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 1-15, 21, 23, 24, 65 and 66 are pending and currently under consideration.
Claim Rejections - 35 USC § 112
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 1-12, 65, and 66 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, because 35 U.S.C. 112(b) and 35 U.S.C. 112 (pre-AIA ), second paragraph, require claims to particularly point-out and distinctly claim subject matter. The instant claims attempt to incorporate by reference to a specific table or figure (see “Table 1” of claim 1); however, such incorporation is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. In the instant case, there is a practical way to define the invention in words. Incorporation by reference is a necessity doctrine, not for applicant’s convenience. See MPEP 2173.05(s).
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 1-12, 15, 23, 24, 65, and 66 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 methods of downregulating expression or activity of (a) Kras G12D and (b) just any signaling molecule from Table 1 by administering inhibitors of (a) and (b), does not reasonably provide enablement for “synergistically” inhibiting proliferation by just any means of downregulating expression or activity of (a) and (b) in just any cell type. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to perform the invention commensurate in scope with these claims. Similar to claims at issue in Amgen Inc. v Sanofi, the instant specification does not enable the full scope of the claims.
Factors to be considered in determining whether undue experimentation is required are summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed.
The instant claims are drawn to “synergistically” inhibiting proliferation by just any means of downregulating expression or activity of (a) Kras G12D and (b) just any signaling molecule from Table 1 in just any cell type. This includes methods of synergistically inhibiting proliferation comprising contacting just any cancer cell type with a combination of a particular inhibitor of Kras G12D and a particular inhibitor of a signaling molecule of Table 1 that has yet to be shown to synergistically inhibit proliferation, as claimed.
This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The specification discloses synergistically inhibiting proliferation comprising contacting cancer cells expressing Kras G12D with a combination of a particular inhibitor of Kras G12D (“Compound A”, “Compound B”, or “Compound C” – which are not structurally defined) and a particular inhibitor of a signaling molecule of Table 1 (Figures 1B, 2B, 3B, 4B, 5B, 6B, and 7B, in particular). The specification further discloses that not every combination of a particular inhibitor of Kras G12D and a particular inhibitor of a signaling molecule of Table 1 synergistically inhibits proliferation of a given cell. For instances, no combination of (i) the Kras G12D inhibitor Compound C and (ii) MEK inhibitor Trametinib, CDK4/6 inhibitor Palbociclib, or PI3Ka inhibitor BYL719 result in “synergistic” inhibition of proliferation of ASPC1 pancreatic cancer cells (Figure 1B). Further, no data is provided inhibiting (i) any Kras G12D and (ii) signaling molecules such as “AXL or a mutant thereof”, “ROS1 or a mutant thereof”, or “RET or a mutant thereof” of Table 1.
The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.”Ariad Pharmaceuticals, Inc. v. EliLilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are broadly drawn to “synergistically” inhibiting proliferation by just any means of downregulating expression or activity of (a) Kras G12D and (b) just any signaling molecule from Table 1 in just any cell type, and Applicant has not enabled said method because it has not been shown which means (such as which particular combinations of inhibitors) of downregulating (a) and (b) result, or do not result, in synergistically inhibiting proliferation. Undue experimentation would be required to determine which particular combinations of (i) particular inhibitor(s) of Kras G12D and (b) particular inhibitor(s) of signaling molecule(s) of Table 1 result, or do not result, in synergistic inhibition of a particular type of cell in order perform the method as broadly claimed.
In view of the teachings above and the lack of guidance, workable examples and or exemplification in the specification, it would require undue experimentation by one of skill in the art to determine with any predictability, that the method would function as claimed.
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)(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) 1-6, 8, 65, and 66 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ganesh (WO 2020/205473 A1; 10/08/2020).
