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 the Claims
Claims 2-5, 8-10, 13, 15-16, 18-22, and 24-28 are cancelled. Claims 1, 6, 7, 11, 12, 14, 17, 23 and 29-37 are pending. Claims 23 and 29-36 are withdrawn. Claims 1, 6, 7, 11, 12, 14, 17, and 37 are under examination.
Priority
This application is a 371 of PCT/US2022/034522, filed on 6/22/2022. The application is claiming priority to U.S provisional Application No. 63/213,990 filed 6/23/2021.
Objections and Rejections Withdrawn
The objections over claim 2 are withdrawn per cancellation of claim 2.
The objection over claim 14 for abbreviations is withdrawn per applicant’s amendment to the claim to provide the unabbreviated terms.
The objection over claim 17 is withdrawn per applicant’s amendment to the claim.
The rejection under USC 101 is withdrawn per applicant’s amendment to include a compound structure in claim 1 that is not natural (see applicant’s amendments and arguments).
The rejection under USC 112(a) for “one or more metabolites, derivatives, prodrugs or pharmaceutical salts thereof” is withdrawn per applicant’s amendment to claim 1 to include a compound structure that is described in applicant’s disclosure.
The rejection under USC 112(a) for written description of vaccine, immunotherapy or ICI inhibitor in claim 37 is withdrawn as applicant defined the compound for the composition of claim 1 and is able to add active agents (vaccines, immunotherapies) along with the compound introduced in claim 1. Applicant may produce kits of its compound in the composition of formula I with various vaccines or cancer immunotherapies as being other therapeutic agents.
The rejection under USC 112(a) for scope of enablement is withdrawn per applicant’s amendment and arguments.
The rejection under USC 112(b) for indefiniteness of claim 1 and dependent claims of claim 1 for indefiniteness of derivatives and prodrugs is withdrawn per applicant’s amendment to claim 1. Note that claim 14 was and is still rejected for containing “derivatives” in the claim.
The rejection under USC 112(b) for indefiniteness of claim 1 and dependent claims of claim 1 for “one or more metabolites; derivatives, prodrugs, or pharmaceutical salts thereof” is withdrawn per applicant’s amendment to claim 1.
The rejection under USC 112(b) for indefiniteness of claim 2 and its dependent claims is withdrawn per applicant’s cancellation of claim 2 rendering the rejection moot.
The rejection under USC 112(b) for indefiniteness of claims 6 and 7 for whether the compound is necessary or still optional is withdrawn per applicant’s amendment to claim 1.
The rejection under USC 112(b) for indefiniteness of claim 7 for "for example (e.g.)" is withdrawn as applicant has deleted this recitation.
The rejection under USC 112(b) for indefiniteness of claim 7 for a possibly incomplete limitation is withdrawn as applicant has deleted this recitation.
The rejection under USC 112(b) for indefiniteness of claim 7 for metabolite is withdrawn due to applicant’s deletion of this word from the claim.
The rejection under USC 112(b) for indefiniteness of claim 11 for “the biodegradable agent” is withdrawn per applicant’s deletion of this agent from the claim.
The rejection under USC 112(b) for claim 14 for “DOPE@liposome” is withdrawn per applicant’s deletion of this recitation from the claim.
The rejection under USC 112(b) for claim 17 for lack of clarity if “and” or “or” connects the items of the claim is withdrawn per applicant’s amendment to add an “and”.
The rejection under USC 112(b) for claim 37 for use of e.g. is withdrawn per applicant’s deletion of this recitation.
The rejection under USC 112(d) for claims 6 and 17 based on the where compounds would allow a hydrogen at the R5 position is withdrawn as applicant has amended claim 1 to have the compound have hydrogen at the R2 position.
The rejection under USC 102 over Tantawy is withdrawn per applicant’s amendment to claim 1.
The rejection under USC 102 over Doherty is withdrawn per applicant’s amendment to claim 1.
The rejection under USC 102 over Li et al is withdrawn per applicant’s amendment to claim 1.
The rejection under USC 102 over He et al is withdrawn per applicant’s amendment to claim 1.
The rejection under double patenting over 17/762,980 is withdrawn per applicant’s amendment to claim 1.
As these objections and rejections are withdrawn, applicant’s arguments toward these rejections are moot.
Maintained Objection
Claim Objections
Claim 6 is objected to for “selected from…..and….” where the appropriate language would be “selected from….or….” for this group of optional items. Alternatively, applicant can use “selected from the group consisting of….. and….” Format.
