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 .
Claimed Priority
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Claims 1-8 are currently pending and are the subject of this Office Action.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5-7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 5-7 recite intended uses of the pharmaceutical composition in the preamble. Claims 5-7 are thus identical to claim 4. An intended use will not limit the scope of the claim because it merely defines a context in which the invention operates. (Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 320 F.3d 1339, 1345 (Fed. Cir. 2003)). Additionally, a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. (See MPEP 707.07(f) and 2141.02 I; In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and MPEP 2111.02 II; Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951)). In the instant case, the intended use does not create a structural difference and the body of the claim does not depend on the intended use for completeness but rather can stand alone. Consequently, the intended use is not limiting. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (WO 2020/024825), as evidenced by Luo et al. (Biochemical Pharmacology 183 (2021) 114318- published online November 5, 2020) in view of Choe et al. (Bull. Korean Chem. Soc. 2017, p 1-5; DOI: 10.1002/bkcs.11287).
Yang
Yang teaches compounds of formula
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as inhibitors of FAK, ALK and ROS1, for the treatment of cancers, preferably cancers carrying an EGFR mutation or that are EGFR inhibition-resistant (see at least abstract, p. 11-12, 23, 26). Pharmaceutical compositions with acceptable carriers and further containing an anticancer drug can be found throughout the reference, particularly in the tests and claims. Particularly, compound 5
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(APG-2449) of the prior art is a multi-kinase inhibitor which enhances the antitumor activity in drug combinations via EGFR/FAK pathway inhibition. See test results in prior art Yang; see additionally the evidentiary reference Luo et al.
Choe
Choe teaches compounds which are similar substituted 2,4-dianilinopyrimidines as those of Yang, and are also ALK and EGFR inhibitors for anticancer treatment. See Figure 2 for Brigatinib and how it was derivatized into a compound of formula
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. Choe showed that while the compound in which R1 is
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is a potent inhibitor of mutant EGFR, more potent inhibitors can be obtained when R1 is
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. See Table 1 for compound TRE-069. There was a difference by a factor of about 8.7 in the improvement.
The table shows various trends in the modifications.
Ascertainment of the Difference Between the Prior Art and the Claims
(MPEP §2141.012)
The difference between the compounds of Yang et al. and the claimed compounds is a sulfone group
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instead of a sulfonamide group
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, or
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.
Finding of prima facie obviousness--rational and motivation (MPEP §2142-2413)
One of ordinary skill in the art is a chemist practitioner with the knowledge and skills of the authors of the cited references. Someone preparing these compounds would be trained in organic chemistry and would recognize the very close structural similarity and would expect these compounds to have the same properties. One of ordinary skill would have been motivated to replace the sulfone group
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in the compounds of formula I
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, particularly, in the preferred compound 5
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(APG-2449) of Yang et al., with a sulfonamide group
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exemplified in the compounds of Choe above, because Choe taught that more potent inhibitors of mutant EGFR for the treatment of cancers can be obtained when doing so.
Particularly, the claimed compound of formula
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(Example 2) is prima facie obvious. An improvement of a factor of about 8.7 would have been reasonably expected.
The claimed compounds have exactly similar formula and the same use as the compounds of Yang; they are analogs possessing chemical and pharmacological similarities. There would have been a high expectation of success due to that the prior at teaches how to prepare and use the compounds which share the same groups.
Under the Supreme Court rationales in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007), here at least exemplary rationales (A), (B) and (G) apply:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Claims 4-8 recite a composition “for the treatment of cancer or hyperproliferative disease”, and recite particular cancers, and that they are caused by ALK overexpression, mutation or EGFR mutation. However, the composition is the same no matter what its intended use is. Nothing precludes the use of the composition as instantly recited. According to MPEP 2111.02, Section II, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) (“where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”). In the instant case, the body of the claims intrinsically set forth all of the limitations of the composition of the claims.
