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 .
Election/Restrictions
Claims 19-32 are pending. Claims 11-18 were canceled, claim 19 was amended, and claims 20-32 were added in the Reply filed 6/25/2026. Claims 20-22 and 25-32 are withdrawn by original presentation. Claims 19 and 23-24 are presently considered.
Election/Restrictions
The originally examined claims were directed to products, namely pharmaceutical compositions comprising “gilteritibib” as an active ingredient” (previously examined claims 11-18), and a screening method, which recited
19. A method for examining whether gilteritinib exerts an effect on a patient with an ALK fusion-gene positive tumor, including:
examining whether a kinase domain of ALK is a wild type or has at least one ALK mutation of T1151K, C1156Y, I1171N, I1171T, I1171S, F1174I, F1174V, V1180L, L1196M, L1196Q, L1198F, D1203N, F1245V, L1256F or G1269A; and
determining that gilteritinib is effective when any one of the above present.
Accordingly, the previously presented screening method was previously examined on record.
In the claim set filed 6/25/2026, Applicant substantially amended claim 19 and added new claims 20-32. Examiner directs Applicant to MPEP §§ 818, 818.02(a), 819, and 821.
Newly submitted claims 26-32 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Inventions of claims 19-25 and the invention of claims 26-32 are directed to related but distinct processes. The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed have a materially different design, mode of operation, function or effect, do not overlap in scope, and are not obvious variants because claims 26-32 are directed to a different purpose (treatment rather than diagnostic screening), utilize different steps (e.g., administration of gilteritinib to a subject), and do not require, per se, a screening or detecting step). Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants.
Since applicant has received an action on the merits for the originally presented invention (original claim 19), this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 26-32 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Newly submitted claims 20-22 and 25 are directed to species of invention that are independent or distinct from the invention originally claimed for the following reasons: The amended claims are directed to different species that recite the mutually exclusive characteristics of such species, including the detection of one or more “compound mutations” (see, e.g., claims 19, 21-22); detecting “whether or not the ALK fusion-gene positive tumor is a tumor having echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene” (see, e.g., claims 20); detecting mutations such as L1198H (see, e.g., claims 19, 24); or otherwise wherein “the ALK fusion gene positive tumor is a non-small cell lung cancer” (see, e.g., claim 25). Accordingly, claims 20-22 and 25 are directed to different species that are understood to recite mutually exclusive characteristics, and therefore be directed to species that were not originally presented.
The originally presented species is understood to be a screening method requiring detection of a single mutation in an ALK fusion-gene positive tumor selected from T1151K, C1156Y, I1171N, I1171T, I1171S, F1174I, F1174V, V1180L, L1196M, L1196Q, L1198F, D1203N, F1245V, L1256F or G1269A.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 20-22 and 25 withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 20-22 and 25-32 are presently withdrawn by original presentation.
Claims 19 and 23-24 are presently considered and rejected in view of the prior art of record, as explained below.
Priority
The priority claim to PCT/JP2022/005499 (filed 2/11/2022) is acknowledged.
Examiner notes that no certified translation of the Foreign Application JP2021-020640 (filed 2/12/2021) has been placed on record. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file. See 37 CFR 41.154(b).
Information Disclosure Statement
The IDS filed 3/31/2026 is acknowledged and presently considered.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Amended claim 19 is representative of the pending claim scope:
19. (Currently Amended) A method for determining whether gilteritinib exerts an effect on a patient with an anaplastic lymphoma kinase (ALK) fusion-gene positive tumor, comprising:
detecting whether or not the ALK fusion-gene positive tumor has:
compound mutations in I1171N, I1171S, V1180L, L1196M or C1156Y;
at least two compound mutations including mutations in I1171N/S/T, F1174I/L, L1196M, L1198F/H, G1202R, D1203N, F1245V, L1256F and G1269A; or
at least one ALK mutation in T1151K, C1156Y, I1171N, I1171T, I1171S, F1174I, F1174V, V1180L, L1196M, L1196Q, L1198F, D1203N, F1245V, L1256F or G1269A; and
determining that gilteritinib has a therapeutic effect on the ALK fusion-gene positive tumor based on the detection of any one of the above .
Applicable claim interpretation is set forth below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
At claim 19 the phrase “patient with an [ALK] fusion-gene positive tumor” is understood to refer to a subset of cancers driven by a specific genetic rearrangement where the ALK gene fuses with another gene (see, e.g., Spec. filed 8/02/2023 at ¶[0004]).
