Ex Parte Verma et al

Patent Trial and Appeal Board

May 11, 2016

11918841 (P.T.A.B. May. 11, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111918,841 11/06/2009
28289 7590 05/13/2016
THE WEBB LAW FIRM, P,C
ONE GATEWAY CENTER
420 FT. DUQUESNE BL VD, SUITE 1200
PITTSBURGH, PA 15222
FIRST NAMED INVENTOR
Santosh K Verma
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.
4544-073622 7717
EXAMINER
POPA, ILEANA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
05/13/2016 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):
patents@webblaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SANTOSH K. VERMA, NISHI RAJ SHARMA, V ALLURIP ALLI
VINOD KUMAR, ARABINDA CHAUDHURI,
DEBI P. SARKAR, PRASHANT MANI, ANUJA KRISHNAN,
BATHULA SURENDAR REDDY, and RAJANDRA P. ROY
Appeal2014-002659
Application 11/918,841
Technology Center 1600
Before DEMETRA J. MILLS, MELANIE L. McCOLLUM, and
JOHN G. NEW, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness and obviousness-type double patenting. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
Appeal2014-002659
Application 11/918,841
STATEMENT OF CASE
The Specification discloses a process for producing a modified
reconstituted Sendai viral envelope (virosome) specific for drug and/or gene
delivery to cells, particularly liver cells. Spec. 1.
The following claim is representative.
7. A process for producing a reconstituted viral envelope comprising the
steps of:
i. adding a reducing agent to a Sendai virus to reduce a
hemagglutinin-neuraminidase ("HN") protein;
ii. removing the reducing agent by dialysis;
iii. solubilizing the reduced Sendai virus with a detergent to obtain a
solution containing an insoluble-reduced HN protein;
iv. centrifuging the solution to separate the insoluble-reduced HN
protein and to form a supernatant;
v. adding a histidylated lipid to the supernatant;
vi. adding a therapeutic agent after the addition to the lipid wherein
the therapeutic agent is a gene or a drug;
vii. removing the detergent from the supernatant; and
viii centrifuging the supernatant to obtain a His lipid F-virosomes with
the therapeutic agent contained therein.
Cited References
Sarkar et al. us 5,683,866 Nov. 4, 1997
("Sarkar")
Saeki et al., Development and Characterization of Cationic Liposomes
Conjugated with HVJ (Sendai Virus): Reciprocal Effect of Cationic Lipid for
In Vitro and In Vivo Gene Transfer, 8 Human Gene Therapy 2133-2141
(1997) ("Saeki").
Kim and Park, Gene transfection by quantitatively reconstituted Sendai
envelope proteins into liposomes, 9 Cancer Gene Therapy 173-177 (2002)
("Kim").
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Application 11/918,841
Kumar et al., Single histidine residue in head-group region is sufficient to
impart remarkable gene transfection properties to cationic lipids: evidence
for histidine-mediated membrane fusion at acidic pH, 10 Gene Therapy
1206-1215 (2003) ("Kumar").
Grounds of Rejection
1. Claims 7-11 are rejected on the ground of nonstatutory
obviousness-type double patenting as being unpatentable over
claims 1-22 of U.S. Patent No. 5,683,866 in view of both Kim and
Kumar.
2. Claims 7-11 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Kim in view of both Saeki and Kumar.
FINDINGS OF FACT
The Examiner's findings of fact are set forth in the Answer at pages
3-19. The following fact is highlighted.
1. Figure 2 of Appellants' Specification is reproduced below.
PREPARATION OF HlSTlDYLATED F-VIROSOl\fE5
{Wrrn St.IGUT MOD!J>''ICA UON or RAMAN I ct. "" f'ROCS:SS Fm~ PROm.lt:iN!i;)., TA fl:~.~ 1"[ ll G mg, (I 9'n} 1;:,s. PA; l;;~T i;..t;sz;!l.!il$.
Fig-, 2
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Application 11/918,841
Figure 2 is a schematic of the claimed process of the preparation of
histidylated F-virosomes.
PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
"In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant." In re Rijckaert, 9 F.3d 1531, 1532 (Fed.
Cir. 1993) (citations omitted).
"The combination of familiar elements according to known methods
is likely to be obvious \'l1hen it does no more than yield predictable results."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). Moreover, "[w]hen
there is a design need or market pressure to solve a problem and there are a
finite number of identified, predictable solutions, a person of ordinary skill
has good reason to pursue the known options within his or her technical
grasp. If this leads to the anticipated technical success, it is likely the
product not of innovation but of ordinary skill and common sense." KSR,
550 U.S. at 421.
Rejections 1 and 2- Double Patenting and Obviousness
As both of these rejections present similar issues, we address both of
the standing rejections together. Kim and Kumar are commonly cited in
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Application 11/918,841
both rejections 1 and 2. Appellants do not present separate arguments for
individual claims, therefore we select claim 7, as representative of each
separate rejection. Claim 7 does not recite a specific cell type to which the
reconstituted viral envelope is delivered.