Secondary considerations:
The instant specification provides comparative tests between the sulfone containing compound of Yang and Luo, APG-2449, and claimed sulfonamide containing compounds. See Tables 1 and 2 of the instant specification. Applicant’s example 2 can be compared to the known compound APG-2449, since the only difference is that of the sulfone group instead of the sulfonamide group
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. However, the results obtained by applicant do not appear unexpected and significant in view of the prior art teachings discussed above. An improvement in activity of a factor of about 8.7 would have reasonably been expected. The other examples, compounds 1 and 3-8, additionally differ in other areas that are not the replacement of a sulfone group with sulfonamide group
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,
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, or
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.
Claim(s) 1-2 and 4-8 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (US 2020/0179384), as evidenced by Choe et al. as above (Bull. Korean Chem. Soc. 2017, p 1-5; DOI: 10.1002/bkcs.11287), in view of Kang et al. (Cancer Letters 374 (2016) 272-278) and also evidenced by Yang et al. (WO 2020/024825) as above.
Lee
Lee teaches compounds of formula (I)
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, as having high inhibitory effect on FLT3 and on mutated EGFR, that can be used for the treatment of cancer with EGFR mutation or FLT3, and that show synergy when combined with other anticancer drugs. See page 3 and tests. Compound example 1
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is the same very active compound TRE-069 of Choe. Example 3
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is the same very active compound #15 of Choe. Example 4
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is the same very active compound #14 of Choe.
Pharmaceutical compositions with acceptable excipients and further containing an anticancer drug (cetuximab) can be found throughout the reference, particularly at para [0155] and in the tests.
Choe
Choe teaches compounds which are the same as in Lee, and other similar substituted 2,4-dianilinopyrimidines, which are ALK and EGFR inhibitors for anticancer treatment. See Figure 2 for Brigatinib compared to compounds formula
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, and particularly to compound TRE-069, 14 and 15.
Kang
Kang disclosed that “minor modifications to ceritinib enhance anti-tumor activity in EML4-ALK positive cancer”. Ceritinib
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is an inhibitor of FAK, ALK and mutant EGFR (T790M, L858R). See Table 4. The small modifications to the ceritinib structure were the addition of a double bond on the piperidine ring
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, and for KRCA-386, also the removal of a CH3 group. The small modifications afforded KRCA-386, which has superior efficacy over ceritinib in vitro and in vivo, nearly no cytotoxic effect on the cells, better inhibitory activity against ALK mutants, and shows higher penetration through the BBB than ceritinib. See at least page 278 and Table 4.
Ascertainment of the Difference Between the Prior Art and the Claims
(MPEP §2141.012)
The difference between the compounds of Lee et al. in which
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and the claimed compounds is the lack of a double bond at position 3-4 of the piperidine ring (as in 1,2,3,6-tetrahydropyridine).
Finding of prima facie obviousness--rational and motivation (MPEP §2142-2413)
One of ordinary skill in the art is a chemist practitioner with the knowledge and skills of the authors of the cited references. Someone preparing these compounds would be trained in organic chemistry and would recognize the very close structural similarity and would expect these compounds to have the same properties. One of ordinary skill would have been motivated to make the small modification of adding a double bond at position 3-4 in the piperidine ring of the compounds of Lee or Choe above because Kang taught that this could provide superior efficacy, possibly less toxicity, and more potent inhibitors against FAK, ALK mutants and EGFR mutants (T790M, L858R) for the treatment of cancers.
There would have been a high expectation of success due to that the prior at teaches how to prepare and use the compounds which share the same groups.
In addition, Yang is evidence that this small modification has been practiced in similar compounds that have the same use as the compounds of Lee and Choe. Formula (I) of Yang:
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.
Under the Supreme Court rationales in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007), here at least exemplary rationales (A), (B) and (G) apply:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Claims 4-8 recite a composition “for the treatment of cancer or hyperproliferative disease”, and recite particular cancers, and that they are caused by ALK overexpression, mutation or EGFR mutation. However, the composition is the same no matter what its intended use is. Nothing precludes the use of the composition as instantly recited. According to MPEP 2111.02, Section II, if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) (“where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”). In the instant case, the body of the claims intrinsically set forth all of the limitations of the composition of the claims.
Conclusion
Claims 1-8 are rejected. No claim is in condition for allowance.
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/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621
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