Ex Parte Crine et al

Patent Trial and Appeal Board

Mar 22, 2018

12638527 (P.T.A.B. Mar. 22, 2018)

United States Patent and Trademark Office
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/638,527 12/15/2009 Philippe CRINE 50694-002005 5240
145747 7590 03/26/2018
r,lark4-F,lhina T T P/AleYinn Pharmaoentioals; Tno
EXAMINER
101 FEDERAL STREET
BOSTON, MA 02110
DESAI, ANAND U
ART UNIT PAPER NUMBER
1656
NOTIFICATION DATE DELIVERY MODE
03/26/2018 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.
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte PHILIPPE CRINE, GUY BOILEAU,
ISABELLE LEMIRE, and THOMAS P. LOISEL
Appeal 2016-005206
Application 12/638,5271
Technology Center 1600
Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
ULRIKH W. JENKS, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL
This Appeal under 35 U.S.C. § 134(a) involves claims 12—23, 37—41,
49, 51, 52, and 59—63 (App. Br. I).2 Examiner entered a rejection under 35
U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
1 Appellants identify the real party in interest as “Alexion Pharmaceuticals,
Inc.” (App. Br. 1.)
2 Pending “[cjlaims 24-31, 33-36, 42-48, 54, 56, 57, 64, and 65 [stand]
withdrawn” from consideration (App. Br. 1).
Appeal 2016-005206
Application 12/638,527
STATEMENT OF THE CASE
Appellants’ disclosure “relates to bone delivery compositions
comprising peptide motifs, engineered within the structure of a protein
through recombinant DNA technology to promote binding to bone matrix”
(Spec. 13). Claim 12 is representative and reproduced below:
12. A bone delivery conjugate comprising a structure selected
from the group consisting of:
A) X-Dn-Y-sALP-Z; and
B) Z-sALP-Y-Dn-X,
wherein X is absent or is an amino acid sequence of at
least one amino acid;
Y is absent or is an amino acid sequence of at least one
amino acid;
Z is absent or is an amino acid sequence of at least one
amino acid;
Dn is a poly aspartate wherein n = 10 to 16;
said sALP is a soluble tissue non-specific alkaline
phosphatase; and
said bone delivery conjugate is catalytically competent to
improve skeletal mineralization in bone.
(App. Br. 14.)
2
Appeal 2016-005206
Application 12/638,527
The claims stand rejected as follows:
Claims 12—23, 37-41, 49, 51, 52, and 59-63 stand rejected under 35
U.S.C. § 103(a) as unpatentable over the combination of Henthron,3 Shull,4 5 6
and Orgel.5,6
ISSUE
Did Examiner err by not considering Appellants’ rebuttal evidence?
FACTUAL FINDINGS (FF)
FF 1. Henthom discloses that “[hjypophosphatasia is an inborn error of
metabolism that is characterized clinically by defective bone mineralization
and biochemically by deficient activity of the tissue-non-specific isoenzyme
of alkaline phosphatase (TNSALP) in serum and in tissues” (Henthom 2501:
left column, first paragraph).
3 Paula S. Henthom and Michael P. Whyte Missense Mutations of the
Tissue-Nonspecific Alkaline Phosphatase Gene in Hypophosphatasia, 38
Clinical Chemistry 2501-2505 (1992).
4 Robert M. Shull et al., Enzyme replacement in a canine model of Hurler
syndrome, 91 Proc. Natl. Acad. Sci. USA 12937-12941 (1994).
5 Orgel et al., US 6,455,495 Bl, issued Sept. 24, 2002.
6 We recognize Examiner’s reference to the Milan and Whyte documents
{see generally Ans. 8). Examiner, however, did not include these documents
in the statement of the rejection {see Final Act. 5; see also Ans. 3). In this
regard, we note that “[wjhere a reference is relied on to support a rejection,
whether or not in a ‘minor capacity,’ there would appear to be no excuse for
not positively including the reference in the statement of the rejection.” In
re Hoch, 428 F.2d 1341, 1342 n.3 (CCPA 1970). In the event of further
prosecution, Examiner may consider whether to include the Milan and
Whyte documents in the statement of the rejection.
