DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-7, 9-20, 22-24 and 26-28 are pending in this application.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL. —The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 26 and 27 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first, paragraph, because the specification, while being enabling for anaplastic large cell lymphoma, inflammatory myofibroblastic tumor, breast cancer, colorectal cancer, esophageal squamous cell cancer, large B-cell lymphoma, renal cell cancer or non-small cell lung cancer, does not reasonably provide enablement for disease or disorder characterized or mediated by aberrant ALK activity and the method of treating cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The nature of the instant invention has claims, which bifunctional compounds where the ALK Targeting Ligand of (TL-1), (TL-2) or (TL-3) are bound through a linker to a Degron
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HOW TO USE: Claims 26 and 27 are drawn to a method of treating a disease or disorder characterized or mediated by aberrant ALK activity and the method of treating cancer. Any evidence presented must be commensurate in scope with the claims and must clearly demonstrate the effectiveness of the claimed compounds. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The scope of claim 26 includes diseases and/or disorders not even known at this time, which may be associated with aberrant ALK activity. While the treatment of anaplastic large cell lymphoma, inflammatory myofibroblastic tumor, breast cancer, colorectal cancer, esophageal squamous cell cancer, large B-cell lymphoma, renal cell cancer and non-small cell lung cancer have been linked with aberrant ALK activity the art does not recognize use of such broad-based drugs for treating all
disorders instantly embraced.
The treatment of cancer or diseases or disorders associated with aberrant ALK activity generally cannot possibly be considered enabled.
As a general rule, enablement must be commensurate with the scope of claim language.
MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must
teach those skilled in the art how to make and use the full scope of the claimed invention
without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513
(Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without
undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva
Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78
USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a
legitimate rejection.” The principle was explicitly affirmed most recently in Liebel-Flarsheim Co.
v. Medrad, Inc. 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc.,
501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503
F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d
993, 85 USPQ2d 1826 (Fed. Cir. 2008).
By way of background, four cases are of particular relevance to the question of
enablement of a method of treating solid tumors broadly or even generally:
In In re Buting, 57 CCPA 777, 418 F.2d 540, 163 USPQ 689, the claim was drawn to
“The method of treating a malignant condition selected from the group consisting of leukemias, sarcomas, adenocarcinomas, lymphosarcomas, melanomas, myelomas, and ascitic tumors”
using a small genus of compounds. The Court decided that human testing “limited to one
compound and two types of cancer” was not “commensurate with the broad scope of utility
asserted and claimed”.
In Ex parte Jovanovics, 211 USPQ 907 the claims were drawn to “the treatment of
certain specified cancers in humans” by the use of a genus of exactly two compounds, the
Nformyl or N-desmethyl derivative of leurosine. Applicants submitted “affidavits, publications
and data” for one of the compounds, and a dependent claim drawn to the use of that species
was allowed. For the other, no data was presented, applicants said only that the other
derivative would be expected to be less effective; claims to the genus were refused.
In Ex parte Busse, et al., 1 USPQ2d 1908, claims were drawn to “A therapeutic method
for reducing metastasis and neoplastic growth in a mammal” using a single species. The
decision notes that such utility “is no longer considered to be “incredible”, but that “the utility in
question is sufficiently unusual to justify the examiner's requirement for substantiating evidence.
Note also that there is also a dependent claim 5 which specified “wherein metastasis and
neoplastic growth is adenocarcinoma, squamous cell carcinoma, melanoma, cell small lung or
glioma.” The decision notes that “even within the specific group recited in claim 5 some of the
individual terms used actually encompass a relatively broad class of specific types of cancer,
which specific types are known to respond quite differently to various modes of therapy.”
In Ex parte Stevens, 16 USPQ2d 1379 a claim to “A method for therapeutic or
prophylactic treatment of cancer in mammalian hosts” was refused because there was “no
actual evidence of the effectiveness of the claimed composition and process in achieving that
utility.”
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988),
one considers the following factors to determine whether undue experimentation is required: (A)
The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction
provided by the inventor; (G) The existence of working examples; and (H) The quantity of
experimentation needed to make or use the invention based on the content of the disclosure.
