Ex Parte Luten

Patent Trial and Appeal Board

Sep 20, 2016

12645794 (P.T.A.B. Sep. 20, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/645,794
38427 7590
Mark R Buscher
7371 Atlas Walk Way
#136
12/23/2009
09/22/2016
Gainesville, VA 20155
FIRST NAMED INVENTOR
Jordy Luten
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.
SYN-0125 8943
EXAMINER
GAR YU, LIANKO G
ART UNIT PAPER NUMBER
1676
NOTIFICATION DATE DELIVERY MODE
09/22/2016 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):
PTO.Mail@buscherlaw.com
buscher@synthonip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JORDY LUTEN 1
Appeal2014-003423
Application 12/645,794
Technology Center 1600
Before DONALD E. ADAMS, TA WEN CHANG, 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 process
of making purified copolymer- I by ultrafiltration, which have been rejected
as obvious. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm-in-part.
STATEMENT OF THE CASE
"'Copolymer peptides' are generally formed by a random
copolymerization of amino acids" forming complex reaction mixtures.
(Spec. i-f 4.) Purification steps to remove undesired products after
polymerization are known. (Spec. i-fi-16-9.) According to Appellant, "[t]here
1 Appellant identifies the Real Party in Interest as Synthon BV. (Appeal Br.
1.)
Appeal2014-003423
Application I2/645,794
remains a need, however, for an easier and/or more industrially applicable
ultrafiltration method for purifying complex reaction mixtures." (Spec. i-f
IO.)
Claims 6-8, I3-I5, I9, 20, 24, and 25 are on appeal. Claims 6 and I9
are representative and read as follows:
6. A process of making purified Copolymer-I (COP-I), which
compnses:
(i) adding an aqueous acid solution to a reaction mixture
containing unprotected COP- I polypeptides to obtain COP- I
acid addition salts in a modified reaction mixture; and
(ii) ultrafiltering said modified reaction mixture
containing said COP-I acid addition salts to form purified
COP-I acid addition salts;
wherein said adding step (i) is performed before subjecting said
reaction mixture containing the unprotected COP- I
polypeptides to any ultrafiltration; and wherein said
ultrafiltering step (ii) is carried out with the addition of an
aqueous acid feeding solution to said modified reaction
mixture.
(Appeal Br. 20.)
I9. In a process for purifying Copolymer-I (COP-I)
polypeptides which comprises subjecting unprotected COP- I
polypeptides in a reaction mixture to ultrafiltration wherein the
COP-I polypeptides become purified in the retentate solution
and the pH of the retentate decreases during the ultrafiltration,
the improvement for which comprises adding an aqueous acid
feeding solution to the reaction mixture or retentate at least
during the ultrafiltration process and not later than the retentate
achieves a pH of I 0.
(Appeal Br. 22.)2
2 Claims 9-I 0 and I 8 are also pending, but have been withdrawn from
consideration. (Appeal Br. 2I-22.)
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Application 12/645,794
The following ground of rejection by the Examiner is before us on
review:
Claims 6---8, 13-15, 19, 20, 24, and 25 under 35 U.S.C. § 103(a) as
unpatentable over Ray3 and Millipore. 4
DISCUSSION
Claim 6
The Examiner finds that Ray teaches a method of preparing the
copolymer glatiramer ("Copolymer- I") that includes adding acetic acid to
deprotected glatiramer to achieve a pH of about 7 to about 8 "followed by
removing undesired low molecular weight glatiramer fragments by dialysis
or diafiltration" where the diafiltration can be Tangential Flow Filtration
("TFF"). (Ans. 2-3; Final Action 11.) The Examiner finds Millipore
teaches that TFF diafiltration "utilizes a feed tank and a feeding stream in
which the diafiltration buffer and recycled retentate are fed to the filtration
module (filter)." (Ans. 3.)
The Examiner notes that Ray teaches "[i]n a preferred embodiment
[that] the deprotected glatiramer is subjected to dialysis in water followed by
dialysis in aqueous acetic acid solution." (Ans. 3.) The Examiner,
recognizing that Ray does not disclose the claimed "ultrafiltration ... with
the addition of an aqueous acid feed solution," finds that "[i]t would have
been obvious to one of ordinary skill in the art to substitute diafiltration for
3 Ray et al. US 2006/0154862 Al, published Jul. 13, 2006.
4 EMD Millipore, A Hands-On Guide to Ultrafiltration/Diafiltration
Optimization using Pellicon Cassettes, 1-12, May 2008, ("Millipore").
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Application I2/645,794
dialysis because dialysis and diafiltration have been recognized both in the
art and specifically by Ray ... as functionally equivalent methods." (Ans.
3.) The Examiner further finds that one of ordinary skill in the art "would
have a reasonable expectation of success because Ray ... explicitly teach
the use of diafiltration and in particular Tangential Flow Filtration
diafiltration as an alternative to dialysis." (Ans. 3.)