Appropriate correction is required.
Response to Arguments-
Applicant acknowledges this objection on page 12 of the arguments filed on 6/1/2026, but does not indicate doing a correction or a reason why they felt a correction was not needed. Therefore, this objection is maintained.
Maintained Rejections under USC 112(a)
Claim Rejections - 35 USC § 112 (a) – Written Description
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 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 14 lacks adequate written description as it includes the use of the phrase “any nanostructures, microstructures, or their derivatives formed using layer by layer processes, self-assembly processes, or polyelectrolytes” for nanoparticles of this group. There is no description of all the possible layer by layer processes or the nanostructures, microstructures or their derivatives that could be produced. Note that nanostructure and microstructure only indicate a size limitation, but not any description of a type of structure or what other items would be incorporated into that structure with a layer by layer process or a self-assembly process. There is not sufficient description of the layers that could be produced or the various derivations that might be made. Applicant does have more defined structures and species in claim 14 such as “carbon nanohorns”, “nanorods”, “cellulose nanoparticles”, and “iron nanoparticles” as well as more defined derivatives such as “4arm-PEG-polyhistidine-metal hydrogels” and “sHDL-polyhistidine”, where there is adequate description for these more particular items.
Claim 14 lacks adequate written description as it includes the limitation of “modified micelle” without providing adequate description of the modifications that can be made or a definite of what modified micelle would mean. Modified implies some type of modification which may be of various structures, groups and the result of different processes. Applicant may simply say “a micelle” as this would encompass various micelles.
Response to Arguments over the Rejections under USC 112(a) over claim 14
In regards to the rejection regarding “any nanostructures, microstructures, or their derivatives formed using layer by layer processes, self-assembly processes, or polyelectrolytes”, applicant indicates these were limited to what applicant has support for (see arguments filed on 6/1/2026 on page 16), but they did not remove “or their derivatives” or amend this limitation in another way. Thus, this rejection is maintained. Applicant could simply say “nanostructures or microstructures formed using layer by layer processes”
Applicant did not address or argue the rejection regarding “modified micelles”. It is maintained that the modifier of “modified” provides for a number of derivations of micelles where applicant does not have adequate description. Applicant did not delete “modified” in the claim. Therefore, this rejection is maintained.
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, 6, 7, 11, 12, 14, 17, and 37 are or remain 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.
Maintained Rejections – Modified As Necessitated by Amendment As Applicable
Claim 14 is indefinite for “derivatives” as the specification does not provide for a reasonable definition or enough adequate species to define structures for “derivatives” in claim 14. In claim 14, there is a recitation of derivatives in regards to various nanoparticle types preceding it in the claim. Again, it is unclear what structural derivations are being provided for the metes and bounds of this limitation and if they are in regards to the compounds of the nanoparticles or the nanoparticles themselves. For the purpose of compact prosecution, if the prior art provides a compound that may be construed as a derivative or prodrug, it will read on the claim and if the prior art teaches a nanoparticle that can be construed as a derivative of nanoparticle or one of the compounds thereof, it will read on the claim.
Claim 14 is indefinite for the recitations of microparticle or micro- particle or microsphere in the claim when the group is meant to contain nanoparticles. It is indefinite if applicant means to redefine nanoparticles to also include types of microparticles (e.g. particles of a different size range) or if these are meant to be excluded from the group based on the introduction of “nanoparticle is selected from the group consisting of…”. For the purpose of compact prosecution, the examiner will consider the claim for items it contains.
Claim 14 is indefinite for having multiple recitations of “and” and “or” within the Markush group. This makes it difficult to determine if the Markush group ends at the first recitation of “and multi-walled carbon nanotubules” in line 3 or at “or polyelectrolytes” or at “and polymer micro- and nano-spheres” or any of the other later recitations of “and” or “or”. A Markush group is in the format of “selected from the group consisting of…… and…..” where “and” precedes the last item of the group.
Claim 14 is indefinite for “boron/nitrate” as it is unclear if it is “boron and nitrate”, “boron or nitrate” or “boron and/or nitrate” due to the use of the “/”. The examiner will read as and/or for compact prosecution.
Claim 37 is indefinite for the phrase “one or more of a vaccine…and a cancer immunotherapy” as it is unclear if applicant wants to choose one or more vaccines and then additionally have a cancer immunotherapy or if applicant wants to choose from either vaccines, cancer immunotherapy or both vaccines and cancer immunotherapies. For the purpose of compact prosecution, the examiner will read the claim as it may be one of the options or both options.