Some experimentation is not fatal; the issue is whether the amount of experimentation is
“undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
Solid tumor is not a single disease, or cluster of closely related disorders. There are
hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers
are highly heterogeneous at both the molecular and clinical level, something seen especially in,
for example, the cancers of the breast, brain and salivary glands. They can occur in pretty
much every part of the body. Here are some assorted categories:
It is important to note that tumors can need to be treated quite differently even though
they are tumors of the same organ. For example, the drugs used most often to treat Wilms
tumor, the most common malignant tumor of the kidneys in children, are actinomycin D and
vincristine. Such drugs are never used with clear cell renal carcinoma, which is treated,
although without much success, with immunotherapy using the cytokines interleukin-2 and
interferon-alpha. However, such immunotherapy has never been established as effective in
non-clear cell RCC forms such as papillary renal cell carcinoma. Despite strenuous efforts over
a period of decades, no chemotherapeutic agent has ever been found effective against this
cancer. Cancers of the stomach can be lymphomas, GISTs, carcinoid tumors, carcinomas, or
soft tissue sarcomas, and for a single agent to be effective against all or even most of these
categories would be contrary to what is known in oncology.
(7) The quantity of experimentation needed: Given the fact that, historically, the development of
new cancers drugs have been difficult and time consuming, and especially in view of factors 1
and 4 and 6, the quantity of experimentation needed is expected to be great.
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the
evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
In view of the lack of direction provided in the specification regarding starting materials, the lack of working examples, and the general unpredictability of chemical reaction, it would take an undue amount of experimentation for one skilled in the art to make the claimed compounds and therefore practice the invention. To be enabling, the specification of a patent must teach those skilled in the art how to make and use the scope of the claimed invention without undue experimentation. The applicants are not entitled to preempt the efforts of others. The test for determining compliance with 35 U.S.C. § 112, is whether the applicants have clearly
defined their invention.
Where the utility is unusual or difficult to treat or speculative, the examiner has authority
to require evidence that tests relied upon are reasonably predictive of in vivo efficacy by those
skilled in the art. See In re Ruskin, 148 USPQ 221; Ex parte Jovanovics, 211 USPQ 907; MPEP 2164.05(a).
Patent Protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. Tossing out the mere germ of an idea does not constitute enabling disclosure. Genentech Inc. v. Novo Nordisk 42 USPQ2d 1001.
As stated in the MPEP, 2164.08 ''[t]he Federal Circuit has repeatedly held that the
specification must teach those skilled in the art how to make and use the full scope of the
claimed invention without undue experimentation. ln re Wright, 999 F.2d 1557, 1561 27
USPQ2d 1510, 1513 (Fed. Cir. 1993). Nevertheless, not everything necessary to practice the
invention need be disclosed. In fact, what is well known is best omitted. In re Buchner, 929 F.2d
660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991). AII that is necessary is that one skilled in
the art be able to practice the claimed invention, given the Ievel of knowledge and skill in the art. Further the scope of enablement must only bear a reasonable correlation to the scope of the
claims. See, e.g., In re Fisher, 427 F.2d 833, 839,166 USPQ 18, 24 (CCPA 1970). As concerns the breadth of a claim relevant to enablement, the only relevant concern should be whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate with the scope of protection sought by the claims. In re Moore, 439 F.2d 1232, 1236, 169 USPQ 236, 239 (CCPA 1971). See also Plant Genetic Sys., N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003) (alleged pioneer status of invention irrelevant to enablement determination.''
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 19, 20 and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The following reasons apply:
Claims 19 and 20 recite the limitation "a bond" in the definition of linker. There is insufficient antecedent basis for this limitation in the claim.
