing
the interaction, are needed in such processes. Therefore, we conclude, as did
the Examiner, that Nielson teaches and suggests "contacting the purified
polypeptide with a single stranded DNA under conditions permissible for the
polypeptide to form a multimeric protein such that the multimeric protein
binds the single stranded DNA," as claimed, in sufficient detail to render the
limitation obvious.
We conclude the Examiner has established that the methods disclosed
by Nielson for using an SSB in PCR techniques and DNA hybridization are
"conditions permissible" for forming a multimeric protein for the protein of
SEQ ID NO: 1 to bind ssDNA. Appellants have not shown that Nielson's
methods would not do so. See In re Best, 562 F.2d at 1255. Appellants'
mere recognition of latent properties in the cited prior art combination's
methods, i.e., that Nielson's PCR techniques would result in an SsoSSB
multimer binding to ssDNA, does not render nonobvious the otherwise
obvious method. See In re Prindle, 297 F .2d at 254.
For the reasons above, we conclude the Examiner's determinations of
obvious are sound and are unpersuaded by Appellants' arguments.
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SUMMARY
The obviousness rejection under 35 U.S.C. § 103 is affirmed.
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)(l)(iv).
AFFIRMED
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