Response to Arguments-
Applicant argues that claims 14 and 37 are amended to address the rejections under USC 112(b) over claims 14 and 37. Although one of the rejections for each claim was addressed via amendment, the above remaining rejections had not been amended to repair. Arguments were not provided if they did not agree. Therefore, these rejections are maintained.
New USC 112(b) rejections – As Necessitated by Amendment
Claims 1 and 17 recites the limitation "R3", “R4” and “R5” in the claim without providing a compound or compound group that has an R3, R4 and R5 variable. There is insufficient antecedent basis for this limitation in the claim. The only R groups listed in structures or groups of the compound of formula I are R1, R2, R6, R7, R8, and R9. Either a compound is missing from claim 1 or R3, R4 and R5 should be deleted from the claims as not having basis in the compounds of the claims.
Claims 6, 7, 11, 12, 14, and 37 are rejected for being dependent on indefinite claims.
Claims 6 recites the limitation of the first six listed compounds in the claim without providing compound structure that give them a basis from claim 1, on which it depends. There is insufficient antecedent basis for this limitation in the claim. The structure recited in claim 1 does not provide antecedent basis for the compounds with no five membered rings and also does not provide support for the salt compound with HCl since there are no “or pharmaceutically acceptable salts thereof” in claim 1 after amendment.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
New Rejections – As Necessitated by Amendments
Claim 6 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 6 provides six member ring structures that would not fit the compound of formula I based on the structure for the prodrug compound that was imported into claim 1 by applicant. Thus, compounds in claim 6 do not limit the compound structure in claim 1 as they extend to compound where the ring structure is different. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 14 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 14 provides nanoparticles that would include other items such as lipoproteins, carbon nanotubes, gold, etc. while claim 11, on which it depends, says that the prodrug compound is a microparticle or nanoparticle, which would close the microparticle or nanoparticle to be the prodrug compound by itself. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Applicant could amend claim 11 to say “wherein the prodrug compound is in a microparticle or nanoparticle” so that the prodrug compound is not necessarily all of the microparticle or nanoparticle.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Maintained Rejections – Modified As Necessitated by Amendment
Claims 1, 6, 7, 11, 14, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Doherty US6008372A.
Example 6 teaches pi-N-methyl histidine methyl ester dihydrochloride.
Some of Doherty’s teachings are provided above including pi-N-methyl histidine methyl ester dihydrochloride. Doherty teaches
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(column 65). R can be hydrogen or alkyl, R4 groups may be alkyl (column 7). R6 is noted as hydrogen (column 10). Y is C=O Doherty teaches substituted histidine of the compound of formula I (abstract) and that they are effective for cancer treatment (abstract). Doherty teaches various carriers such as powders and dispersible granules along with various ingredients (bottom of column 66). Doherty teaches powders (column 67). Doherty teaches inhalation and injections as forms of delivery (column 66). Powders/particles for injection and inhalation would include powder particles in the micron to nanometer size range. It is noted that example 5 provides for histidine ethyl ester dihydrochloride. Applicant repaired claim 7 and the missing limitation was “a biodegradable agent”. Doherty provides for suitable carriers such as starch, sugar and methylcellulose (column 67, lines 4-15) where these would be recognized as biodegradable components.
One of ordinary skill in the at before the time of filing would have the teachings from Doherty to modify histidine with pi-N-methyl group to provide for alkyl esters as Doherty provides compounds with such groups and that such histidine derivatives provide as useful cancer treatments. Therefore, there was a reasonable expectation of success in formulating other compounds of applicant’s claims by the teachings of Doherty motivated to make new substituted histidine compounds to treat cancer and other diseases. It is also obvious to modify known compounds with short alkyl groups with the reasonable expectation of similar activities such as anticancer activity (see MPEP 2144.09 – close structural similarity between chemical compounds).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Doherty US6008372A and Violante US4997454A.
Doherty teaches the claims as discussed above.
Doherty does not teach particle sizes in claim 12.
Violante teaches making uniformly sized particles for solid compounds and desired suspending vehicles (abstract). Violante teaches mean particle diameters of 0.01 to 0.1 microns, 0.1 to 4 microns or about 1 to about 10 microns (claims 10-12 of Violante). Violante teaches the particles for injection to the patient (claim 16 of Violante). Violante teaches an anticancer compound (column 4).