Regarding Obviousness-type Double Patenting Rejection 1
The Examiner finds that Sarkar (Claim 1) discloses each of the
claim 7 steps (Ans. 3), except Sarkar fails to disclose a step of "adding a
histidylated lipid" (id.). Kim is relied on for incorporating a Sendai viral
envelope protein in liposomes. Ans. 3. The Examiner relies on Kumar for
teaching that "incorporating histidylated lipids into liposomes [for gene
delivery] enhances their transfection efficiency in HepG2 cells (Abstract;
p.1208, Scheme 1 )."(Id.) The Examiner concludes that
It would have been obvious to one of skill in the art, at the time
the invention was made, to modify the patent claims by further
adding lipids including histidylated lipids such as that taught by
Kumar et al. during Dl'-Jii~ encapsulation step, \'l1ith a reasonable
expectation of success .... One of skill in the art would have
been motivated to use such histidylated lipid in order to further
enhance transfection efficiency of the Sendai virosomes taught
by the patent claims.
Ans. 3--4.
Regarding Obviousness Rejection 2
The obviousness rejection replaces Sarkar and Kim in the
obviousness-type double patenting rejection with Kim alone. The Examiner
finds that Kim teaches or suggests each element claimed, except a step of
"adding a histidylated lipid." Ans. 5. Saeki and Kumar are relied upon by
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Application 11/918,841
the Examiner to provide the motivation to include histidylated lipids in the
virosomes of Kim. Ans. 14. Therefore, as in the obviousness-type double
patenting rejection, the Examiner relies on Kumar for teaching a step of
"adding a histidylated lipid." Ans. 5.
ANALYSIS
With respect to each of these rejections, we agree with the Examiner's
fact finding, statement of the rejection, and responses to Appellants'
arguments as set forth in the Answer. We find that the Examiner has
provided evidence to support a prima facie case of obviousness. We provide
the following additional comment to the Examiner's argument set forth in
the Final Rejection and Answer.
Appellants do not challenge the specific process steps of Sarkar, claim
1 (and 2-22) with respect to the obviousness-type double patenting rejection.
Instead, in both the obviousness-type double patenting rejection and the
obviousness rejection, Appellants contend that
Kim does not disclose or suggest inclusion of histidylated lipids
in Sendai virus envelopes. Kim teaches that virosomes formed
from Sendai virus (including both F proteins and HN proteins)
are more efficient at transfection than pure cationic liposomes
in vitro in HEK-293 (kidney) cells (Kim, Figs. 2B and 4).
Moreover, Kim teaches that virosomes that lack HN protein
exhibit poor transfection (Kim, Fig. 2B).
Br. 12. Appellants argue that, "[based] on the results of Kim, specifically
that virosomes that lack HN protein exhibit poor transfection efficiency, one
of skill in the art would take from Kim that HN protein is desirable in a
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Application 11/918,841
virosome. This directly teaches away from reduction and removal of HN
proteins, as provided in the presently claimed methods." Br. 12.
The Examiner responds, arguing that,
At the time of filing, Sendai virosomes lacking HN protein but
including F protein (i.e., Sendai F virosomes) were known and used in
the art as efficient transfection agents, for example by Kim et al. At
the time of filing, enhancing the transfection efficiency of Sendai F
virosomes by including histidylated lipids was taught by the combined
teachings of Saeki et al. and Kumar et al.
Thus, one of skill in the art would [have] found it obvious to
obtain Sendai F virosomes comprising histidylated lipids with the
expectation that including histidylated lipids would improve
transfection efficiency over Sendai F virosomes not comprising
histidylated lipids.
Ans. 8. Pointing to data in Figs. 2 and 4 of Kim, the Examiner further finds
that
There is no basis in Kim et al. for drawing such a conclusion
as there is no teaching in the entire reference that F-virosomes are
poor transfection agents. The appellant[ s] did not point to any data or
teaching in Kim et al. indicating or suggesting that F virosomes are
not to be used because they are poor transfection agents. On the
contrary, Kim et al. specifically teach both F and F /HN virosomes as
efficient transfection agents.
Ans. 12. We agree. Appellants point to no credible data in Kim showing
that F virosomes are not to be used because they are poor transfection
agents. That fact that the F virosomes of Kim may not be as efficient
transfection agents, is not a teaching away, as the F virosomes of Kim do
achieve a level of transfection. Appellants file no Reply Brief, responding to
the Examiner's arguments regarding Figs. 2 and 4 of Kim.
