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 the Claims
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/22/2025 has been entered.
Claims 2-4 are cancelled.
Claims 7-20 are withdrawn.
Claims 1 and 5-6 are under current examination.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Specification
The amendment filed 08/22/2025 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows:
The amendments that the lycopene is combined/mixed with the ZIF-90 MOF material, rather than bound to the ZIF-90 MOF material through aldol condensation/mixed to conduct aldol condensation (see paragraphs [0008], [0014], [0021], [0033], [0046]); the amendments at paragraphs [0054]-[0055] that post-treatment is conducted on a resulting system rather than on a solution that has undergone aldol condensation; and the amendments at paragraphs [0076], [0084], and [0094] that a system rather than a solution is obtained during the preparation of LYC@ZIF-90.
The amendment of lycopene being combined/mixed with the ZIF-90 MOF material is broader in scope than the original disclosure of lycopene being bound through aldol condensation/mixed to conduct aldol condensation. The amendments that post-treatment is conducted on a resulting system is broader in scope than the original disclosure of conducting post-treatment on a solution that has undergone an aldol condensation reaction. The amendment that a system is obtained during the preparation of LYC@ZIF-90 is broader in scope than the original disclosure of a solution.
Applicant is required to cancel the new matter in the reply to this Office Action.
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.
Claims 1 and 5-6 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contain 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, at the time the application was filed, had possession of the claimed invention.
MPEP 2163 provides guidelines for examination of patent applications for compliance with the written description requirement. Per MPEP 2163 II. A. 1., “Claim construction is an essential part of the examination process. Each claim must be separately analyzed and given its broadest reasonable interpretation in light of and consistent with the written description. See, e.g., In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303, 1319-1320, 97 USPQ2d 1737, 1750 (Fed. Cir. 2011)”.
In the present instance, claim 1 recites the limitation “the LYC/ZIF-90 nanocomposite comprises a ZIF-90 metal-organic framework (MOF) material and LYC combined with the ZIF-90 MOF material”; claims 5-6 limit the pore size and particle size of the nanocomposite. The specification-as-filed refers to lycopene “combined with” the ZIF-90 MOF “through aldol condensation” (paragraph [0021]). Throughout the specification, the nanocomposite is described as lycopene bound to the ZIF-90 MOF material through aldol condensation (see paragraphs [0008], [0021], [0033]). Thus, giving the claims their broadest reasonable interpretation in light of and consistent with the written description, the limitation of the MOF material “combined with” LYC is inclusive of the MOF and LYC materials chemically bound to each other through aldol condensation.
MPEP 2163 further states that possession may be shown in many ways, including an actual reduction to practice. MPEP 2163 3.(a) i) states (emphasis added), “Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
In the present instance, the specification-as-filed provides examples of the preparation of LYC@ZIF-90 which involve dissolving LYC in methanol, adding the ZIF-90 MOF material, and stirring at room temperature (paragraph [0077], [0086], and [0095]). The specification-as-filed states that this mixing conducts an aldol condensation to obtain an LYC/ZIF-90 nanocomposite (paragraphs [0014], [0046]), and “during the aldol condensation, an aldehyde group of the ZIF-90 and a hydroxyl group of the LYC are ligated through condensation” (paragraph [0054]).
However, a person of ordinary skill in the art would recognize that lycopene is known in the prior art as a hydrocarbon with a molecular formula of C40H56 and the following structure, which does not comprise a hydroxyl group (Figure 1 from Khan et al. “Lycopene: Food Sources, Biological Activities, and Human Health Benefits”; of record):
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Lycopene contains 11 conjugated and 2 non-conjugated double bonds; it is insoluble in water, ethanol, and methanol (Falsafi, “Lycopene nanodelivery systems; recent advances”, pg. 379, “2.1. Structural Features”; of record).
A person of ordinary skill in the art would further recognize that aldol condensation reactions are known to take place as a reaction between molecules containing aldehyde or ketone functional groups; the general reaction conditions involve reaction of an aldehyde (or ketone) enolate with another molecule of the aldehyde (or ketone) in the presence of an acid or base catalyst, such as NaOH or KOH, followed by a dehydration/elimination reaction (Millipore Sigma, “Aldol Condensation Reaction”, pg. 1; of record). As noted above, lycopene is a hydrocarbon with a molecular formula of C40H56 and does not possess any aldehyde or ketone functional groups. There is no expectation from the teachings of the art that it would participate in an aldol condensation reaction. Further, as noted above, lycopene is known to be insoluble in alcohol solvents, including methanol.
In view of the above, with particular emphasis on the disclosed method of making the claimed invention, the specification does not reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention as a whole. Accordingly, claims 1 and 5-6 fail to comply with the written description requirement.
Claim Rejections - 35 USC § 112(a)-Enablement
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.