One of ordinary skill in the art before the time of filing would have produced particles for injections based on teachings of Violante for the compounds provided in Doherty to provide better injectable forms for delivery to patients. Thus, there was a reasonable expectation of success in combining the teachings of the references to produce injectable formulations of cancer drugs with particle sizes of applicant’s claims.
Response to Applicant’s Arguments over the Rejection under USC 103
Applicant argues that Doherty does not teach a compound of applicant’s claims, however, Doherty teaches a genus structure with variable groups that are pointed out to allow groups (such as alkyl, hydrogen) at the same positions as in applicant’s claimed formula. It was also noted that these compounds in Doherty are structurally similar to claimed compounds and recognized by Doherty to be functionally useful to treat cancers. Due to the broad genus of possible compounds due to the R1, R2 groups and allowed substitution to R1 in applicant’s claims, there is a reasonable expectation of success in producing compounds of applicant’s claims and obvious variants by teachings of the genus and variable groups in Doherty and having those compounds also functional in treating cancer. Additionally, note that Doherty has a teaching of pi-N-methyl histidine methyl ester dihydrochloride, which is very close structurally to applicant’s methyl Np-methyl-L-histidinate hydrochloride (compound found in examples and claim 6 of applicant) with the only difference being an extra HCl in Doherty.
Applicant argues that the compounds of its claims act in a different mechanism than Doherty’s compounds. Applicant indicates that Doherty’s compounds are farnesyltransferase inhibitors that directly suppress cancer cell proliferation while the applicant’s claimed compounds do not directly kill cancer cells but instead potentiate anti-tumor immune responses through central memory T cell induction when combined with immune checkpoint blockade/inhibition. Doherty’s compounds are structurally similar that they would be expected to have similar effects. Additionally, applicant does not show that its compounds cannot also inhibit farnesyltransferases. The combination of applicant’s compound with another agent (immune checkpoint blocker) for an effect is also a result toward that combination. None of the claims provide immune checkpoint inhibitors specifically. Applicant should also consider the data they have toward particular combinations of their more particular compounds of formula I with immune checkpoint inhibitors, more particularly alpha-PD-1 immune checkpoint blocker (see example I and example II).
Applicant argues that there was no motivation to combine these unrelated fields, which appears to refer to improving cancer immunotherapy vs cancer treatment with farnesyltransferase inhibitors. The motivations and rationale of the prior art do not have to be the same as those intended by the applicant (MPEP 2144 IV). “The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn”. Additionally, “In In re Lintner, the claimed invention was a laundry composition consisting essentially of a dispersant, cationic fabric softener, sugar, sequestering phosphate, and brightener in specified proportions. The claims were rejected over the combination of a primary reference which taught all the claim limitations except for the presence of sugar, and secondary references which taught the addition of sugar as a filler or weighting agent in compositions containing cationic fabric softeners. Appellant argued that in the claimed invention, the sugar is responsible for the compatibility of the cationic softener with the other detergent components. The court sustained the rejection, stating “The fact that appellant uses sugar for a different purpose does not alter the conclusion that its use in a prior art composition would be [sic, would have been] prima facie obvious from the purpose disclosed in the references.” 173 USPQ at 562”. Thus, both Doherty and the applicant’s claimed invention are pertinent to cancer treatment regardless if they are being used for different purposes/mechanisms.
As the rejection over Doherty is being maintained, the rejection over Doherty and Violante in regards to claim 12 is also being maintained.
New Rejection With Previously Cited References – As Necessitated by Amendment to Claim 1 to Incorporate A Genus Structure into Claim 1 (Changes Scope of Dependent Claim 37)
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over Doherty US6008372A and He et al (Cancer Biol Ther, 2017, volume 18, pages 94-100, previously cited).
Doherty teaches the claims as discussed above. Doherty teaches use for cancer treatment.
Doherty does not teach combining its agent with an immunotherapy or vaccine.
He teaches arginine supplementation with PD-L1 antibody boosts the immune response against osteosarcoma in mice (title and abstract and results). Thus, this anticipates a kit of parts having both reagents to carry out the treatment.
As both Doherty and He provide for treatments that can treat cancers, one of ordinary skill in the art before the time of filing would have sought to combine such treatments to improve cancer (e.g. osteosarcoma) treatment in a subject (see MPEP 2144.06). Thus, there was a reasonable expectation of success in combining teachings of the references to improve cancer treatment for a patient by formulating kits/products with the combination of therapeutic compounds for cancer.
Conclusions
No claim is found allowable.
Applicant's amendment necessitated the new 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 MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
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, Brian-Yong Kwon can be reached at (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613
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