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Application 12/638,527
FF 2. Henthom discloses “Missense Mutations of the Tissue-Nonspecific
Alkaline Phosphatase Gene in Hypophosphatasia” (Henthom, Title; see
Final Act.7 5 (“Henthom . . . disclose[s] missense mutations of tissue-
nonspecific alkaline phosphatase in hypophosphatasia (also known as
soluble alkaline phosphatase) (see page 2501, 2nd paragraph, last sentence of
Introduction section)”); see Henthom 2501: left column, first paragraph
(Henthom “summarize[s] [prior] work leading to [the discovery of an
identical missense mutation in both alleles of the gene encoding TNSALP in
an inbred infant and] discuss[es] the . . . identification of additional missense
mutations in the TNSALP gene associated with the entire clinical spectmm
of hypophosphatasia”); see Ans. 3).
FF 3. Examiner finds that “Shull. . . disclose[s] the use of enzyme
replacement therapy for treatment of an enzyme deficient disease, Hurler
syndrome. The enzyme replacement therapy was effective in reducing the
clinical symptoms by infusion of a recombinant enzyme, a-L-iduronidase”
(Final Act. 5 (citing Shull, Abstract); see Shull, Abstract (“After weekly
administration of enzyme to three affected animals over a period of 3 mo,
the level of enzyme was about normal in liver and spleen, lower but
significant in kidney and lung, and barely detectable (0-5% of normal) in
brain, heart valves, myocardium, cartilage, and cornea”); see Ans. 3).
FF 4. Examiner finds that the combination of Henthom and Shull fails to
“disclose the conjugation of an enzyme with poly-aspartate from 10 to 16
residues long” and relies on Orgel to make up for this deficiency in the
combination of Henthom and Shull (Final Act. 5; Ans. 3).
7 Final Office Action (Final Act.) mailed October 3, 2014.
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Application 12/638,527
FF 5. Orgel discloses that “negatively charged peptide oligomers ... are
useful for delivering a wide variety of therapeutic agents to bone tissue,”
wherein:
Representative examples include antineoplastic agents such as
methotrexate; bone formation stimulating agents such as
insulin-like growth factors, bone morphogenic protein,
fibrobast growth factor, and platelet derived growth factor;
bone formation inhibiting agents such as glucocorticoids, and
vitamin D derivatives such as 1, 25-dihydroxyvitamin D3;
cathepsin K inhibitors, and agents which affect bone resorption
such as macrophage colony stimulating factor, interleukins and
other cytokines, bisphosphonate, calcitonin; and the like.
(Orgel 6: 40-51 ; see Final Act. 5 (Examiner finds that Orgel “disclose[s] a
composition for delivering a therapeutic agent to bone tissue,” which
comprises “a conjugate of a negatively charged peptide oligomer with a
therapeutic [protein] agent, and optionally, a pharmaceutically acceptable
carrier,” wherein “[t]he peptide oligomer is a glutamic acid decapetide”);
Ans. 3).
ANALYSIS
Examiner reasons that because Henthom discloses that mutated
TNSALP results in hypophosphatasia, which is “characterized clinically by
defective bone mineralization and biochemically by deficient activity of. . .
TNSALP in serum and in tissues,” Henthom provides a person of ordinary
skill in this art with “motivation to treat hypophosphatasia by administration
of a non-mutated tissue-nonspecific alkaline phosphatase” (Ans. 6; FF 1—2).
In this regard, Examiner finds that Shull provides evidence that
enzyme replacement therapies were known in the art at the time of
Appellants’ claimed invention (see Ans. 7; FF 3). Therefore, Examiner
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Application 12/638,527
reasons that, at the time of Appellants’ claimed invention, a person of
ordinary skill in this art would have selected a bone targeting poly-aspartate
oligomer, disclosed by Orgel, to target tissue non-specific alkaline
phosphatase to bone (see Ans. 7).