Amended claim 19 was presumably amended to overcome a prior rejection under 35 USC § 112(b), by amending claim 19 to recite “determining that gilteritinib has a therapeutic effect on the ALK fusion-gene positive tumor based on the detection of any one of the above”. Accordingly, the “determining” step is now understood to be a mental conclusion “based on the detection of any one of the above” mutations. Accordingly, “detection” of an enumerated mutation is understood to satisfy the pending claim scope.
Additional claim interpretations are discussed below.
Drawings
The drawings filed 6/25/2026 are acknowledged and accepted.
Withdrawn Claim Rejections
The rejection of claims 13 and 19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, is withdrawn in view of the amendments to claim 19 and the cancellation of claim 13.
The rejection of claims 11-18 under 35 U.S.C. 102(a)(1) as being clearly anticipated by Lee et al.1 is withdrawn as moot in view of the cancellation of claims 11-18 and all claims directed to products.
The rejection of claims 11-18 under 35 U.S.C. 102(a)(1)/(a)(2) as being clearly anticipated by US2019/0262328 (Aug. 29, 2019), is withdrawn as moot in view of the cancellation of claims 11-18 and all claims directed to products.
The rejection of claim 19 under 35 U.S.C. 103 as being unpatentable over US2019/0262328 (Aug. 29, 2019) as applied to claims 11-18 above, and further in view of Katayama et al.2 is withdrawn in view of the amendments to claim 19 as filed 6/25/2026, but those amendments have necessitated a revised rejection as set forth below.
New or Revised Claim Rejections Necessitated by Applicant Amendment
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 19 and 23-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Legal Guidance
The U.S. Patent and Trademark Office recently published revised guidance on the application of § 1013 (“2019 Guidance”). Under that guidance, in determining what concept the claim is “directed to,” the Office looks to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
In the instance that a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, the Office then performs a further inquiry as to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82), and thereby consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See 2019 Guidance.
Claim Interpretation
The claim scope is represented by the following independent claim:
19. (Currently Amended) A method for determining whether gilteritinib exerts an effect on a patient with an anaplastic lymphoma kinase (ALK) fusion-gene positive tumor, comprising:
detecting whether or not the ALK fusion-gene positive tumor has:
compound mutations in I1171N, I1171S, V1180L, L1196M or C1156Y;
at least two compound mutations including mutations in I1171N/S/T, F1174I/L, L1196M, L1198F/H, G1202R, D1203N, F1245V, L1256F and G1269A; or
at least one ALK mutation in T1151K, C1156Y, I1171N, I1171T, I1171S, F1174I, F1174V, V1180L, L1196M, L1196Q, L1198F, D1203N, F1245V, L1256F or G1269A; and
determining that gilteritinib has a therapeutic effect on the ALK fusion-gene positive tumor based on the detection of any one of the above .
Accordingly, the pending claim scope is directed to a “method of determining”, wherein the method includes a step of “detecting” a naturally-occurring mutation, and ostensibly includes a step of “determining that gilteritinib has a therapeutic effect on the ALK fusion gene positive tumor based on the detection of any one of the above [mutations]”. However, the “determining” step is now expressly “based on the detection of any one of the above” mutations, and does not recite nor require anything more than “detection of any one of the above” mutations. Therefore, the second step of “determining” is fully satisfied “based on the detection of any one of the above mutations”, and is therefore understood to be a mental conclusion drawn following “detection of any one of the above mutations”.
Prong 2A
The claims are directed to a natural relationship and law of nature (i.e., a correlation between naturally-occurring mutations present in an ALK fusion-gene positive tumor, and a mental determination that “gilteritinib has a therapeutic effect on the ALK fusion-gene positive tumor based on the detection of any one of the above” mutations) is a law of nature and natural phenomenon. Similar concepts have been held by the courts to constitute law of nature/ natural phenomena, as in the identification of a correlation between the presence of a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017). In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012).
The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77), namely the relationship between the naturally occurring mutations in ALK fusion-gene positive tumors and the activity of gilteritinib.
This relationship and correlation between mutations and susceptibility to treatments is a judicial exception as it exists in principle apart from any human action; the correlation itself therefore cannot form the basis for eligibility. Similarly, it is a naturally occurring phenomenon that mutations convey resistance to some but not all treatments.
