Ex Parte Parman et al

Patent Trial and Appeal Board

Aug 10, 2016

11796631 (P.T.A.B. Aug. 10, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
111796,631 04/27/2007 Toufan Parman
23379 7590 08/12/2016
RICHARD ARON OSMAN
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.
SRI-118/US 1468
EXAMINER
530 Lawrence Expy # 332 CLARKE, TRENT R
Sunnyvale, CA 94085
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
08/12/2016 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):
RICHARD@SCI-TECH.COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TOUF AN PARMAN, REBECCA ERICKSON,
and KAREN STEINMETZ
Appeal2014-007425
Application 11/796,631 1
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW, and RYAN H. FLAX,
Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to methods of delivering intact mammalian cells to the brain
of a rat by intranasal administration. Claims 25--44 are on appeal as rejected
under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b).
We affirm-in-part.
1 The Real Party in Interest is SRI International. App. Br. 1.
Appeal2014-007425
Application 11/796,631
STATEMENT OF THE CASE
The Specification discloses administration of intact mammalian cells
to the brain (of rats) by the intranasal route, which may be useful in treating
neurodegenerative conditions such as traumatic brain injury, Alzheimer's
and Parkinson's disease. Spec. 1. The Specification indicates "the blood
brain barrier presents a significant drawback for noninvasive delivery of
cells into the brain," and the invention is directed to bypassing the BBB
(blood brain barrier) using intranasal delivery. Id. 2.
The Specification is non-specific as to precisely how the invention
bypasses the BBB, other than using intranasal administration, but discloses
that treatment with cytokines, chemokines, and/or growth factors (e.g., IGF-
1) "may increase efficiency of entry and migration of cells delivered via the
intranasal route." Id. 6. The Specification indicates that "manipulating the
immune system may [also] increase the efficiency of cell delivery." Id. The
Specification indicates, "[m]odulation and/or disruption of mucus may also
be used to enhance delivery of the cells to the brain." Id. Further, the
Specification indicates injury mimicry may also be used to induce "release
of chemotactic signaling factors that direct movement of cells to the site of
injury." Id. 7. Finally, as an example, the Specification describes
"Intranasal Delivery" as succeeding by placing rats in a supine position with
a pad inserted under the dorsal neck to extend the head back and "adding 6-
8 µl drops [of medium with or without cells] alternatively to each naris
every 2-3 minutes over a total of 20 minutes." Spec. 9.
2
Appeal2014-007425
Application 11/796,631
The appealed claims can be found in the Claims Appendix of the
Appeal Brief. Claims 25 and 39 are independent claims. Claim 25 reads as
follows:
25. A method for delivering intact mammalian cells to the brain
of a mammal, comprising administering intranasally to a rat a
suspension of viable rat neural progenitor cells, whereby the cells
bypass the blood-brain-barrier and enter the brain of the rat.
App. Br. 15 (Claims App'x). Claim 39 reads as follows:
Id. 16.
39. A method for delivering intact mammalian cells to the brain
of a mammal, comprising administering intranasally and non-
invasively by nose drops to a naris of a rat a suspension of viable
rat neural progenitor cells, whereby the cells bypass the blood-
brain-barrier and enter the brain of the rat.
The following rejections are on appeal:
Claims 25-34 and 39--42 rejected under 35 U.S.C. § 103(a) as
' ' .. .. ' Jr • ,., .. rT""l"1 1. ___...,. .. • '. ,...... unpatemao1e over lVlessma~ ana l nome. J !' ma1 Acnon "}.
Claims 25--44 rejected under 35 U.S.C. § 103(a) as unpatentable over
Messina, Thome, Ogawa,4 and Noctor. 5 Final Action 14.
2 U.S. Patent Application Pub. No. US 2005/0032209 Al (published Feb. 10,
2005) (hereinafter "Messina").
3 R.G. Thome et al., Delivery of Insulin-Like Growth Factor-I to the Rat
Brain and Spinal Cord Along Olfactory and Trigeminal Pathways Following
Intranasal Administration, 127 NEUROSCIENCE 481-96 (2004) (hereinafter
"Thome").