Claims 1 and 5-6 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. MPEP 2164.01(a), citing In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), sets out the factors to consider whether experimentation is undue and further states “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)”. These factors include:
(A) The breadth of the claims. Claim 1 is drawn to a testis-targeted lycopene (LYC)/ZIF-90 nanocomposite wherein the LYC/ZIF-90 nanocomposite comprises a ZIF-90 metal-organic framework (MOF) material and LYC combined with the ZIF-90 MOF material. “Combined with” is a broad recitation and, absent a specific definition in the specification, is inclusive of the MOF and LYC materials chemically bound to each other. The claim further recites follicle-stimulating hormone loaded on a surface and internal pores of the LYC/ZIF-90 nanocomposite and recites mass ratio ranges of the components. Claims 5-6 limit the pore size and particle size of the nanocomposite.
(B) The nature of the invention. The claims are drawn to a nanocomposite wherein lycopene is combined with a ZIF-90 MOF. The specification-as-filed refers to lycopene “combined with” ZIF-90 MOF “through aldol condensation” (paragraph [0021]). Throughout the specification, the nanocomposite is described as lycopene bound to the ZIF-90 MOF material through aldol condensation (paragraphs [0008], [0021], [0033]). This is carried out by mixing the ZIF-90 MOF material and the LYC with an alcohol solvent to conduct aldol condensation to obtain an LYC/ZIF-90 nanocomposite (paragraphs [0014], [0046]), and “during the aldol condensation, an aldehyde group of the ZIF-90 and a hydroxyl group of the LYC are ligated through condensation” (paragraph [0054]). Examples of the preparation of LYC@ZIF-90 involve dissolving LYC in methanol, adding the ZIF-90 MOF material, and stirring at room temperature (paragraph [0077], [0086], and [0095]).
(C) The state of the prior art. Lycopene is known in the prior art as a hydrocarbon with a molecular formula of C40H56 and the following structure (Figure 1 from Khan et al. “Lycopene: Food Sources, Biological Activities, and Human Health Benefits”; of record):
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Lycopene contains 11 conjugated and 2 non-conjugated double bonds; it is insoluble in water, ethanol, and methanol (Falsafi, “Lycopene nanodelivery systems; recent advances”, pg. 379, “2.1. Structural Features”; of record).
(D) The level of one of ordinary skill. The level of ordinary skill in the art is assumed to be that of one having knowledge and experience in the fields of chemistry and/or biochemistry. The ordinary skilled artisan would understand the principles of chemical reactivity and how chemical species combine with each other.
(E) The level of predictability in the art. Aldol condensation reactions are known to take place as a reaction between molecules containing aldehyde or ketone functional groups; the general reaction conditions involve reaction of an aldehyde (or ketone) enolate with another molecule of the aldehyde (or ketone) in the presence of an acid or base catalyst, such as NaOH or KOH, followed by a dehydration/elimination reaction (Millipore Sigma, “Aldol Condensation Reaction”, pg. 1; of record). As noted above, lycopene is a hydrocarbon with a molecular formula of C40H56 and does not possess any aldehyde or ketone functional groups. There is no expectation from the teachings of the art that it would participate in an aldol condensation reaction. In this sense, in the context of making a nanocomposite comprising lycopene “combined with” a ZIF-90 MOF material through the aldol condensation described in the instant specification, the level of unpredictability is extremely high.
Further, as noted above, lycopene is known to be insoluble in alcohol solvents, including methanol. Therefore, in the context of making a nanocomposite comprising lycopene “combined with” a ZIF-90 MOF material via the dissolution of lycopene in methanol described in the instant specification, the level of unpredictability is extremely high.
Further, as noted above, lycopene is a hydrocarbon that contains 11 conjugated and 2 non-conjugated double bonds. Typical reactions involving alkenes require the presence of acids, halogens, catalysts and/or heat (see Chemistry LibreTexts “16.3: Summary of Alkene Reactions”; of record). Therefore, in the context of making a nanocomposite comprising lycopene combined with a ZIF-90 MOF material through aldol condensation via stirring lycopene with ZIF-90 in methanol at room temperature absent any additional reactants or catalysts, the level of unpredictability is extremely high.
(F) The amount of direction provided by the inventor. The sole reference in the specification-as-filed to a ZIF-90 MOF material “combined with” lycopene is in the context of the components being combined “through aldol condensation” (paragraph [0021]). As noted above, throughout the specification, the nanocomposite is described as lycopene bound to the ZIF-90 MOF material through aldol condensation (paragraphs [0008], [0021], [0033]).
Further, the specification states that during the aldol condensation, an aldehyde group of the ZIF-90 and a hydroxyl group of the LYC are ligated through condensation (paragraph [0054]). As described above, and as noted in the instant specification (paragraph [0004]), lycopene has a molecular formula of C40H56, and does not contain a hydroxyl group. As further noted above, aldol condensation reactions occur between molecules containing aldehyde or ketone functional groups, not hydroxyls.
The specification further provides examples of the preparation of LYC@ZIF-90 which involve dissolving LYC in methanol (paragraph [0077], [0086], and [0095]). As described above, lycopene is known to be insoluble in methanol.
