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 .
DETAILED ACTION
This Office Action is responsive to the Response to Election/Restriction filed 07/15/2026.
The preliminary amendments filed 12/19/2024 and 12/12/2025, amended claims 1, 4, 6, 9, 12, 16-18, 21, and 42, deleted claims 15, 19-20, 22-41 and 43-66, and added claim 67.
Claims 1-14, 16-18, 21, 42 and 67 are pending.
Priority
This application claims the following priority:
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Specification
The disclosure is objected to because of the following informalities:
On pg. 22, line 8, a US Patent is recited as “U.S. Pat. No. 9,249,.,” which is an incomplete patent number.
Appropriate correction is required.
Election/Restrictions
Applicant’s election without traverse of Group I, and LC-2 as the PROTAC therapeutic agent and Lapatinib as the ABC transporter/kinase inhibitor or dual ABC transporter/kinase inhibitor, in the reply filed on 07/15/2026, is acknowledged.
Note: The instant specification teaches lapatinib as a dual ABC transporter/kinase inhibitor. As such, lapatinib is elected as the ABC transporter inhibitor or dual ABC transporter/kinase inhibitor.
In the course of the search, the ABC transporter/kinase inhibitor or dual ABC transporter/kinase inhibitor, was expanded to include RAD001, which is everolimus, a dual ABC transporter/kinase inhibitor
Claims 2, 6-13, 21 and 42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and subject matter, there being no allowable generic or linking claim.
Claims 1, 3-5, 14, 16-18, and 67 are examined on the merits herein.
Claim Rejections - 35 USC § 112(b)
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.
Claim 18 is 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.
-Claim 18 depends from claim 1, wherein claim 1 recites “one or more ABC transporter inhibitors, or one or more dual ABC transporter/kinase inhibitors.” Claim 18 recites “linked to a kinase inhibitor, an ABC transporter inhibitor or a dual ABC transporter/kinase inhibitor,” which renders the claim indefinite. It is not clear if the “kinase inhibitor” is distinct from the “ABC transporter/kinase inhibitor” or if the “kinase inhibitor” is the “ABC transporter/kinase inhibitor.”
In view of compact prosecution, for the purpose of applying prior art, “linked to a kinase inhibitor, an ABC transporter inhibitor” in claim 18, is interpreted as “linked to an ABC transporter inhibitor.”
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1, 3-5, 14, 16, and 67 are rejected under 35 U.S.C. 103 as being unpatentable over WO2021/06189 to Gray (published 04/01/2021, IDS of 03/09/2026).
Gray teaches pharmaceutical compositions comprising PROTAC therapeutic agents and a pharmaceutically acceptable carrier (pgs. 112, 138-claims 1, 35).
Regarding claims 1 and 3, Gray differs from that of instant claims 1 and 3 in that it does not explicitly teach a pharmaceutical composition comprising the PROTAC therapeutic agent and a dual ABC transporter/kinase inhibitor.
Gray teaches that in some embodiments, its compounds can be used in combination with other anti-cancer agents, such as everolimus (RAD001) for the treatment of head and neck cancer, alectinib, crizotinib or ceritinib for the treatment of non-metastatic or metastatic lung cancer, NSCLC, lung adenocarcinoma and a squamous cell lung carcinoma, or axitinib for advanced solid tumors, wherein everolimus is a dual ABC transporter/kinase inhibitor ([00149]).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to add everolimus to the composition of Gray, to arrive at instant claims 1 and 3. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-Gray teaches that other anti-cancer agents can be added to its compositions,
-Gray specially teaches everolimus as an anti-cancer agent that can be added to its compositions for the treatment of head and neck cancers.
As such, an ordinary skilled artisan would have been motivated to make such an addition, to predictably arrive at a composition that more effectively treats cancer, and in particular, head and neck cancer.
Regarding claims 4 and 14, Gray teaches its compounds as binding extracellular-signal-regulated kinase 5 (ERK5), causing degradation of ERK5 ([0004], [0008]). ERK5 is activated by the upstream kinase MEK5 and is a key integrator of cellular signal transduction, playing a crucial role in various cellular processes such as proliferation, differentiation, apoptosis and cell survival. Since the PROTAC of Gray is activated by the MEK5, and is used for the same purpose (to treat cancer) and in the same dosage amounts (Gray teaches dosages of about 0.001 to about 600mg in [00122], and the instant specification teaches about 1mg to about 100mg on pg. 44), the PROTAC of Gray necessarily targets the EGFR-KRAS-PI3K-MEK signaling pathway. Thus, while the prior art does not explicitly teach these properties, burden is on Applicant to show that the prior art does not have these properties.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Regarding claims 5 and 16, Gray teaches its compounds as targeting ERK and MEK ([0003]).
Further regarding claim 14, everolimus is RAD001.