Ganesh teaches treating pancreatic cancer Kras G12D (Pan02 tumors) with the Kras G12D inhibitor KRAS/LNP results in reduced cell growth (Figure 7, in particular). Ganesh teaches treating subjects with pancreatic cancer tumors comprising a Kras G12D (Pan02 tumors) by administering to the subjects the MEK inhibitor trametinib followed by the Kras G12D inhibitor KRAS/LNP reduces tumor volume (see Example 3, page 54 of Example 5, and Figure 10A, in particular). Although Ganesh does not specifically teach administering the MEK inhibitor trametinib and the Kras G12D inhibitor KRAS/LNP to pancreatic cancer cells with Kras G12D results in synergistic inhibition of proliferation of the cells or reduced Ras signaling output of the tumor cells, the claimed method appears to be the same as the prior art, absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the method of the prior art does not possess the same material, structural and steps-like characteristics of the claimed method. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed method is different from that 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 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Claim Rejections - 35 USC § 102/103
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.
Claim(s) 1-15, 65, and 66 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Aay et al (US 2022/0105185 A1; 4/7/2022).
Aay et al teaches a method of treating Kras-G12D expressing cancer cells in a subject comprising contacting the cells with effective amounts of compounds that inhibit Kras-G12D by administering the compounds to the subject ([0326]-[0328] and claim 112, in particular). Aay et al further teaches said method wherein the cells are pancreatic cancer cells, colorectal cancer cells, or NSCLC cells ([0327]-[0328] and claims 114-117, in particular). Aay et al further teaches said method comprising further administering to the subject one or more additional inhibitor selected from a group comprising an inhibitor of SOS1, SHP2, EGFR, MEK, CDK4/6, PI3Ka, or a combination thereof ([0330] and claim 120, in particular). Aay et al further teaches compounds that inhibit Kras-G12D inhibit KRAS signaling (Fig. 13, in particular). Aay et al further teaches inhibitors of Kras-G12D inhibit cell proliferation (Fig 3, in particular).
Although Aay et al does not specifically teach administering the Kras-G12D inhibitors in combination with inhibitors of SOS1, SHP2, EGFR, MEK, CDK4/6, and/or PI3Ka results in synergistic inhibition of proliferation of the cells or reduced Ras signaling output of cancer cells of the subject, the claimed method appears to be the same as the prior art, absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the method of the prior art does not possess the same material, structural and steps-like characteristics of the claimed method. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed method is different from that 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 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Further, one would have been motivated with an expectation of success to treat Kras-G12D expressing cancer cells of any cancer type disclosed by Aay et al in a subject comprising administering compounds that inhibit Kras-G12D to the subject in combination with inhibitors of SOS1, SHP2, EGFR, MEK, CDK4/6, and/or PI3Ka because Aay et al teaches methods of treating Kras-G12D expressing cancer cells in a subject comprising administering compounds that inhibit Kras-G12D to the subject in combination with inhibitors of SOS1, SHP2, EGFR, MEK, CDK4/6, and/or PI3Ka.
Claim Rejections - 35 USC § 103
Claim(s) 1-15, 21, 23, 24, 65 and 66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Aay et al (US 2022/0105185 A1; 4/7/2022) as applied to claims 1-15, 65, and 66 above, and further in view of Wang et al (Cell Death and Disease, 2018, 9(739): 1-11).
Teachings of Aay et al are discussed above.
Aay et al does not specifically teach a method wherein the subject of Aay et al that has colorectal cancer and is administered a combination of the Kras-G12D inhibitor and the PI3K inhibitor of Aay et al wherein the subject further has a PI3k (same as “PIK3CA”) genetic mutation. However, these deficiencies are made up in the teachings of Wang et al.
Wang et al teaches PI3K is one of the most mutated genes in colorectal cancer (right column on page 1, in particular). Wang et al teaches PI3K mutation induced PI3K/Akt activation contributes to colorectal cancer stem cell survival and proliferation (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the method of Aya et al wherein the subject has colorectal cancer with a PI3K mutation and is administered a combination of the Kras-G12D inhibitor and PI3K inhibitor as the additional inhibitor(s) of Aay et al because in an effort to inhibit PI3K mutation induced PI3K/Akt activation because Wang et al teaches PI3K mutation induced PI3K/Akt activation contributes to colorectal cancer stem cell survival and proliferation. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN E AEDER whose telephone number is (571)272-8787. The examiner can normally be reached M-F 9am-6pm 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, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SEAN E AEDER/ Primary Examiner, Art Unit 1642