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 3-5, 8-10, 13, 15-16, 18-22, and 24-28 are cancelled. Claims 1, 2, 6, 7, 11, 12, 14, 17, 23 and 29-37 are pending. Claims 23 and 29-36 are withdrawn. Claims 1, 2, 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.
Election/Restriction
Applicant’s election without traverse of group I, claims 1-2, 6-7, 11-12, 14, 17 and 37, and species a) 4-(ethoxycarbonyl)-1,2-phenylene bis (2,2-dimethylpropanoate) and b) anti-PD1 antibody, in the reply filed on 1/30/2026 is acknowledged. Claims 23 and 29-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/30/2026. The species election is also treated without traverse as there was no traversal with the election.
The elected species of a) 4-(ethoxycarbonyl)-1,2-phenylene bis (2,2-dimethylpropanoate) was not found in the prior art, so the examiner moved to next species of metabolites that were taught in the prior art.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/4/2025 has been considered by the examiner.
Claim Objections
Claim 2 is objected to for AICAR without spelling it out as “5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside” with its first recitation.
Claim 2 is objected to for missing an “or” between “cycloalkyl, “ and “cycloheteroaryl” in the definition of R1.
Claim 2 is objected to for different recitations of “selected from….and…” where it is more appropriately “selected from….or…” for these groups of options for R2, R3, R4 and R5. If applicant used “selected from the group consisting of ….and…” as they did in definitions of R6 and R7 and R8 and R9, then use of “and” is appropriate.
Claim 2 is objected to for a misspelling of hydroen which should be hydrogen in the definition of R6 and R7.
Claim 6 is objected to for “selected from…..and….” where the appropriate language would be “selected from….or….” for this group of optional items.
Claim 14 recites the abbreviations “sHDL”, “PLGA”, “PEG” and “DOPE” without spelling them out for the first time in the claim. sHDL is synthetic high-density lipoprotein, PLGA is poly(lactic-co-glycolic acid), PEG is polyethylene glycol, and DOPE is 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine.
Claim 17 is objected to for missing an “or” between the options for the R3 group.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 2, 6, 7, 11, 12, 14, 17 and 37 are rejected under 35 U.S.C. 101 because the claimed invention is directed to products of nature without significantly more. The claim(s) recite(s) a composition comprising metabolites, naturally occurring metabolites, and derivatives (which could include natural derivatives). This judicial exception is not integrated into a practical application because metabolites occur naturally in the cell (e.g. of an animal or plant) and the cell can modify these in different ways. Tantawy et al (PharmaNutrition, 2019, volume 8, pages 1-5) notes that amino acids including arginine, histidine and tryptophanare able to enhance immunity via increasing antibody production from T-cells (abstract and Conclusion). Thus, natural metabolites exist that can enhance T-cells (immune cells of the body) to benefit the subject. The composition may be the cell or animal/plant body itself. Further, protocatechuic acid methyl ester (R3 and R4 being H and R5 being methyl) reads on a compound of claim 2, which is a natural derivative of the natural compound protocatechuic acid (R3, R4 and R5 being H) found in plants/herbs (see Ameeramja et al (Food and Chemical Toxicology, 2018, volume 118, pages 235-244, Introduction on page 236). This natural form reads on the structure of formula II as presented in applicant’s claim 2. Claim 7 appears incomplete, however, metabolites in the body can be carried in natural vesicles or bind to other biomolecules of the body. Claim 11 only indicates the interacting item has to be biodegradable and a microparticle or nanoparticle. Vesicles, cells or other interacting molecules of the body would be on the micro or nano-scale. Claim 14 does provides some nanoparticles that are not products of nature (e.g. biodegradable PLGA micro- and nano-spheres, 4arm PEG-polyhistidine-metal hydrogels), but also encompasses microparticles, liposomes and modified micelles (does not indicate the modification is not natural). Additionally, items like nanotubes carbon nanoparticles, and nanorods can be formed in nature (e.g. volcanic activity, forest fires, some biological processes). Claim 37 provides for addition of vaccine or cancer immunotherapy in a kit. Natural immune cells and antibodies can serve as cancer immunotherapy and antigens are often natural proteins/peptides. The kit may house or separate the naturally occurring items, but does not change their natural structures or functions. The genre of both claims 1 and 37, which depends on claim 1, are very broad to cover a variety of activities where not all combinations would be considered significantly more than what occurs naturally. Claims 6 and 17 further define the prodrug structures, but does not provide that this is indeed included in the composition, and thus, remain optional by way of claim 2. Applicant may include these limitations particularly the prodrug (non-naturally occurring forms) with structural limitations as non-optional limitations into claim 1 to overcome this rejection. For example, applicant could import compounds as provided in claim 6.