We disagree with the Examiner's conclusion of obviousness of claim
6.
"In rejecting claims under 35 U.S.C. § I03, 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 I53I, I532 (Fed.
Cir. I993). Claim 6 requires "said ultrafiltering step (ii) is carried out with
the addition of an aqueous acid feeding solution to said modified reaction
mixture." (Appeal Br. 20 (emphasis added).) According to claim 6, the
modified reaction mixture is that which is formed after "adding an aqueous
acid solution to a reaction mixture containing unprotected COP-I
polypeptides to obtain COP-I acid addition salts." (Id.) We agree that Ray
makes the claimed modified reaction mixture when adding acetic acid to
deprotected glatiramer, thereby achieving a reaction mixture having a pH of
between 7 and 8. (Ray i-fi-155-57.) And it is true that Ray also teaches a
separate step of dialysis of a reaction mixture that includes the deprotected
glatiramer with aqueous acetic acid. (See, e.g., Ray i-fi-158, 79, I03.)
However, as the Examiner notes (Ans. 3), the Ray dialysis process in which
aqueous acetic acid is used "follow[s]" dialysis of Ray's "modified reaction
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Appeal2014-003423
Application 12/645,794
mixture" with water. (Id.) As such, the mixture that is dialyzed with
aqueous acetic acid is necessarily not the claimed "modified reaction
mixture"; it is instead a modified "modified reaction mixture." The
Examiner does not rely on additional references to remedy this deficiency.
In light of the foregoing, we conclude that the Examiner has not shown by a
preponderance of the evidence of record that Ray and Millipore would have
made obvious the claimed method of making purified Copolymer- I in which
the "ultrafiltering step (ii) is carried out with the addition of an aqueous acid
feeding solution to said modified reaction mixture." We therefore reverse
the Examiner's rejection of claim 6.
Claims 7, 8, 13-15, 24, and 25 depend either directly or ultimately
from claim 6. The Examiner's rejection of these additional claims does not
address the deficiency noted above. Thus, the Examiner has also failed to
satisfy the initial burden of presenting evidence to establish a prima facie
case ofunpatentability of claims 7, 8, 13-15, 24, and 25.
Claim 19
The Examiner finds that Ray teaches "subjecting deprotected
glatiramer dissolved in an aqueous acetic acid solution (aqueous acid
feeding solution) to diafiltration." (Final Action 12; Ans. 6.) In particular,
the Examiner notes that prior to dialysis or diafiltration, Ray teaches the
addition of aqueous acetic acid achieving a pH of 7 or 8, which meets the
active step of "adding an aqueous acid feeding solution to the reaction
mixture or retentate at least during the ultrafiltration process and not later
than the retentate achieves a pH of 10." (Ans. 6, 12.)
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Application I2/645,794
We agree with the Examiner's finding that Ray teaches that
deprotected glatiramer is subjected to diafiltration and that acetic acid is
added to the reaction mixture. In particular, Ray teaches two acetic acid
additions: one addition is to the deprotected glatiramer to adjust the pH to
about 7 or 8 (Ray i-f 57) and a second addition is in the process of removing
"[ u ]ndesired low molecular weight polypeptide or glatiramer fragments, i.e.,
less than about 2 kDa, and high molecular weight polypeptide or glatiramer
fragments, i.e., greater than about 40 kDa" (Ray i-f 58).
Appellant's argument that claim I 9 requires that "an aqueous acid
feeding solution [be] added at least during ultrafiltration and not later than
the retentate achieves a pH of IO" and that Ray does not teach a "feeding
solution is used ... during filtration" (Appeal Br. I6) is unavailing. That is
because claim I 9 requires either "adding an aqueous acid feeding solution to
the reaction mixture or retentate at least during the ultrafiltration
process ... " in a process for purifying COP-I where unprotected COP-I is
subjected to ultrafiltration. (Claim I9 (emphasis).) The grammatical
structure of this claim does not require that the addition of aqueous acid
feeding solution to the reaction mixture occur "during filtration" or "not later
than the retentate achieves a pH of IO." Under the broadest reasonable
interpretation consistent with the specification, the limitation can be met by
simply adding the aqueous acid feeding solution to the reaction mixture.
We note that Appellant's specification teaches that acid can be
combined with the reaction mixture "before the start of ultrafiltration" or
"while the reaction mixture is undergoing ultrafiltration." (Spec. i-fi-12I, 37.)
Furthermore, we do not find the specification defines "aqueous acid feeding
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Application 12/645,794
solution" in a manner requiring addition of an aqueous acid during filtration.