4 Y. Ogawa et al., Transplantation of In Vitro-Expanded Fetal Neural
Progenitor Cells Results in Neurogenesis and Functional Recovery After
Spinal Cord Contusion Injury in Adult Rats, 69 J. NEUROSCIENCE RESEARCH
925-33 (2002) (hereinafter "Ogawa").
5 Stephen C. Noctor et al., Dividing Precursor Cells of the Embryonic
Cortical Ventricular Zone Have Morphological and Molecular
3
Appeal2014-007425
Application 11/796,631
Except where otherwise indicated, we adopt the Examiner's findings
of fact and reasoning regarding the scope and content of the prior art (see
generally Final Action and Ans.). For emphasis, we highlight the following:
FINDINGS OF FACT
FPL Messina's disclosure is directed to and teaches "[c]ells derived
from postpartum umbilicus and placenta [and p ]harmaceutical compositions,
devices and methods for the regeneration or repair of neural tissue using the
postpartum-derived cells." Messina Abstract; see also Final Action 9
(discussing Messina).
FF2. Messina disclosed using stem cells (and "in certain
embodiments, ... neural progenitor" cells) recovered "by perfusion of the
placenta or collection from umbilical cord blood," which have "the ability to
differentiate into an array of neural cell lineages" for "in vivo cell-based
therapy," including treatment of neurodegenerative conditions, such as brain
trauma, or chronic/progressive neurodegenerative conditions, such as
Alzheimer's disease. Messina i-fi-19-10, 17, 21-23, and 58; see also Final
Action 9 (discussing Messina).
FF3. Messina disclosed treating patients or subjects, including
animals generally, mammals more specifically, and humans most
specifically, and using a pharmaceutically acceptable carrier (such as PBS)
for the treating cells, within the scope of reasonable medical judgment.
Messina i-fi-151-52 and 58; see also Final Action 9-10 (discussing Messina).
Characteristics of Radial Glia, 22 J. NEUROSCIENCE 3161-73 (2002)
(hereinafter "N octor").
4
Appeal2014-007425
Application 11/796,631
FF4. Messina disclosed,
The cells of the invention may be surgically implanted, injected,
delivered (e.g., by way of a catheter or syringe), or otherwise
administered directly or indirectly to the site of neurological
damage or distress. Routes of administration of the cells of the
invention or compositions thereof include, but are not limited to,
. . . intranasal . . . routes of administration by delivery via
intracranial or intravertebral needles and/or catheters with or
without pump devices .
. . . Liquid or fluid pharmaceutical compositions, however, may
be administered to a more general location in the CNS or PNS
(e.g., throughout a diffusely affected area, such as would be the
case in Parkinson's disease or diffuse ischemic injury, for
example), inasmuch as neural progenitor cells have been shown
to be capable of extensive migration from a point of entry to the
nervous system to a particular location, e.g., by following radial
glia or by responding to chemical signals.
Messina i-fi-f 131-32 (underline added); see also Final Action 10 and Ans. 3,
10-11 (discussing Messina); cf App. Br. 3 (contending, "Messina does not
describe any method of delivering any cells to the brain of any mammal, let
alone the recited rat neural progenitor cells, let alone intranasally.").
DISCUSSION
We address both obviousness rejections together because Appellants
rely upon the same argument for each. After considering the evidence and
arguments, we conclude the weight of the evidence favors the Examiner's
conclusion of obviousness with regard to claims not directed to non-invasive
administration and that Appellants have not shown the Examiner's
determinations to be incorrect. However, where the appealed claims recite
limitations relating to non-invasive administration, we find the
5
Appeal2014-007425
Application 11/796,631
preponderance of the evidence supports Appellants' arguments for non-
obviousness.
The crux of Appellants' argument is that "Messina does not describe
any method of delivering any cells to the brain of any mammal, let alone the
recited rat neural progenitor cells, let alone intranasally" and, although
"Thome teaches intranasal delivery of insulin-like growth factor[,] ... there
is no rational basis by [which] one of skill in the art would have presumed
that methods of intranasal delivery small peptides like IGFl would similarly
deliver intact mammalian cells to the brain." App. Br. 3--4 and 7.