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.
Claims 1, 2, 6, 7, 11, 12, 14, 17 and 37 are 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 1, 2, 6, 7, 11, 12, 14, 17 and 37 lacks adequate written description as they have dependence to claims 1 or 2, where claim 1 provides for “one or more metabolites, derivatives, prodrugs or pharmaceutical salts thereof” and claim 2 provides for a naturally occurring metabolite, which only defines the metabolite based on being of nature. Metabolites are various compounds in or taken into the body that are metabolized within the body, derivatives are any compound or metabolite that would be derived in some way with additional groups or various changes to structure with each having different functional significance, and prodrugs are compounds modified for release of the active component in the body, which include various addition groups and modes of release. There is no description of every possible metabolite of synthetic or natural compounds even those of naturally occurring compounds that are within or taken in (e.g. natural foods) to the body to be metabolized. There is no description of every type of derivative (e.g. compounds with various derivative groups with different functional consequences) and how to make each species or subgroup. There is no description of all prodrugs and how to make all of them as each would have different structure and mode of releasing the active component. Applicant does not provide an adequate number of species that would describe those entire genre of metabolites, prodrugs or derivatives. It is appreciated that applicant does provide some compound species (e.g. as listed in the Markush group of claim 2 and as listed in figure 1) as well as prodrug compound structures in claims 2 and 6. These same species and structures are provided on pages 2-3 and 15-16 with examples of applicant’s specification. Although the Applicant might consider claims with those particular compound species and compound structures that have adequate description from the originally filed disclosure, there is not adequate description for all of metabolites (including natural ones), derivatives and prodrugs. A portion of claim 2 is noted to have particular species and formulae, but still includes the option of naturally occurring metabolites. Claims 6 and 17 provide for limitations to the option of the prodrug of formula I or formula II, but do not carry a statement to whether these are included in the composition. Thus, claims 6 and 17 are only limitations to the option which has the other option of naturally occurring metabolites.
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.
Claim 37 lacks adequate written description for vaccine, cancer immunotherapy and ICI inhibitors as these encompass many various protein and nucleic acid structures that would involve different amino acid or nucleic acid sequences and modes of targeting cancer cells or altering the immune system. ICI inhibitors (under the group of cancer immunotherapy) is only defined by function to inhibit ICI, but does not carry a structural limitation itself. There are particular ICI inhibitors listed in withdrawn claim 31 including nivolumab and AMP224, which are defined by structure to carry out their functions. Applicant may amend the claim to include such species defined by both structure and function such as nivolumab and AMP224. Applicant is reminded not to add limitations to trademarks or tradenames when providing such species as this brings issues under USC 112(b).
Claim Rejections - 35 USC § 112 (a) – Scope of Enablement
Claims 1, 2, 6, 7, 11, 12, 14, 17 and 37 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 certain species and structurally defined formulae or subgroups for metabolites, natural metabolites, derivatives thereof, derivatives, prodrugs thereof, vaccines, cancer immunotherapy and ICI inhibitor, does not reasonably provide enablement for the full scope of metabolites, natural metabolites, derivatives thereof, derivatives, prodrugs thereof, vaccines, cancer immunotherapy and ICI inhibitors (defined only by function against ICI). 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 these claims.
Wankhede et al (Journal of Advanced Scientific Research, 2025, https://doi.org/10.55218/JASR.2025160601, pages 1-20) teaches challenges and strategies in prodrug design and that “The future trajectory of prodrug research necessitates a confluence of interdisciplinary expertise, integrating computational modelling, advanced bioconjugation techniques, and sustainable synthetic methodologies” (abstract). Page 4-5 of Wankhede teaches that there are challenges in prodrug design including protecting group strategies, linkage chemistry, chemical stability, bioactivation mechanisms, and enzymatic activation. Page 6 of Wankhede notes that there are structural design challenges as well including with peptide prodrugs and nucleoside prodrugs (pages 6 and 8). Wankhede concludes with “Despite their transformative potential, the development of prodrugs remains inherently complex, necessitating rigorous consideration of chemical stability, enzymatic activation kinetics, and formulation challenges” (conclusion). Alexander et al (BioProcess International, Sept 2023, https://www.bioprocessintl.com/emerging-therapeutics-manufacturing/manufacturing-challenges-of-therapeutic-antibody-drug-conjugates)) teaches the challenges in therapeutic antibody-drug conjugates (title and abstract). Alexander sees the challenges with providing monoclonal antibodies for particular functions, especially those involved in antibody drug conjugates, and that targets must be selected carefully. Alexander provides for considerations in targeting of antibodies, linkers, and manufacturing challenges with the complexity involved. Alexander sees that future directions include new technologies and improved technologies. In addition, Jayawardena et al (TrAC Trends in Analytical Chemistry, 2025, volume 183, pages 1-10) teaches many challenges in isolating specialized metabolites (section 2.1). Jayawardena also notes that “Advances in extraction, isolation, and analytical methods, coupled with multi-omics and bioengineering approaches, are rapidly enhancing our understanding and utilization of MSMs. However, sustainable bioprospecting and ethical benefit-sharing remain critical to prevent ecological impacts and ensure fair practices.” (conclusion). Thus, making new types of molecules such as prodrugs and other conjugates presents a challenge to those of skill in the art. The art recognizes the challenges and need for understanding in isolating certain metabolites as well as synthesizing new compounds and antibodies.