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Appellants argue that, based on the teachings of Kim et al. that
virosomes lacking HN exhibit poor transfection efficiency, one of skill in the
art would understand that HN protein is desirable in a virosome, which
constitutes a teaching away from its removal. Br. 12, 16. We adopt the
Examiner's response to this argument (Ans. p. 12-14), and other arguments
set forth in the Answer and not further addressed herein, as our own.
Appellants argue that Kim teaches that pure liposomes are to be
avoided, and Kumar teaches pure liposomes, "and teaches that histidylated
lipids do not increase transfection in 293T7 (kidney) cells." Br. 10. We are
not persuaded. Kim teaches that fusogenic liposomes (virosomes) and
cationic liposomes for gene therapy applications enhance transfection
efficiency and sustain gene expression. Abstract; p. 173, col. 1. Appellants'
Brief points to no specific location in Kim indicating that the use of pure
liposomes is to be avoided1 and fails to address Kim's F-virosome
disclosures and their enhanced transfection efficiency.
Moreover, the Examiner responds, arguing that
The argument that one of skill in the art would not have
combined Kim et al. with Kumar et al. because Kumar et al.
teach pure liposomes and Kim et al. teach that pure liposomes
are to be avoided is not found persuasive. Apart from an
argument, the appellant did not provide any evidence indicating
or suggesting that teachings related to pure liposomes cannot be
extrapolated to virosomes, which are taught by the prior art as
being liposomes that carry in their membrane fusogenic viral
proteins (see Kim et al., p. 176, column 2, last paragraph).
1 Figure 4, page 175, col. 2, of Kim evidences that 1,2 -dioleoyl- 3 -C
trimethylammonium) propane (DOTAP)/cholesterol (Chol) liposomes have
some transfection efficiency at 4 hours.
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Application 11/918,841
Ans. 9-10.
Appellants argue that, "Kumar does not teach inclusion of histidylated
lipids in a virosome, and makes no predictions on the likelihood of success
in using histidylated lipids in a virosome." Br. 14. We are not persuaded.
Kumar discloses that the "[p ]resence of endosome-disrupting multiple
histidine functionalities in the molecular architecture of cationic polymers,
... has ... been demonstrated to significantly enhance their in vitro gene
delivery efficiencies." Abstract. While Kumar may not use the term
"virosome", Kumar does discuss the efficacy of lipid based non-viral gene
delivery transfection vectors including histidine functionalities. Page 1206,
col 2. The Examiner has relied on Kim for teaching fusogenic
liposomes/virosomes for gene therapy.
Furthermore, with respect to Kumar, the Examiner finds that
Kumar et al. teach that histidylated lipids and DC-Chol are
functional equivalents, both mediating the same transfection
efficiency in 293 cells. Since Saeki et al. teach that DC-Chol
greatly enhances Sendai virosomes transfection efficiency and
since Kumar et al. teach that DC-Chol and histidylated lipids
are functional equivalents with respect to 293 cell transfection,
one of skill in the art would have reasonably expected that both
would mediate the same enhanced transfection efficiency in 293
cells as compared to the PS-comprising Sendai virosomes of
Kim et al. One of skill in the art would have found it obvious
to modify the Sendai virosomes of Kim et al. by replacing PS
with histidylated lipids to achieve the predictable result of
obtaining Sendai virosomes with enhanced transfection
capabilities. The appellant did not provide any evidence to the
contrary.
Ans. 10-11. As the claim 7 process does not require a specific composition
of histidylated lipid or a specific cell type, even in the absence of Saeki,
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Application 11/918,841
Kumar provides motivation to one of ordinary skill in the art to improve or
modify the fusogenic lipid virosome of Kim using Kumar's histidylated
lipids with improved gene transfection properties used in gene therapy.
In sum, Appellants err in attacking the references individually, when
the rejection is based on a combination of references. See In re Merck &
Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Portions of the references cannot
be read in isolation, but the references must be read for what they teach in
combination with the prior art as a whole. See id. We agree with the
Examiner that Appellants appear to read several portions of the cited
references out of context, and not with an eye to what the cited references
would have suggested to one of ordinary skill in the art at the time of the
invention.
In this decision we consider only those arguments actually made by
Appellants. Arguments that Appellants could have made but chose not to
make in the Briefs have not been considered and are deemed to be \'l1aived.
See 37 C.F.R. § 41.37(c)(l)(vii).
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The double patenting rejection is affirmed for the reasons of record.
The obviousness rejection is affirmed for the reasons of record.
CONCLUSION OF LAW
The cited references support the Examiner's obviousness rejection,
and obviousness-type double patenting rejection, which are affirmed for the
reasons of record. All pending claims fall.
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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