Furthermore, the claimed step of “determining that gilteritinib has a therapeutic effect on the ALK fusion gene positive tumor based on the detection of any one of the above [mutations]” may also be categorized as an abstract idea, namely a mental processes/ concepts performed in the human mind, because it is a conclusion “based on the detection of any one of the above [mutations] and therefore may occur solely within the human mind, or by a human using pen and paper. Accordingly, the “determining” step is understood to be a “mental” conclusion drawn from the step of “detecting” any one of the naturally occurring mutations.
Accordingly, the claims are understood to be directed to a law of nature and natural phenomenon, namely the presence or absence of naturally-occurring mutations, wherein if the mutations are present, a mental conclusion is drawn that “gilteritinib has a therapeutic effect” of some undisclosed, general level.
Prong 2B
The additional elements of the claims do not add significantly more to the judicial exception(s), because the pending claims do not define “detecting” or “determining” in a manner that required more than the limitations discussed above, namely the detection of naturally-occurring mutations.
In this case, it was well-understood, routine and conventional to simply screen for the presence or absence of such mutations in such patients (see, e.g., Katayama et al.4 at 5686 at col II at 1st full ¶, 5690 at col I at 1st full ¶ to col II at 1st partial ¶, identifying that that the mutations of V1180L, L1196M, and I1171T were already known in the art and understood to mediate resistance to alectinib and crizotinib; see also Noé et al.5 at title, abs, 602 at col I at 2nd full ¶. 602 at col II at § “Mutation Analysis”, 603 at col I at § ALK Mutations Observed”, Table 1 on 603, Fig. 2 on 604, Table 3 on 606, explaining that methods of detecting the specific mutations of C1156Y, F1174V, I1171N, I1171S, G1202R, and G1269A in ALK-positive NSCLC patients was already known and routine in the prior art, and that such mutations were already associated with resistance to alectinib and/or crizotinib). Accordingly, performing known detection steps to detect known mutations in a known patient population, wherein the known mutations were explicitly utilized to identify drug resistance in such patients, is routine, conventional, and well-understood in the art.
In view of the above evidence, the claimed steps of determining the presence of known mutations using known methods of detection do not add any feature that is more than well-understood, purely conventional, or routine in the field of diagnostics and biochemical assay methodologies.
Furthermore, every application of the judicial exception would require determination of the presence of naturally occurring mutations within the recited patient population. Limitations that are necessary for all practical applications of a judicial exception, such that everyone practicing the judicial exception would be required to perform those steps or every product embodying that judicial exception would be required to include those features, would not be sufficient to confer patent eligibility. In this case, everyone practicing the judicial exception would need to determine if a naturally occurring mutation was present or absent in the recited patient population.
When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or a transformation of a particular article, in this step that distinguishes it from well-understood, routine, and conventional data gathering activity engaged in by scientists prior to applicant’s invention, and at the time the application was filed, e.g., the routine and conventional techniques of detecting a protein using an antibody to that protein. See also MPEP 2106.05(g).
Appending a generic, routine, and obvious post-solution treatment step or mental conclusion does not provide a sufficient inventive concept to satisfy § 101. As was the case in Mayo and Ariosa, the method claims at issue here amount to "nothing significantly more than an instruction to doctors to apply the applicable laws when treating their patients" using "conventional steps, specified at a high level of generality." Mayo, 132 S. Ct. at 1298, 1300; Ariosa, 788 F.3d at 1377-78.
Accordingly, the additional steps/ elements in the claim, when considered alone or in combination, are insufficient to add significantly more.
Conclusion
For all of the reasons discussed above, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s). The additional steps also fail to effect a transformation or reduction of a particular article into a different state or thing; nor do they involve the use of a particular machine. For all these reasons, claims 19 and 23-24 are rejected under 35 U.S.C. 101.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 19 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over US2019/0262328 (Aug. 29, 2019) in view of Katayama et al.6
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
US’328 discloses that gilteritinib was a known prior art element and art-recognized CYP3A4 substrate drug (see, e.g., US’328 at ¶¶[0012], [0301], Table 1 at col. 35, claims 1-2 and 16). Regarding amended claims 19 and 23-24, US’328 explicitly teaches and claims methods directing artisans to treat patients in need thereof with a CYP3A4 substrate drug (see, e.g., US’328 at claim 1), wherein the CYP3A4 substrate drug may be gilteritinib (see, e.g., US’328 at claim 2), and wherein the “patients in need thereof” expressly include patients “with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on” either crizotinib and/or alectinib (see, e.g., US’328 at claim 16, ¶[0317] at 76 at col I). Accordingly, an artisan would have already known, expected, predicted, and concluded that gilteritinib administration would be an “effective” treatment for all such patients having (ALK)-positive NSCLC in view of US’328 because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), absent objective evidence to the contrary.
