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
Claims 1-11 and 14-24 are pending in the application. Claims 16, 17 and 21-23 are rejected. Claims 1, 2, 6, 10, 11, 14-16 and 18 are objected to. Claims 3-5, 7-9, 19, 20 and 24 are allowed.
Priority
This application is a 35 U.S.C. § 371 National Stage Filing of International Application No. PCT/CN2022/103056, filed on June 30, 2022, which claims priority to Chinese Application No. CN202210675157.9, filed on June 15, 2022, which claims priority to Chinese Application No. CN202210042057.2, filed on January 14, 2022, which claims priority to Chinese Application No. CN202111398357.6, filed on November 19, 2021, which claims priority to Chinese Application No. CN202111062878.4, filed on September 10, 2021, which claims priority to Chinese Application No. CN202110873254.4, filed on July 30, 2021, which claims priority to Chinese Application No. CN202110752493.4, filed on July 2, 2021.
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. § 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statement(s) (IDS) filed on April 5, 2024, March 31, 2025, August 29, 2025 and January 5, 2026 are in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the Examiner has considered the IDS documents and signed copies of the 1449 forms are attached.
Claim Objections
Claim 1, 2, 6, 10, 11, 14-16 and 18 are objected to because of the following informalities:
Claim 1 should be amended to replace “one or more than one R9” with -one or more R9- for sake of clarity. See R1 variable definition on page 4.
Claim 1 should be further amended to replace “one or more than one Rc” with -one or more Rc- for sake of clarity. See RA variable definition on page 5.
Claim 1 should be further amended to replace “one or more than one substituent” with -one or more substituent- for sake of clarity. See “RA and RB” variable definition on page 5.
Claim 1 should be further amended to replace “one or more than one substituent” with -one or more substituent- for sake of clarity. See Rc variable definition on page 6.
Claim 1 should be further amended to include the word -and- before the expression “t is 0, 1, 2 or 3” for sake of proper Markush language.
Claim 2 should be amended to replace “Z is C; Z1 is CR8; Z2 is N; or Z is C; Z1 is CR8; Z2 is CR8; or, each R8 is independently hydrogen or halogen” with -Z is C; Z1 is CR8; Z2 is CR8 or N, wherein each R8 is independently hydrogen or halogen- for sake of clarity.
Claim 6 should be amended to replace “substituted at any position by 1 to 5 fluorine, deuterium, and methyl” with -substituted at any position by 1 to 5 fluorine, deuterium, and/or methyl- for sake of clarity as this appears to be Applicant’s intent.
Claim 10 should be amended to include the word -and- before the expression “R3 is H” for sake of proper Markush language.
Claim 11 should be amended to replace “The compound of formula (I)” with -The compound of formula (II)- for sake of consistency as this appears to be Applicant’s intent.
Claim 14 should be amended to replace the expression “has any one of the following structures” with -which is any one of the following structures- for sake of clarity.
Claims 14 and 15 should be amended to cancel “,or a pharmaceutically acceptable salt” at the end of each claim for sake of clarity.
Claim 15 should be amended to replace the expression “has any one of the following structures” with -which is any one of the following structures- for sake of clarity.
Claim 16 should be amended to replace the expression “has any one of the following structures” with -which is any one of the following structures- for sake of clarity.
Claim 18 should be amended to include the word “or” before the last recited compound structure for sake of proper Markush language.
Claim 18 should be amended to recite “a pharmaceutically acceptable salt thereof” for sake of clarity and consistency. See last line of claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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.
Claim 21 is 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 a method of treating cancer comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) wherein said cancer is as described in paragraph [0323] (reproduced below) of the instant specification, does not reasonably provide enablement for treating “cancer” which could reasonably be interpreted as any and all cancer.
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The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with this claim.
As a general rule, enablement must be commensurate in scope with the claim language. The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). See MPEP § 2164.08. That some experimentation may be required is not fatal; the issue is whether the amount of experimentation required is “undue.” In re Vaeck, 947 F.2d 488, 495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991).
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
The above factors, regarding the present invention, are summarized as follows:
Breadth of the Claim – The breadth of the claim is drawn to a method of treating or alleviating cancer in a subject in need thereof comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I) or a stereoisomer, stable deuterated derivative, or pharmaceutically acceptable salt thereof. Accordingly, the claim is drawn to treating a broad scope of cancers.
Nature of the Invention – The nature of the invention pertains to a method of treating or alleviating cancer with “a compound that irreversibly inhibits KRAS G12D activity.” See e.g., paragraph [0002] of the instant specification.
State of the Prior Art and Predictability in the Art – Even in view of the seemingly high level of skill in the art, there is no absolute predictability when determining the physiological effects of a compound of formula (I) against any and all cancers. It is well established that “the scope of enablement [] varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Lipinski et al. (Trends in Cancer, 2016, 49-63) even teach “[g]enomic aberrations differ between cancers of the same histological type, to the extent that no two tumors are thought to show an identical somatic genetic aberration profile.” See e.g., page 49. Therefore, a skilled artisan would reasonably expect the efficacy of treatment methods to vary when considering the diverse causes and symptoms associated with any and all cancers.
