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 .
Status of Claims
Claims 1-31 are pending in the instant application.
Information Disclosure Statement
The Information Disclosure Statements (IDS) filed 06/28/2024 and 10/14/2025 were considered by the Examiner.
Response to Restriction/Election Requirement
Applicant’s election without traverse of Group I, drawn to a method, in the reply filed on October 1st, 2025 is acknowledged.
As the elected group has been found not allowable, claims drawn to the nonelected invention are held withdrawn from further consideration. As such, claims 11-31 have been withdrawn as being embraced by a nonelected invention.
Claim Objections
Claim 2 is objected to because of the following informalities:
The pictures of the structures are unclear. Appropriate correction is required.
Claims 3 and 9 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should be in the alternative only. See MPEP § 608.01(n).
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.
Claims 1 and 9 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling a method of killing a cancer cell and treating a disorder associated with Arf1 pathway activity, does not reasonably provide enablement for killing a progenitor or a stem cell or a cancer stem cell and prevent any disorder associated with Arf1 pathway activity. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4) amount of direction provided by the inventor; (5) the level of predictability in the art; (6) the existence of working examples; (7) quantity of experimentation needed to make or use the invention based on the content of the disclosure; and (8) relative skill in the art. All of the factors have been considered with regard to these claims, with the most relevant factors discussed below:
1) The breadth of claims: The instant claims are directed to a method of killing a progenitor or a stem cell or a cancer stem cell and preventing a disorder associated with the Arf1 pathway activity. This is a very broad claim, one that is not supported by the instant specification. For instance, the claims recitation of “a progenitor cell” can read a multitude of cells in the body.
2) The nature of the invention: The nature of the invention is killing a progenitor or a stem cell or a cancer stem cell and preventing a disorder associated with the Arf1 pathway activity. Currently, there are no known agents that prevent all disorders associated with the Arf1 pathway. For instance, there is no known agent that prevents epilepsy.
3) The state of the prior art: The state of the art is very high in terms of compositions comprising a drug for killing a cancer cell and treating a disorder associated with the Arf1 pathway activity. However, there is no evidence in the prior art that the instant composition would kill a progenitor or a stem cell or a cancer stem cell or prevent a disorder associated with the Arf1 pathway from occurring.
4) The amount of direction provided by the inventor: There is nothing in the specification that would indicate that the current invention kills progenitor or a stem cell or a cancer stem cell or prevents a disorder associated with the Arf1 pathway from occurring or reoccurring. The method of killing progenitor or a stem cell or a cancer stem cell and prevention of a disorder associated with the Arf1 pathway is a very broad claim. However, there is a substantial gap between treatment and prevention. Consequently, a burdensome amount of research would be required by one of ordinary skill in the art to bridge this gap.
5) Predictability of the art: The preventing of a disorder of associated with Arf1 activity is highly unpredictable due to the numerous sources that could trigger the disorders. Further, the killing of a progenitor or a stem cell or a cancer stem cell is highly unpredictable due to the numerous types of cells encompassed by the claim language.
6) The presence or absence of working examples: Applicant has some examples of administering the composition to cancer cells in the instant specification, none of which teaches how to prevent a disorder associated with Arf1 activity or kills a progenitor or a stem cell or a cancer stem cell. Overall, applicant fails to provide examples showing that the instant method could kill a progenitor or a stem cell or a cancer stem cell or prevent a disorder associated with Arf1 activity. Therefore, the practitioner would turn to trial and error experimentations to make/use the instant compositions for preventing a disorder associated with the Arf1 pathway or kill a progenitor or a stem cell or a cancer stem cell from the specification or the prior art.
7) The quantity of experimentation: In the instant case, there is a substantial gap between treatment and prevention. Consequently, a burdensome amount of research would be required by one of ordinary skill in the art to bridge this gap. In order to utilize the composition as claimed, the skilled artisan would be presented with an unpredictable amount of experimentation. An undetermined number of experimental factors utilizing a system for preventing a disorder associated with Arf1 pathway acidity or killing a progenitor or a stem cell or a cancer stem cell would have to be resolved by the practitioner and/or the patient. The disclosure is not sufficiently discussed in the specification to provide guidance to utilize the invention as claimed.
8) The relative skill of those in the art: the skill of one of ordinary skill in the art is high, e.g. Ph.D. and M.D. level skill.
In summation, Applicant does not reasonably provide enablement for killing a progenitor or a stem cell or a cancer stem cell or preventing a disorder associated with Arf1 pathway activity.
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 1-10 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.
Regarding claim 1, the phrase "particularly" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claims 2-10 do not resolve the issue of indefiniteness and as such, are also rejected under 112(b).
Further, the claim recites “a compound related formula (I)” it is unclear to what degree a compound would need to be related to formula (I) to be embraced by the claim. This is relative terminology and there is no guidance on how much or what kind of relation is necessary to meet the claim language. Claims 3-10 do not resolve the issue of indefiniteness and as such, are also rejected under 112(b).