US’328 differs from the scope of instant claim 19 as follows: Although US’328 claims and renders obvious methods of administering gilteritinib to treat patients (ALK)-positive NSCLC, and renders obvious a “determination” that gilteritinib is effective to treat such patients, US’328 does not teach a screening step requiring “detecting whether or not the ALK fusion-gene positive tumor has at least one ALK mutation, such as I1171T, V1180L, or L1196M.
However, Katayama identifies that, it was already known, circa 2014, that although crizotinib was a standard therapy for patients with ALK-rearranged NSCLC, that patients could relapse and become crizotinib-resistance (see, e.g., Katayama at title, abs, 5687 at box). Katayama also tests models of alectinib resistance (see id.). Katayama identifies that mutations in ALK cause patients to “eventually develop resistance to next-generation inhibitors” (see id. at 5686 at col II at 1st full ¶), and identifies that the mutations of V1180L, L1196M, and I1171T mediate resistance to alectinib and crizotinib (see id. at 5686 at col II at 1st full ¶, 5690 at col I at 1st full ¶ to col II at 1st partial ¶). Katayama identifies that ALK-rearranged NSCLC patients were identified as having a I1171T mutation during a course of alectinib treatment and following a durable response to crizotinib (see, e.g., Katayama at 5695 at col I at 1st full ¶ to col II at 1st partial ¶).
Accordingly, the patient population of patients with ALK-positive NSCLC “who had progressed on or are intolerant to crizotinib” and (ALK)-positive NSCLC “whose disease has progressed on crizotinib and and at least one other ALK inhibitor” as disclosed by the primary reference (see, e.g., US’328 at claim 16, ¶[0317] at 76 at col I) were known in the prior art, and understood to include patients having at least a I1171T mutation (see, e.g., Katayama at 5695 at col I at 1st full ¶ to col II at 1st partial ¶).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is obvious because it is the application or combination of known patient screening techniques for I1171T mutations in ALK-positive NSCLC patients, with the treatment of such patients with gilteritinib as taught by the primary reference, wherein administration of gilteritinib would be predicted and expected to successfully treat such ALK-positive NSCLC (i.e., it would be “determined” to be “effective” to some extent); such a combination would predictably help patients obtain more effective treatments once a mutation associated with resistance to alectinib and crizotinib was detected (see, e.g., MPEP §§ 2143(I)(A), (C), (D), (F), and (G)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to screen patients for known mutations and to perform a known method on a known patient population by administering a known compound to the patients to achieve a known outcome.
Accordingly, claim 19 and 23 are rejected.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over US2019/0262328 (Aug. 29, 2019) in view of Katayama et al.7 as applied to claims 19 and 23 above, and further in view of Noé et al.8.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of US2019/0262328 in view of Katayama et al. as applied to claims 19 and 23 has been set forth above in a preceding rejection, and those teachings are incorporated herein.
US’328 and Katayama differ from the scope of newly added claim 24 as follows: Newly added claim 24 recites a subgenus of ALK mutations excluding the mutations of V1180L, L1196M, or I1171T, and instead claim 24 recites other single mutations such as C1156Y, F1174V, and G1269A, which were not taught or disclosed by US’328 or Katayama.
However, circa 2019, artisans were well aware of methods of detecting mutations such as C1156Y, F1174V, and G1269A in ALK-positive NSCLC patients (see, e.g., Noe at title, abs, 602 at col I at 2nd full ¶. 602 at col II at § “Mutation Analysis”, 603 at col I at § ALK Mutations Observed”, Table 1 on 603, Fig. 2 on 604). Furthermore, artisans were aware, circa 2019, that the mutations of C1156Y, F1174V, and G1269A were each associated with Crizotinib resistance (see, e.g., Noe at Table 1 on 603), and that I1171N, I1171S, and G1202R mutations were each associated with Alectinib resistance (see, e.g., Noe at Table 3 on 606). In addition, Noe notes that plasma genotyping may be helpful to identify patients with resistant mutations (see, e.g., Noe at Table 3 on 607).