Relative Skill of Those in the Art – The artisan making and using applicant’s pharmaceutical compound would be a synthetic chemist and/or a health practitioner, possessing a commensurate degree level and/or skill in the art, as well as several years of professional experience. The level of skill in the art is high; however, due to the unpredictability in the pharmaceutical art and the wide scope of cancers, it is difficult to assess the potential pharmacological activity of a compound of formula (I) against any and all cancers.
Amount of Direction/Guidance Provided and Existence/Absence of Working Examples – The specification provides in vitro data regarding the inhibitory effect of the claimed compound of formula (I) on KRAS G12D with respect to human gastric cancer cells. See e.g., paragraph [0579]. The specification also provides in vivo data regarding the instantly claimed compound of formula (I) with respect to GP2D human colon cancer cells in a mice model. See e.g., paragraph [0585]. The disclosure also provides written support for treating various cancer types. See e.g., paragraph [0323]. However, the disclosure does not provide support for treating any and all cancers (i.e., the scope of instant claim 21). There is no actual evidence of the effectiveness of the claimed composition in treating the full scope of cancers claimed. Ex parte Stevens, 16 USPQ2d 1379.Quantity of Experimentation Necessary – The quantity of experimentation needed to use the invention based on the content of the disclosure is undue. One of skill in the art would need to determine which specific cancer not embraced by the instant disclosure would benefit from the pharmacological activities of a compound of formula (I) by administering said compound to a patient. Using the full scope of the instant claim is made further burdensome when one considers that even human testing “limited to one compound and two types of cancer” was not “commensurate with the broad scope of utility asserted and claimed.” In re Buting, 57 CCPA 777, 418 F.2d 540, 163 USPQ 689. The claimed invention would require a person having ordinary skill to invest an indefinite amount of experimentation clearly beyond what can be considered as routine.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). In view of the Wands factors and In re Fisher (CCPA 1970) discussed above, a person of skill in the art would have to engage in undue experimentation to test which cancers can be treated by a compound of formula (I), with no assurance of success. It is suggested Applicant further limit the “cancer” as recited in claim 21 to overcome this issue of lack of enablement (e.g., incorporate limitations regarding specific cancer type(s) and/or KRAS G12D association into claim).
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.
Claims 16, 17, 22 and 23 are rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. § 112, the applicant), regards as the invention.
Claim 16 recites the limitation “the HPLC analysis method” and is rejected as indefinite. There is insufficient antecedent basis for this limitation either in claim 16 or in parent claim 1. It is suggested that Applicant cancel the entire wherein clause from claim 16 as recited on page 25. In addition, for each individual species of a compound of formula (I) recited in claim 16, Applicant provides two variants- labeled atropisomer 1 and atropisomer 2- that are distinguished by “HPLC retention time” as shown below.
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However, it is unclear how information regarding “HPLC retention time” affects the scope of claim 16 with respect to each recited structure. To overcome this issue of indefiniteness, Applicant should cancel all information directed towards the “HPLC retention time”- including the labeling of structures as atropisomer 1 or 2- and also amend the claim to correct for the double inclusion of structures.
In addition, claim 16 contains the trademark/trade name “Xtimate.” Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe XTIMATE™ and, accordingly, the identification/description is indefinite.
Claim 17 recites the following limitation and is rejected as indefinite:
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The term “above” appears to be in reference to subject matter recited in claims 1-17. However, it is unclear whether Applicant intended variables
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of claim 17 to encompass the broadest variable definitions as recited in parent claim 1 or to be limited to a narrower list of alternatives as recited in claims dependent therefrom. Regarding variables
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of claim 17, parent claim 1 provides the following broadest variable definitions:
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However, there are multiple instances in the “above” claims where these same variables are defined by a narrower list of alternatives. For instance:
- At least claim 2 limits variable “Z1” to “CR8.”
- At least claim 10 limits variable “q” to “1.”
- At least claim 7 limits variable “R1” as follows:
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- At least claim 3 limits variable “RA” as follows:
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Therefore, based on the term “above” as recited in claim 17, it is unclear what Applicant intended the scope of claim 17 to be with respect to variables
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.
Claim 22 recites the expression “preferably one or more than one of” and “(preferably small cell lung cancer or non-small cell lung cancer)” and is rejected as indefinite. It is unclear whether Applicant intended these expressions to further limit “the cancer” as recited in the claim. It is suggested that Applicant cancel both of these expressions to overcome this issue of indefiniteness.
Claims 22 and 23 both recite “and colorectal cancer” and are rejected as indefinite. It is unclear how “the cancer” (i.e., singular) can be defined as being multiple cancer types simultaneously. It is suggested that Applicant replace the word “and” with the word -or- to overcome this issue of indefiniteness.
Allowable Subject Matter
Claims 3-5, 7-9, 19, 20 and 24 are allowed.
Conclusion
Claims 1-11 and 14-24 are pending in the application. Claims 16, 17 and 21-23 are rejected. Claims 1, 2, 6, 10, 11, 14-16 and 18 are objected to. Claims 3-5, 7-9, 19, 20 and 24 are allowed.
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/D.M.S./Examiner, Art Unit 1626
/REBECCA L ANDERSON/Primary Examiner, Art Unit 1626