Applicant’s specification provides for species of known metabolites as well as certain prodrugs that they have appeared to design with compound structures. Such species and chemical formulae appear in applicant claims 2 and 6. Beyond these, applicant has not shown how to synthesize or produce its own antibodies, immunotherapies, how to identify and isolate new metabolites and how to make other prodrugs or derivatives of compounds.
One of skill in the art would be a scientist involved in design and synthesis of drugs and biologicals.
As the art recognizes the inherent difficulty of drug and antibody design and the specification provides limited guidance to the particular species or subgenre of compounds, vaccines, antibodies and immunotherapies it provides, there would be an undue burden on one of skill in the art to make and check utility of such new compounds, vaccines, antibodies and immunotherapies considering the broad genre provided in the applicant’s claims for these molecules. Thus, there is enablement for the species of metabolite compounds and other molecules applicant provides as well as some of the particular subgenre based on prodrug structures presented by applicant, however there is not enablement for other metabolites, compounds and molecules outside what the specification provides, particularly those being defined by functional consequence rather than there structure.
Please, note MPEP 2164.01 “In Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Supreme Court, held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). The Supreme Court concluded that the patents at issue failed to adequately enable the full scope of the genus of antibodies that performed the function of binding to specific amino acid residues on PCSK9 and blocking the binding of PCSK9 to a particular cholesterol receptor, LDLR.”
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, 2, 6, 7, 11, 12, 14, 17 and 37 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.
Claims 1 and 14 are indefinite for “derivatives” and “prodrugs” as the specification does not provide for a reasonable definition or enough adequate species to define structures for derivatives or prodrugs for the claim in terms of the structures they would encompass. In addition, applicant uses the broad terminology of metabolites in claims 1 and 2, which would present further numerous variations of compounds. Therefore, it is unclear what the metes and bounds are for reading derivatives or prodrugs, which are meant to be options provided in addition to the metabolite itself. 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.
Claims 2, 6, 7, 11, 12, 17 and 37 are rejected as being dependent on an indefinite claim. Each of these claims still has the option of being a prodrug or derivative.
Claim 1 is indefinite for “one or more metabolites; derivatives, prodrugs, or pharmaceutical salts thereof” as it is unclear if applicant is say that there should be derivatives of the one or more metabolites, prodrugs of the one or more metabolites, or salts thereof (for all those items) or if applicant means there to be the options of “metabolites, derivatives or prodrugs or salts thereof” where metabolites, derivative and prodrugs represent separate unique items to choose from and then the option of their salts. Applicant may consider using the language “one or more metabolites, derivatives of the one or more metabolites, prodrugs of the one or more metabolites, or pharmaceutical salts thereof”, so they all refer back to the one or more metabolites.
Claims 2, 6, 7, 11, 12, 17 and 37 are rejected as being dependent on an indefinite claim.
Claim 2 is indefinite for “is shown in figure 1” as it is unclear what item, items or portion of figure 1 is being referred to. If applicant is referring to the compounds in figure 1, then they may construct a group of the compounds for this option in the claim. For the purpose of compact prosecution, the examiner would consider it as being toward any compounds that are found in the figure.
Claims 6 and 17 are rejected as being dependent on an indefinite claim.
Claims 6 and 17 are limitations to the prodrug structures, but it is not clear if applicant is just limiting the option prodrug compound as found in claim 2 (claim 2 uses and/or for options) or if applicant means to have the prodrug compound as a necessary part of the composition when reading these claims. There is no wording in the claims that indicates “wherein the composition comprises the prodrug compound and…”. Thus, it is unclear if applicant meant that to be the case or if the prodrug compound remains optional as introduced in claim 2, but with the further definitions. For the purpose of compact prosecution in the prior art, the examiner will consider these claims as still being part of the option which may or may not be chosen. However, the species election is noted to be one of the prodrugs and the examiner will consider the limitations in terms of this as well.