In sum, genotyping ALK-Positive NSCLC patients and specifically looking for mutations associated with Crizotinib resistance and Alectinib resistance, permits practitioners to treat such patients using other art-recognized compounds suitable for treating ALK-positive NSCLC that such patients are not resistant to already. Specifically, US’328 explicitly teaches and claims methods directing artisans to treat patients in need thereof with a CYP3A4 substrate drug (see, e.g., US’328 at claim 1), wherein the CYP3A4 substrate drug may be gilteritinib (see, e.g., US’328 at claim 2), and wherein the “patients in need thereof” expressly include patients “with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on” either crizotinib and/or alectinib (see, e.g., US’328 at claim 16, ¶[0317] at 76 at col I). Accordingly, in combination, such prior art readily informs artisans that such patients may be desirably screened for the presence of mutations that convey resistance to Crizotinib and/or Alectinib , and if present, an artisan would reasonably appreciate that such patients should be treated with a compound other than crizotinib and/or alectinib, wherein such other compound may be gilteritinib (see, e.g., US’328 at claim 2, 16, ¶[0317] at 76 at col I).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is obvious because it is the application or combination of known patient screening techniques for known mutations that convey resistance to crizotinib and/or alectinib in (e.g., C1156Y, F1174V, G1269A, I1171N, I1171S, and/or G1202R) ALK-positive NSCLC patients, combined with a known treatment for such patients with resistance to crizotinib and/or alectinib, namely gilteritinib, as taught and disclosed by the primary reference; accordingly screening a known patient population for known resistance mutations, and then treating a patient using a known treatment that the patient is not resistant to, is obvious in view of the prior art because such a combination of screening steps and treatments would predictably help patients obtain more effective treatments once a mutation associated with resistance to alectinib and crizotinib was detected (see, e.g., MPEP §§ 2143(I)(A), (C), (D), (F), and (G)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to screen patients for known mutations and to perform a known method on a known patient population by administering a known compound to the patients to achieve a known outcome.
Accordingly, claims 24 is rejected as obvious.
Response to Arguments
Applicant's arguments filed 6/25/2026 have been fully considered but they are not persuasive and are substantially rendered moot. Remaining applicable arguments are addressed below.
Applicable arguments pertaining to the revised 103 rejection in view of US’328 and Srinivasan are raised at pages 7-8 (see, e.g., Reply filed 6/25/2026 at 7 at 3rd full ¶ to page 8 at 6th full ¶). These arguments have been fully considered but not found persuasive for the reasons explained below.
It is the Examiner’s understanding that Applicant is alleging that US’328 (a.k.a., Srinivasan), considered alone, does not teach “the specific mutations” recited at instant claims 19 and 23-24 (see, e.g., Reply filed 6/25/2026 at 7 at final ¶ to page 8 at 1st full ¶); in addition, it is the Examiner’s understanding that Applicant is alleging that Katayama et al., considered alone, “fails to mention anything about gilteritinib” (see, e.g., Reply filed 6/25/2026 at 8 at 2nd full ¶). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Here, it is neither disputed nor dispositive of obviousness that neither individual reference anticipates the pending claims, because no rejection based upon a single reference anticipating the claims has been set forth on record. Rather, here, the teachings of each individual reference is undisputed, and therefore the prior art, taken as a whole, teaches all claimed limitations recited in the amended and newly added claims. Accordingly, such arguments are not persuasive.
It is the Examiner’s understanding that Applicant is generally alleging that prima facie obviousness was not established because the prior art does not teach or suggest a “core feature” (see, e.g., Reply filed 6/25/2026 at 7 at penultimate ¶), or otherwise teach that “gilteritinib has a therapeutic effect on the ALK fusion-gene positive tumor based on the detection of the specific mutations as recited in claim 19 as amended” (see, e.g., Reply filed 6/25/2026 at 8 at 3rd to 4th full ¶¶). First, Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references. Second, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “based on the detection”, “due to specific mutaitons” ) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Third, Applicant fails to identify a single, claimed aspect that was not fully addressed in the prior art. Fourth, Applicant does not acknowledge or address the rationales relied upon by the Examiner that support a determination of obviousness under MPEP §§ 2143(I)(A), (C), (D), (F), and (G). As noted in the rejection, the pending claims are the obvious application or combination of known patient screening techniques for I1171T mutations in ALK-positive NSCLC patients, wherein gilteritinib would have already been readily predicted and expected to successfully treat the exact same patient population of ALK-positive NSCLC patients (i.e., it would be “determined” to be “effective” to some extent, and wherein such patients would be screened for such mutations to predictably and expectedly help such patients obtain more effective treatments (i.e., with gilteritinib) because such mutations were known to be associated with resistance to alectinib and crizotinib. In sum, such arguments are not persuasive because they amount to a dismissal of the facts and rationales relied upon by the Examiner to support a determination of obviousness.