In sum, based on the combination of Henthron, Shull, and Orgel,
Examiner concludes that, at the time Appellants’ invention was made, it
would have been prima facie obvious “to conjugate the non-mutated soluble
purified alkaline phosphatase with the poly-aspartate oligomer to deliver the
pharmaceutical composition for hypophosphatasia therapy as disclosed by
the enzyme replacement therapy protocols disclosed in the art as evidenced
by Shull” (Final Act. 6—7; see also Ans. 5 and 6—7).
Notwithstanding the fact that Appellants’ claimed invention is
directed to a product or composition, there is no doubt on this record that the
reason, or motivation, underlying Examiner’s conclusion of obviousness is
premised on the use of a poly-aspartate oligomer — TNS ALP conjugate for
the treatment of hypophosphatasia (Final Act. 6—7; see Ans. 5—7). As
Examiner explains, a “person of ordinary skill in the art would have
constructed such a conjugate upon reading Henthom and Orgel” (Adv. Act.8
2). Thus, although Appellants’ claimed invention may not, as Examiner
asserts, require a “clinically meaningful therapeutic activity,” Examiner’s
obviousness rationale requires that a person of ordinary skill in this art have
a reasonable expectation of treating hypophosphatasia with a conjugate
within the scope of Appellants’ claimed invention. See Reply Br. 2. Absent
such a reasonable expectation of success Examiner’s conclusion of
obviousness fails, because, contrary to Examiner’s rationale, a person of
8 Advisory Action (Adv. Act.) mailed January 27, 2014.
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Appeal 2016-005206
Application 12/638,527
ordinary skill in this art would have had no expectation that such a conjugate
would work as Examiner asserts and, therefore, would not have found it
prima facie obvious to prepare such a conjugate. This is Appellants’
contention on this record.
Specifically, Appellants contend that “[n]o [mjotivation [ejxisted [f]or
[mjodifying [ajlkaline [pjhosphatase,” as suggested by Examiner (App. Br.
6 (emphasis omitted)); notwithstanding Examiner’s conclusion to the
contrary, “[n]o credible evidence existed when the application was filed that
persons having ordinary skill in the art would have had a reasonable
expectation of success in developing a modified alkaline phosphatase as a
therapeutically active bone delivery conjugate” (id. at 8); “[tjhere [w]as
[significant [ejvidence of [unexpected [rjesults” (id. at 9); and the claimed
invention satisfied a “[ljong [fjelt, [but] [u]nmet [n]eed” (id. at 11)
(emphasis omitted). In addition, Appellants direct attention to the Crine
Declaration9 to support their contentions (see generally App. Br. 7 and 10).
As Appellants explain, “Examiner has erred by disregarding the
Declaration of Dr. Philippe Crine” (Reply Br. 1). We agree. See In re Soni,
54 F.3d 746, 750 (Fed. Cir. 1995) (“all evidence of nonobviousness must be
considered when assessing patentability”); see also In re Sullivan, 498 F.3d
1345, 1350-53 (Fed. Cir. 2007). Here, as in Sullivan, “[t]he issue [] is not
whether a claim recites a new use, but whether the subject matter of the
claim possesses an unexpected use. That unexpected property is relevant,
9 Declaration of Dr. Philippe Crine, signed January 13, 2014. Examiner
entered this Declaration into the record on January 14, 2014 (see Adv. Act.
1; Reply Br. 1).
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Application 12/638,527
and thus the declaration^ describing it should have been considered.
Sullivan, 498 F.3d at 1353.
CONCLUSION OF LAW
The Examiner erred by not considering Appellants’ rebuttal evidence.
The rejection of claims 12—23, 37-41, 49, 51, 52, and 59-63 under 35
U.S.C. § 103(a) as unpatentable over the combination of Henthron, Shull,
and Orgel is reversed.
REVERSED
8