Regarding claim 7, the phrase "for example", the parenthetic with e.g. in this instance, 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).
Regarding claim 7, the phrase is incomplete, and thus, it is indefinite what the metabolite is associated with to read the claim. For the purpose of compact prosecution, if the association is with any item in the manner of the parenthetical, it will read on the claim.
Claim 7 recites the limitation "the metabolite" in the claim with the recitation in claim 1 being “one or more metabolites”. There is insufficient antecedent basis for this limitation in the claim. Applicant may amend the claim to be “the one or more metabolites”.
Claim 11 recites the limitation "the biodegradable agent" in the claim without a first mention of “a biodegradable agent” in the claim or one of the claims it depends on. There is insufficient antecedent basis for this limitation in 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 14 is indefinite for “DOPE@liposome” as it is unclear what the @ means for how the DOPE is part of the liposome since there would be different ways they might be associated. It is unclear if @ is to be interpreted as one type of association or if it can be various types of associations in chemistry.
Claim 17 is indefinite as there is no “and” or “or” between the end of the definition of R4 and just before “wherein R5”. Reading with “or” means that only one of the definitions has to be met while reading with “and” means all the definitions of the R groups have to be met. For the purpose of compact prosecution, the examiner will consider the claim with “or” as the conjunction for these R group definitions.
Regarding claim 37, the phrase "for example", the parenthetic with e.g. in this instance, 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).
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.
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.
Claims 6 and 17 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. Claims 6 and 17 provide for compounds with R5 that is hydrogen (H), while claim 2 on which they depend, does not provide hydrogen as a group for R5. Thus, compounds in claims 6 and 17 do not limit the compound structure in claim 2 as they extend to compound where R5 can be hydrogen. 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 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.
Claims 1, 2, 6, 7 and 17 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Tantawy et al (PharmaNutrition, 2019, volume 8, pages 1-5).
The composition in claim 1 only requires the metabolite; derivative, prodrug or pharmaceutical salt thereof. It is noted that claims 6 and 17 provide limitations to the optional component of the prodrug in claim 2, but the claims do not incorporate it into the composition, so they remain optional.
Tantawy teaches natural metabolites, arginine, histidine and tryptophan that have therapeutic function (abstract and pages 2-3).
Claims 1, 2, 6, 7 and 17 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Doherty US6008372A.
It is noted that claim 17 provide limitations to the optional component of the prodrug in claim 2, but the claim does not incorporate it into the composition, so they remain optional.
Doherty teaches Substituted histidine compounds of formula (I) (abstract). Example 6 teaches pi-N-methyl histidine methyl ester dihydrochloride, which is the compound of applicant claim 6, second to last compound. The pi bond is the nitrogen on the histidine ring closest to where the ring attaches to the alkyl chain of the amino acid.
Claims 1, 2, 6, 7, 11, 12, 14, and 17 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Li et al (International Journal of Nanomedicine, 2019, volume 2019, pages 3503-3516).
The composition in claim 1 only requires the metabolite; derivative, prodrug or pharmaceutical salt thereof. It is noted that claims 6 and 17 provide limitations to the optional component of the prodrug in claim 2, but the claims do not incorporate it into the composition, so they remain optional.
Li teaches arginine based liposomes (title and abstract and materials and methods). Li teaches the size distributions of 80-200 nm for the liposomes (abstract). Thus, Li teaches liposomes of nanometer size that have arginine, which is a metabolite.
Claims 1, 2, 6, 7, 17 and 37 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by He et al (Cancer Biol Ther, 2017, volume 18, pages 94-100).
The composition in claim 1 only requires the metabolite; derivative, prodrug or pharmaceutical salt thereof. It is noted that claims 6 and 17 provide limitations to the optional component of the prodrug in claim 2, but the claims do not incorporate it into the composition, so they remain optional.
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.
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.
Claims 2, 6, 7, 11, 14, and 17 in addition to claim 1 are rejected under 35 U.S.C. 103 as being unpatentable over Doherty US6008372A.
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.
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.
Non-Statutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1, 2, 6, 7, 17 and 37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 17, 58, 62 and 81 of copending Application No. 17/762,980 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘980 also provide for compounds that are metabolites or derivatives thereof such as glycerol and oligosaccharides as well as motivations to combine with vaccines or cancer immunotherapies. As noted above, claims 6 and 17 are still in optional form as the claims do not provide for them having to be part of the composition, but only provide limitations to the given option from claim 2.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusions
No claim is found allowable.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613