Thus, the inventor has not provided adequate direction on how to make the claimed nanocomposite comprising LYC combined with ZIF-90 commensurate with the full scope of the claims.
(G) The existence of working examples. The specification does not provide evidence that the procedures described (for example at paragraphs [0046], [0054], [0077], [0086], and [0095]) result in a lycopene/ZIF-90 nanocomposite with lycopene “combined with” the ZIF-90 MOF material in the context of the components being combined “through aldol condensation” (as set forth in the specification-as-filed at paragraph [0021]).
The data presented in Figures 3 and 4 of the instant specification would not indicate to one of ordinary skill in the art that lycopene has been combined through aldol condensation with the ZIF-90 material, as all of the structural features of the ZIF-90 appear to be retained in the LZF spectra. The specification notes that Fig. 4 shows that an aldehyde group in the material was not destroyed (paragraph [0106]), contrary to the previous statement that an aldehyde group of the ZIF-90 and a hydroxyl group of the LYC are ligated through condensation (paragraph [0054]). The data presented therefore indicates that no combination has occurred via the aldehyde group of the ZIF-90 material.
(H) The quantity of experimentation needed to make or use the invention. There is no expectation that lycopene will dissolve in methanol or participate in an aldol condensation reaction. This, coupled with coupled with a lack of direction and evidence provided by the instant disclosure that the procedures described would result in lycopene that is combined with the ZIF-90 material through aldol condensation, indicates that a skilled artisan could not make a lycopene/ZIF-90 nanocomposite commensurate with the full scope of the claims without undue experimentation.
Given the above, with particular emphasis on the lack of adequate direction on how to make the claimed nanocomposite, the claims fail to comply with the enablement requirement.
Response to Arguments
Applicant’s arguments filed 08/22/2025 have been fully considered.
Regarding the previous objection to the specification, Applicant submits a substitute specification and submits that the amendments obviate the objection. For example, “an obtained mixture” is changed to “a resulting system”; Applicant argues that since the aldol condensation of the ZIF-90 MOF material and the LYC is impossible to occur, it is impossible to obtain a solution that has undergone aldol condensation, and only a resulting system after mixing is obtained for the next step.
In response, and as detailed above, the Examiner notes that the substitute specification is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. The amendments are broader in scope than the original disclosure.
Regarding the previous rejections under 35 USC § 112(a), Applicant argues that Applicant has amended “physically bound to” to “combined with” and that support for the amendment is found in the abstract and paragraph [0021] of the specification as filed. Applicant submits that the amended claims are sufficiently enabled as “combined with” does not mean that a chemical bond has formed but that LYC is combined with the ZIF-90 MOF material via physical interaction, and the success of physically binding is confirmed by Figure 7 of the present application. Regarding the solubility of lycopene, Applicant argues that lycopene is almost insoluble in methanol, not completely insoluble, and the degree of solubility is determined by many factors including the ratio of lycopene to methanol and whether sonicated; complete dissolution does not largely affect the preparation of the nanocomposite. Applicant argues that the specification has been “adaptively amended” by deleting obviously-wrong expressions; one of ordinary skill in the art would find that the present disclosure reasonably conveys that the inventors had possession of the claimed subject matter as of the filing date and provides adequate direction on how to make the claimed nanocomposite.
In response, the Examiner first notes that the amendments to the specification are broader in scope than the original disclosure and introduce new matter; the Examiner thus refers to the specification-as-filed in the current rejections. As detailed above, the specification refers to lycopene “combined with” ZIF-90 MOF “through aldol condensation” (paragraph [0021]); giving the claims their broadest reasonable interpretation in light of and consistent with the written description, the limitation of the MOF material “combined with” LYC is inclusive of the MOF and LYC materials chemically bound to each other through aldol condensation.
As detailed above, the specification does not reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention as a whole, and the claims lack written description. As further detailed in the above rejections, with particular emphasis on the lack of adequate direction on how to make the claimed nanocomposite, a skilled artisan could not make a lycopene/ZIF-90 nanocomposite commensurate with the full scope of the claims without undue experimentation, and the claims fail to comply with the enablement requirement.
In response to the arguments regarding the solubility of lycopene in methanol, the Examiner maintains that the prior art of Falsafi (“Lycopene nanodelivery systems; recent advances”, pg. 379, “2.1. Structural Features”; of record) teaches that lycopene is insoluble in methanol. However, assuming en arguendo that lycopene has sparing solubility in methanol, the specification does not provide guidance regarding sonication or other experimental factors which convey to one of ordinary skill in the art such that a “methanol solution with a concentration of 5 mg/mL” is expected to be achieved during the disclosed method of making the claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUDITH M KAMM whose telephone number is (703)756-4575. The examiner can normally be reached M-F 8:00 am-4:30 pm EST.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/J.M.K./Examiner, Art Unit 1611