Claim 22 recites the limitation "a bond" in the compound (15) with respect to the definition of linker. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-7, 9-14, 18-20, 22-24 and 26-28 is/are rejected under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Zhao et al., U.S. Patent Application Publication No. 2022/0306659. Zhao teaches the bifunctional compound of formula (I) where the ALK Targeting Ligand is (TL-1) wherein R1 is -P(O)(Me)2; R3 is Cl; p is 1; R2 is methoxy; A1 is a ring where X1 is N and X2 is CH; the Linker is - W1 - Z1 - (CH2)p1 - (W - CH2 - CH2)p2 - (CH2)p3 - Z2 - W2 - wherein W1 is absent; Z1 is 1,4-piperzinylene; -(CH2)p1 - (W - CH2 - CH2)p2 -(CH2)p3- Z2 is in the various combination of p1, p2, p3, W and Z2 is -CH2CH2CH2CH2CH2CH2CH2-; and W2 is O; Degron wherein Z is C=O; Y1 is N; Y2 is CH; m is 1; n is 1; as set forth in the example in the first line on page 59, C150 on page 140, and line 2 and page 273. The generic structure of Zhao encompasses the instantly claimed compounds, compositions and method of use of the bifunctional compounds of formula (I) (see Formula I-G, page 12) as claimed herein. Example C150 differs only in the nature of the ring A, -L-, R1, R2, R3, T, Z, L2, E, m, L-1, s1, Rs1 and Y substituents of the bifunctional compounds of formula (I-G). Paragraph [0182]-[0204]. The compounds of the instant invention are generically embraced by Zhao in view of the interchange ability of A, -L-, R1, R2, R3, T, Z, L2, E, m, L-1, s1, Rs1 and Y substituents of the bifunctional ring system. Thus, one of ordinary skill in the art at the time the invention was made would have been motivated to select for example piperidinylene for the E substituent of the reference as well as other possibilities from the generically disclosed alternatives of the reference and in so doing obtain the instant compounds in view of the equivalency teachings outlined above.
Claim(s) 1, 3, 4, 7, 10, 12, 16-20, 23, 24 and 26-28 is/are rejected under 35 U.S.C. 102(a)(2) as anticipated by Xu et al., CN 112341436. Xu teaches the bifunctional compound of formula (I) where the ALK Targeting Ligand is (TL-3) wherein R4 is CN; R5 is CH2CH3; R6 is H; X3 is CMe2; and A2 is absent; the Linker is - W1 - Z1 - (CH2)p1 - (W - CH2 - CH2)p2 - (CH2)p3 - Z2 - W2 - wherein W1 is absent; Z1 is piperidinylene; p1 is 0; p2 is 0; p3 is 0; Z2 is absent and W2 is absent; Degron wherein Z is C=O; Y1 is N; Y2 is N; m is 2; n is 2; as set forth in the example in paragraph [0024], first species in line 1 on page 6/32.
Claim(s) 1-4, 7, 10, 12, 13-20, 23, 24 and 26-28 is/are rejected under 35 U.S.C. 102(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Xie et al., Journal of Medicinal Chemistry. Xie teaches the bifunctional compound of formula (I) where the ALK Targeting Ligand is (TL-3) wherein R4 is CN; R5 is CH2CH3; R6 is H; X3 is CMe2; and A2 is absent; the Linker is - W1 - Z1 - (CH2)p1 - (W - CH2 - CH2)p2 - (CH2)p3 - Z2 - W2 - wherein W1 is absent; Z1 is piperidinylene or absent; p1 is 0; p2 is 0; p3 is 0; Z2 is absent and W2 is absent; Degron wherein Z is C=O; Y1 is N; Y2 is N; m is 2; n is 2; as set forth in the example 13 and 21. The generic structure of Xie encompasses the instantly claimed compounds, compositions and method of use of the bifunctional compounds of formula (I) as claimed herein. Examples 13 and 21 differs only in the nature of the ALK small molecule inhibitor of the bifunctional compounds of formula (I). Figure 1 sets forth several ALK small molecule inhibitors such as Crizotinib, Ceritinib, etc. The compounds of the instant invention are generically embraced by Xie in view of the interchange ability of ALK small molecule inhibitor of the bifunctional ring system. Thus, one of ordinary skill in the art at the time the invention was made would have been motivated to select for example ALK Targeting Ligand of Formula TL-20 for the ALK small molecule inhibitor substituent of the reference as well as other possibilities from the generically disclosed alternatives of the reference and in so doing obtain the instant compounds in view of the equivalency teachings outlined above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRENDA L COLEMAN whose telephone number is (571)272-0665. The examiner can normally be reached Mon-Fri 10-6 (flex).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey H. Murray can be reached on 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624