Regarding claim 67, Gray does not teach its PROTAC as a BET or CDK9 PROTAC. As such, this limitation is considered to be met.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over WO2021/06189 to Gray (published 04/01/2021, IDS of 03/09/2026), as applied to claims 1, 3-5, 14, 16, and 67 above, and further in view of Yang (The Role of Autophagy in Cancer: Therapeutic Implications, published 2011, PTO-892).
Gray is applied as discussed above and incorporated herein.
While Gray teaches a pharmaceutical composition comprising PROTAC and dual ABC transport inhibitor/kinase, it differs from that of instant claim 17 in that it does not teach an autophagy inhibitor.
Gray teaches autophagy inhibitors as additional therapeutics that can be added to its compositions ([00146]).
Yang teaches that inhibition of autophagy restores chemosensitivity and enhances tumor cell death by diverse anticancer therapies (abstract; pg. 1539, Conclusions).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to add an autophagy inhibitor, to the composition of Gray, to arrive at instant claim 17. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, because:
-Gray teaches that autophagy inhibitors can be added to its compositions, and
-Yang teaches that autophagy inhibitors restore chemosensitivity and enhance tumor cell death by diverse anticancer therapies.
As such, an ordinary skilled artisan would have been motivated to make such an addition, to predictably arrive at a composition that restores chemosensitivity and enhances tumor cell death by diverse anticancer therapies, thereby increases the therapeutic effectiveness of the composition.
Note: The below rejection is applied in view of the Election of LC-2 as the PROTAC therapeutic agent and lapatinib as the dual ABC transporter/kinase inhibitor.
Claims 1, 3-5, 14, 16, and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Bond (Targeted Degradation of Oncogenic KRASG12C by VHL-Recruiting PROTACs, published 2020, PTO-892) in view of Burris (A Phase I and Pharmacokinetic Study of Oral Lapatinib Administered Once or Twice Daily in Patients with Solid Malignancies, published 2009, PTO-892).
Bond teaches LC-2 as the first PROTAC capable of degrading endogenous KRASG12C for attenuating oncogenic KRAS levels and downstream signaling in cancer cells (abstract).
Bond teaches the KRAS p.G12C mutation as highly prevalent in lung adenocarcinoma (LUAD), and as found in colorectal cancers and 1% of all other solid tumors (pg. 1367, paragraph spanning the columns).
Regarding claims 1 and 3, while Bond teaches a composition comprising LC-2, a PROTAC therapeutical agent, it does not teach a dual ABC transporter/kinase inhibitor.
Burris teaches lapatinib, an erb1 and erb2 tyrosine kinase inhibitor, as a well-tolerated anti-cancer agent that is effective to treat solid malignancies (abstract, pg. 6702).
Burris teaches lapatinib as resulting in stable disease of greater than 10 months in patients with lung cancer, such as non-small cell lung cancer (abstract; pg. 6705, Col. 2 “Tumor response”). Burris teaches non-small cell lung cancer, a subtype of lung adenocarcinoma, as associated with the overexpression of erb1 and erb2, wherein such patients have poor prognoses and reduced survival (pg. 6702).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to combine the composition comprising LC-2 of Bond and the composition comprising lapatinib of Burris, to arrive at instant claims 1 and 3. One of ordinary skill in the art would have been motivated to make such a combination, with a reasonable expectation of success, because:
-Bond teaches LC-2 as effective in treating KRAS p.G12C mutation cancer, which are highly prevalent in lung adenocarcinoma (LUAD),
-Bond teaches lapatinib as effective in stabilizing disease and increasing survival in patients with non-small cell lung cancer, a type of lung adenocarcinoma, and
-"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980), MPEP 2144.06.
As such, an ordinary skilled artisan would have been motivated to make such a combination to predictably arrive at an effective method of treating KRAS mutated non-small cell lung cancer, which more effectively treats the cancer by stabilizing the disease and increasing survival.
Regarding claims 4 and 14, Bond teaches LC-2 as attenuating KRAS levels. Since the PROTAC of Bond attenuates KRAS levels, and is used for the same purpose (to treat cancer), in therapeutically effective amounts to treat cancer, the PROTAC of Bond necessarily targets the EGFR-KRAS-PI3K-MEK signaling pathway. Thus, while the prior art does not explicitly teach these properties, burden is on Applicant to show that the prior art does not have these properties.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Regarding claims 5 and 16, Bond teaches LC-2 as inhibiting KRAS and Burris teaches lapatinib as an inhibitor of EGFR (pg. 6702, 1st paragraph).
Regarding claim 67, Bond does not teach its PROTAC as a BET or CDK9 PROTAC. As such, this limitation is considered to be met.
Free of the Prior Art
Claim 18 appears to be free of the prior art, though due to its indefinite nature, it is not clear if claim 18 is free of the prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Examiner, Art Unit 1622
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