Also regarding claim 1, the claim language regarding the options for R1 is unclear. It is unclear if R1 can be a phenyl substituted with the substituents listed in lines 8-10 of the claim or must be unsubstituted. It is also unclear if R1 can only be phenyl or the heteroaryl rings listed in line 7 of the claim. For the purposes of examination, Examiner has interpreted the claim as that R1 can be phenyl substituted with the substituents listed in lines 8-10 of the claim along with the heteroaryl rings in line 7 of the claim. Claims 3-10 do not resolve the issue of indefiniteness and as such, are also rejected under 112(b).
Regarding claim 10, the claim recites the limitation "aberrant Arf1 pathway activity" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 3-6 and 8-9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lang et al (Journal of Experimental & Clinical Cancer Research (2017) 36:112, as cited on the IDS dated 06/28/2024).
Lang teaches the administration of Exo2 to DU145 and PC3 cells (page 4, right column, paragraph 2). Exo2 is of the following structure (Fig. 6):
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. Exo2 is embraced by instant formula (I), wherein r is 2 and R1 is phenyl substituted with OH and OCH3.
Lang further teaches that Exo2 inhibited cell migration and invasion and induced apoptosis in prostate cancer cells (page 4, right column, paragraph 2). Lang also teaches that Exo2 reduces Arf1 activation and effectively suppresses cell proliferation by blocking ERK1/2 activation. Exo2 also has other effects, inhibiting migration and invasion of PCa cells and inducing apoptosis (results).
As such, regarding claim 1, Lang teaches a method of killing a cancer cell and inducing anti-tumor response, comprising inhibiting the Arf1 pathway with a compound of instant formula (I).
Regarding claim 3, as seen above, Lang teaches the administration of Exo2 to a PCa and DU145 cells, which inhibits Arf1 pathway activity.
Regarding claim 4, PCa cells and DU145 cells are progenitor cells.
Regarding claim 5, PCa cells and DU145 cells are cancer cells.
Regarding claim 6, as seen above, Exo2 induces cell apoptosis.
Regarding claim 8, as seen above, the administration of Exo2 is carried out in vivo.
Regarding claim 9, as seen above, Exo2 is administered as a way of treating cancer.
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 (i.e., changing from AIA to pre-AIA ) 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.
Claim(s) 1-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Guetzoyan et al (Mol. BioSyst., 2010, 6, 2030–2038, as cited on the IDS dated 06/28/2024) in view Lang et al (Journal of Experimental & Clinical Cancer Research (2017) 36:112, as cited on the IDS dated 06/28/2024).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Guetzoyan teaches the administration of the following compound to HeLa cells (Table 3):
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, wherein Ar is
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. This compound is embraced by formula (I), wherein r is 2 and R1 is
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.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Guetzoyan does not explicitly teach that the administration of the above compound kills a cancer cell and inhibits the Arf1 pathway.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Lang teaches the administration of Exo2 to DU145 and PC3 cells (page 4, right column, paragraph 2). Exo2 is of the following structure (Fig. 6):
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. Exo2 is embraced by instant formula (I), wherein r is 2 and R1 is phenyl substituted with OH and OCH3.
Lang further teaches that Exo2 inhibited cell migration and invasion and induced apoptosis in prostate cancer cells (page 4, right column, paragraph 2). Lang also teaches that Exo2 reduces Arf1 activation and effectively suppresses cell proliferation by blocking ERK1/2 activation. Exo2 also has other effects, inhibiting migration and invasion of PCa cells and inducing apoptosis (results).
Further, Guetzoyan teaches that the compound of formula (I), above, shows similar morphological effects to Exo2, and it exhibited a lower toxicity profile and an excellent retention of protein synthesis after SLTx challenge.
Regarding claim 1, as Guetzoyan teaches a compound of formula (I) being administered to HeLa cells and Lang teaches that Exo2 inhibits cell migration and invasion and induced apoptosis in prostate cancer cells one of ordinary skill in the art would have a reasonable expectation of success of the compound of formula (I) being used in a method of killing a cancer cell as Guetzoyan teaches that the compound of formula (I) shows morphologically similar properties to Exo2.
Regarding claim 2, the compound taught by Guetzoyan is compound 105.
Regarding claim 3, as seen above, Lang teaches the administration of Exo2 to a PCa and DU145 cells, which inhibits Arf1 pathway activity.
Regarding claim 4, PCa cells and DU145 cells are progenitor cells.
Regarding claim 5, HeLa cells are cancer cells.
Regarding claim 6, as seen above, Exo2 induces cell apoptosis.
Regarding claim 7, one of ordinary skill in the art would have been motivated to carry out the process in vitro as the in vivo study presented promising results.
Regarding claim 8, as seen above, the administration of Exo2 and the compound of formula (I) is carried out in vivo.
Regarding claim 9, as seen above, Exo2 and the compound of formula (I) are administered as a way of treating cancer
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Grace Kuckla whose telephone number is (703)756-5610. The examiner can normally be reached Monday-Friday 7:30-5.
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/A.G.K./Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699