As determined by the Examiner, Messina's focus is the therapeutic
delivery of cells (stem cells and progenitor cells) to the brains of mammals
(such as rats, but more specifically humans) for treatment of, e.g., brain
trauma and Alzheimer's disease. FF1-FF4. While Messina is silent on
bypassing the blood brain barrier, we fail to see (and Appellants have not
explained) how the reference's treatments-of-focus would be possible
without such bypassing (whether by needles or catheters per FF4). 6 In any
event, Thome confirms that therapeutics can travel to the brain via intranasal
transport, as disclosed by Messina, and suggested intranasal transport as a
means for bypassing the blood brain barrier to achieve CNS delivery. As a
combination, these references would have rendered obvious the subject
6 We also note, Messina disclosed "administration by any acceptable route
known in the art to achieve delivery of live cells to the target neural tissues.
Typically, these include injection or infusion into the CNS or PNS, either in
a diffuse fashion or targeted to the site of neurological disease or distress."
Messina i-f 108. Although not relied upon in rejecting the claims and not
relied upon here, this supports that Messina taught delivery of live cells to
the brain, bypassing the blood brain barrier by injection or infusion.
6
Appeal2014-007425
Application 11/796,631
matter of claims 25-30, 32, 33, and 35-37 (none of which recite non-
invasive administration).
Appellants argue the declaration under 37 C.F.R. § 1.132 ofToufan
Parman (named inventor) provides evidence of nonobviousness. App. Br. 3
and 7; Reply Br. 2 and 3. The declarant' s testimony amounts to a
conclusion that, because intact mammalian cells would typically be at least
10 µm wide and it was only known that much smaller materials ( ~o. 5 µm)
could be delivered to the brain intranasally, intranasal delivery to the brain
of intact mammalian cells would not have been obvious. This is not
persuasive. Using the techniques of delivery disclosed by Messina, that is,
intranasal administration via surgical implantation or injection using needles
and/or catheters (FF4), the size of the cells delivered would be immaterial.
Regarding claims 31, 34, and 38--44, we read these claims to be
directed to "non-invasive" administration of the therapeutic. Claim 31
recites "the suspension is administered in nose drops to a naris of the rat,"
which we understand to mean that the suspension is merely dropped into the
rat's nostril, non-invasively. Claims 34 and 38 are similar in reciting "the
suspension is administered ... to each naris of the rat" and are interpreted
similarly. Independent claim 39 recites "administering intranasally and non-
invasively by nose drops to a naris of a rat" and is interpreted similarly.
Appellants contend such non-invasive techniques, e.g., delivery by nose
drops to a naris of a rat, would not have been obvious over the Messina-
Thome combination (or also including Ogawa and Noctor where
appropriate). App. Br. 5---6 and 8-9. We find the preponderance of the
evidence supports Appellants' contention.
7
Appeal2014-007425
Application 11/796,631
As briefly discussed above, Messina does not suggest a non-invasive
means of administering a therapeutic to the brain. See FF4. Messina
disclosed intranasal delivery of its therapeutic to the brain was accomplished
by needle and/or catheter, which would bypass the blood brain barrier, but
would not do so by drops in the naris, non-invasively. In view of the
Parman Declaration, discussed above, Thome is ambiguous as to whether it
would be possible for intact mammalian cells to traverse the blood brain
barrier via the intranasal route, as it is for smaller cells and molecules.
For the above reasons, we find that the evidence of record supports
the Examiner's determination on obviousness as to claims 25-30, 32, 33,
and 35-37, but does not as to claims 31, 34, and 38--44.
SUMMARY
The rejection of claims 25-34 and 39--42 under 35 U.S.C. § 103(a)
over ~v1essina and Thorne is affirmed as to claims 25-30, 32, and 33, but is
reversed as to claims 31, 34, and 39--42.
The rejection of claims 25--44 under 35 U.S.C. § 103(a) over Messina,
Thome, Ogawa, and Noctor is affirmed as to claims 25-30, 32, 33, and 35-
37, but is reversed as to claims 31, 34, and 38--44.
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).
AFFIRMED-IN-PART
8