Indeed, there is no specific definition for "feeding solution" in the
specification; rather, the specification simply indicates that a feeding
solution, "when supplied" "is normally an aqueous solution of the same acid
as used for adjusting the pH" and "is used as the aqueous acid solution in the
combining or adding step" (Spec. i-f 28 (emphasis added)) and that it can be
"combined with the reaction mixture ... at the start of the ultrafiltration, or,
during the ultrafiltration" (Spec. i-f 37). As noted above, Ray teaches adding
acetic acid solution two times to a reaction mixture of unprotected COP- I
that is ultimately subjected to ultrafiltration. Thus, because Ray teaches
adding aqueous acetic acid to the reaction mixture, which mixture is
subjected to ultrafiltration, Ray meets the limitation that an aqueous acid
feeding solution be added "to the reaction mixture or retentate at least during
the ultrafiltration process and not later than the retentate achieves a pH of
1 O."
For the reasons discussed above, Appellant's argument that Ray does
not "teach or suggest ultrafiltration with an aqueous acid feeding solution"
(Appeal Br. 16) is also unavailing.
In addition, we note that the fact that Ray's examples in which
ultrafiltration by Tangential Flow Filtration (TFF) is employed do not
describe dual filtration, i.e., once with water and once with acetic acid, is not
dispositive. As the Examiner noted (Ans. 9), Ray teaches that removal of
undesired low molecular weight and high molecular weight polypeptides can
be by dialysis or diafiltration and that the separation can involve two steps,
one in which water is employed, and the second in which aqueous acetic
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Application 12/645,794
acid is employed. (Ray i-f 58.) A reference is available for all that it teaches
to a person of ordinary skill in the art. In re Inland Steel Co., 265 F.3d 1354,
1356 (Fed. Cir. 2001); see also Merck & Co. Inc. v. Biocraft Labs., Inc., 874
F.2d 804, 807 (Fed. Cir. 1989). And "in a section 103 inquiry, 'the fact that
a specific [embodiment] is taught to be preferred is not controlling, since all
disclosures of the prior art, including unpreferred embodiments, must be
considered."' Merck & Co. Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807
(Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750 (CCPA 1976))
(holding that the prior art's disclosure of a multitude of combinations failed
to render any particular formulation less obvious). We agree with the
Examiner (Ans. 10-11) that one of ordinary skill in the art would have found
it obvious to substitute diafiltration, such as by TFF, taught by Ray for the
two dialysis steps noted to be "preferred" with a reasonable expectation of
success. Ray itself indicates that dialysis and diafiltration are
interchangeable with respect to the separation of undesired low and high
molecular weight polypeptides. (Ray i-f 58.)
We also do not find persuasive Appellant's argument that the
Examiner ignored "functional limitation[ s ]" recited in the "wherein" clause
of claim 19 (Appeal Br. 16-17). Because the body of claim 19 recites an
improvement to the process recited in the preamble, claim 19 is
a Jepson format claim. See Sjolund v. Musland, 847 F.2d 1573 (Fed. Cir.
1988). "[T]he preamble of a Jepson claim is impliedly admitted to be prior
art." Id. at 1577. For the reasons discussed above, the active step of the
claim that is an alleged "improvement" over the prior art, is rendered
obvious by Ray and Millipore.
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Application 12/645,794
Finally, we do not find persuasive Appellant's argument that "the
unexpectedly superior results establish unobviousness" (Appeal Br. 18).
According to Appellant, "precipitation is seen to start as the pH drops [from
10 or above] to around 8-9" and that "[ s ]tarting the aqueous acid feeding
solution at the claimed higher pH of at least 10 would thus be early enough
to avoid precipitation and/or clogging." (Appeal Br. 18.) In the first place,
the claims do not require a starting pH at the time of ultrafiltration be above
1 O; and, for the reasons discussed above, one embodiment encompassed by
claim 19 is that the purification process that results in a decreasing pH of the
retentate during ultrafiltration includes that acetic acid be added to the
reaction mixture that is subject to ultrafiltration. In light of the fact that
claim 19 is a Jepson claim, the decreasing pH of the retentate is a feature of
the prior art, and Ray teaches or suggests an ultrafiltration process in which
acetic acid is added to the reaction mixture. Appellant does not provide
evidence of unexpected results of such a process. Rather, Appellant simply
shows in Example 2 that addition of acetic acid after ultrafiltration without
acetic acid clears alleged clogging of the filter. As the Examiner noted (Ans.
10-11 ), such would be expected in the modified TFF diafiltration process of
Ray in which acetic acid was added to the reaction mixture lowering the pH
of the reaction mixture to about 7 or 8 and diafiltering by TFF with acetic
acid after diafiltering by TFF with water (Ray i-f 58). "To be particularly
probative, evidence of unexpected results must establish that there is a
difference between the results obtained and those of the closest prior art, and
that the difference would not have been expected by one of ordinary skill in
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the art at the time of the invention." Bristol-Myers Squibb Co. v. Teva
Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014).
Claim 20 has not been argued separately and therefore falls with claim
19. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We reverse the rejection of claims 6-8, 13-15, 24, and 25 under 35
U.S.C. § 103(a) as unpatentable over Ray and Millipore.
We affirm the rejection of claims 19 and 20 under 35 U.S.C. § 103(a)
as unpatentable over Ray and Millipore.
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
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