Accordingly, all applicable arguments have been fully considered but not found persuasive. Therefore, the claims remain rejected in view of the new and revised rejections set forth above, which were necessitated by Applicant’s amendments.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Takahashi et al.9 pertains to known mutations in ALK positive cancers that cause resistance to cancer therapeutics (see, e.g., Takahashi at title, abs). Takahashi explicitly identifies known ALK mutations causing resistance (see, e.g., Takahashi at title, abs, 582 at col I at 1st ¶). Accordingly, screening ALK patients for known mutations associated with drug resistance would be apparent to one of skill in the art to facilitate individualized and effective treatments.
Holla et al.10 pertains to known mutations in ALK-positive cancers associated with drug resistance (see, e.g., Holla at title, abs, passim). Accordingly, screening ALK patients for known mutations associated with drug resistance would be apparent to one of skill in the art to facilitate individualized and effective treatments.
Kuravi et al.11, pertains to the treatment of NPM1-ALK-driven ALCL with Gilteritinib (see, e.g., Kuravi at title, abs, passim).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new and/or revised ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 Lee et al., Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor. Blood. 2017 Jan 12;129(2):257-260. doi: 10.1182/blood-2016-10-745133. Epub 2016 Dec 1. PMID: 27908881; PMCID: PMC5234222; hereafter “Lee”.
2 Katayama et al., Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res. 2014 Nov 15;20(22):5686-96. doi: 10.1158/1078-0432.CCR-14-1511. Epub 2014 Sep 16. PMID: 25228534; PMCID: PMC4233168; hereafter Katayama.
3 2019 Revised Patent Subject Matter Eligibility Guidance, 84 Fed. Reg. 50-57 (January 7, 2019)
4 Katayama et al., Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res. 2014 Nov 15;20(22):5686-96. doi: 10.1158/1078-0432.CCR-14-1511. Epub 2014 Sep 16. PMID: 25228534; PMCID: PMC4233168; hereafter Katayama; cited in previous action.
5 Noé et al., ALK Mutation Status Before and After Alectinib Treatment in Locally Advanced or Metastatic ALK-Positive NSCLC: Pooled Analysis of Two Prospective Trials. J Thorac Oncol. 2020 Apr;15(4):601-608. doi: 10.1016/j.jtho.2019.10.015. Epub 2019 Nov 9. PMID: 31712133.
6 Katayama et al., Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res. 2014 Nov 15;20(22):5686-96. doi: 10.1158/1078-0432.CCR-14-1511. Epub 2014 Sep 16. PMID: 25228534; PMCID: PMC4233168; hereafter Katayama.
7 Katayama et al., Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib. Clin Cancer Res. 2014 Nov 15;20(22):5686-96. doi: 10.1158/1078-0432.CCR-14-1511. Epub 2014 Sep 16. PMID: 25228534; PMCID: PMC4233168; hereafter Katayama.
8 Noé et al., ALK Mutation Status Before and After Alectinib Treatment in Locally Advanced or Metastatic ALK-Positive NSCLC: Pooled Analysis of Two Prospective Trials. J Thorac Oncol. 2020 Apr;15(4):601-608. doi: 10.1016/j.jtho.2019.10.015. Epub 2019 Nov 9. PMID: 31712133.
9 Takahashi et al., Overcoming resistance by ALK compound mutation (I1171S + G1269A) after sequential treatment of multiple ALK inhibitors in non-small cell lung cancer. Thorac Cancer. 2020 Mar;11(3):581-587. doi: 10.1111/1759-7714.13299. Epub 2020 Jan 13. PMID: 31943796; PMCID: PMC7049522; hereafter “Takahashi”; cited in previous action.
10 Holla et al., ALK: a tyrosine kinase target for cancer therapy. Cold Spring Harb Mol Case Stud. 2017 Jan;3(1):a001115. doi: 10.1101/mcs.a001115. PMID: 28050598; PMCID: PMC5171696; hereafter “Holla”; cited in previous action.
11 Kuravi et al., Preclinical Evaluation of Gilteritinib on NPM1-ALK-Driven Anaplastic Large Cell Lymphoma Cells. Mol Cancer Res. 2021 May;19(5):913-920. doi: 10.1158/1541-7786.MCR-20-0738. Epub 2021 Jan 29. PMID: 33514657; PMCID: PMC9135172; hereafter Kuravi; cited in previous action.
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