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 .
Response to Amendments
Applicant’s amendments to the claims of March 6, 2026, in response to the Office Action of November 7, 2026, is acknowledged.
Response to Arguments
Applicant argues that the prior art does not teach stimulating an immune response in a subject. Further, Applicant argues unexpected results are shown in Figure 5. In particular, Applicant notes in that the combination of Dimate and an anti-PDL-1 compounds shows a synergy in a colorectal model.
The examiner notes that unexpected results have not been provided for the following reasons. The claims are not commensurate in scope in a variety of ways with respect to the allegations of unexpected results. The claims are not limited to LNP-Dimate in combination with a specific anti-PDL1 compound. Further, there is no claim limited to colorectal cancer. However, even if they were, it is not clear what anti-PDL1 compound was used. It is also not clear when looking at Figure 5B that a synergy is presented. The graphs appear to show an additive effect. Further, anti-PDL1 compounds are known to allow a patient’s own immune cells to attack a cancer and make it vulnerable to other chemotherapies and treatments. Thus, any greater than additive effect that is alleged must also be unexpected and this may or may require showing more than just an additive effect. Two references are set forth below that provide some insight into the state of the art with respect to PDL-1 inhibition and treating cancer.
Song et al., “Future of anti-PD-1/PD-L1 applications: Combinations with other therapeutic regimens,” Chin J Cancer Res. 2018 Apr;30(2):157-172, teaches inhibiting PDL-1 and PD-1 is known to benefit colorectal cancer cells, melanoma, and others types of cancer. Further, potential therapeutic regimes known to synergize with inhibiting PDL-1 are discussed as they “may yield synergistic” outcomes.
Page et al., “Two may be better than one: PD-1/PD-L1 blockade combination approaches in metastatic breast cancer,” Nature Partner Journals (2019) 34, teaches PD-1 and PDL-1 inhibitors provide preclinical evidence of therapeutic synergy. Cytotoxic chemotherapy may synergize with antiPD-1/L1 agents. See p1, par.’s 1-2. For example, PARPi have a synergistic effect with PD-1 inhibition. See p5, 2nd par. Similarly, HDACi have also been found to synergize. See p34, 2nd full par. A number of different chemotherapeutic agents have demonstrated a synergy across therapeutic modalities. See p34, 4th full par.
Figure 5B shows what appears to be no more than an additive effect on tumor volume in the lung cancer model. Anti-PDL1 therapy alone drops tumor volume to 1000 mm3 from approximately 1800 and LNP-Dimate appears to decrease tumor volume from about 1800 to about 1250. Thus a decrease of 800 and 550 would appear to be additive. This would yield a tumor volume of less than 500. Similar data appears to be shown for melanoma and colon cancer. For the colon cancer Figure, it appears that LNP alone provides for a lower tumor volume than LNP-Dimate. Clarification is requested. Data should be provided that shows the statistical significance of the combination as compared to each agent alone. Further, the specific PDL-1 inhibitor should be set forth. Figure 5B appears to provide more relevant data than Figure 5A as it shows in vivo data.
As such, without data provided to show a statistical significance and an explanation how such showing is unexpected in view of the recognition of common synergies with anti-PDL-1 agents, it is not clear that a synergy has been shown for the claimed combination. Further, the data should control for LNP, DIMATE, and the combination. Even further, any showing must be commensurate in scope with the breadth of the claims. In this case, there is no a single claim limited to: LNP-Dimate in combination with an anti-PDL1 agent for treating a specific type of cancer. Without such showing, the examiner is merely determining if a prima facie showing has been established for the record.
The claimed agents are taught to treat the claimed forms of cancer. When these agents are administered to a subject, the “stimulating an immune response” would result, absent evidence to the contrary. As a final note, Fournet teaches administration of a lipid nanosphere administration for DIMATE.
Suggestions for Allowance: Applicant can limit the claims to treating lung, colon, breast, myeloma, and AML with a compound of Formula (I), wherein R1 or R2 is methyl and the other is CHR5CHR6OR4. Further, Applicant should file a TD over 17/631,046.
Status of the Claims
Claims 1-7, 11, 12, 14, 16, 17, and 19 are pending and examined.
Claim Rejections - 35 USC § 112
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, because the specification, while being enabling for treatment of those cancers set forth in claim 15, does not reasonably provide enablement for treatment of the claimed forms of cancers. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to treat and prevent a subject population having a claimed condition. Treatment of specific forms of cancer is enabled. In particular, breast, lung, colon, melanoma, and AML are enabled.
In particular this Scope of Enablement Rejection applies to the following: Treatment of the breadth of cancers is not enabled.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue."
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. The nature of the invention
2. The state of the prior art
3. The predictability or lack thereof in the art
4. The amount of direction or guidance present
5. The presence or absence of working examples
6. The breadth of the claims
7. The quantity of experimentation needed, and
8. The level of skill in the art
The Nature of the Invention
The instant claims are drawn to prevention and treatment of all infectious pathologies, inflammatory, metabolic conditions, and cancers. Treatment, which is defined by the instant Specification to include “prevention” actually means to anticipate or counter in advance, to keep from happening, etc. and there is no disclosure as to how one skilled in the art can reasonably establish the basis and the type of subject to which the instant compounds and compositions can be administered in order to have the "preventive" effect for a patient suffering or susceptible to any inflammatory, metabolic condition, and cancers. Treatment of these conditions once a subject has been identified is broad.
The State of the Prior Art and the Predictability or lack thereof in the art
The state of the prior art is that the pharmacological art involves screening invitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific diseases/conditions by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent and treat one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The instantly claimed invention is highly unpredictable as discussed below: It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instantly claimed invention is highly unpredictable since one skilled in the art would recognize that in regards to the preventative effects of the instantly claimed compounds on a neurological disorder, whether or not depression, e.g., could possibly be prevented.
With regards to pharmaceutical compositions for and methods of preventing a neurological condition, there are various conditions that can ultimately cause depression or a neurological condition. Further, because of the broad range of individuals who can be affected by a neurodegenerative disease e.g., prevention of the disease is focused on a person’s risk of the same, which is not entirely predictable. It is known in the art that in order to establish a proper and effective prevention plan for any neurological condition using medication, it is necessary for a practitioner in the art area to establish definitively that a person is at risk for the same. No medications are disclosed in the art as being useful for the general prevention of such conditions without accounting for the particular cause of the disease and the specific patient population.
The Amount of Direction / Guidance Present and the Presence or Absence of Working Examples
The examples in the instant Specification begin on page 54 and end on page 60. The use of compounds are shown on different immune cell populations, including NK cells and a erythroleukemic cell as a target population. Cells were pretreated with DIMATE at 10 micromolar. A lipidic nanoparticle was formulation also with DIMATE. LNP-DIMATE was used to test the in vivo efficacy of compounds on three animal models, which are models for colon cancer, lung cancer, and melanoma. See p59. Compounds increased ROS, promoted granulopoiesis, increased neutrophil mobilization, and expression of CD1 1b. In patients with low neutrophil count, it was thought to promote neutrophil recovery. Macrophage activation and also shown to clear apoptotic cells, promote wound healing and mitigate inflammatory response. The working examples are focuses solely on treating colon cancer, lung cancer, and melanoma. See Figure 6. The examiner also notes that LNP-DIMATE is not claimed with the exception of claim 6. However, claim 6 includes many compounds in additional to DIMATE. There are no examples for the treatment or prevention of all cancers, infectious pathologies, metabolic disorders, etc.
The level of the skill in the art
The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art as described above, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine whether the compound exhibits the desired pharmacological activity. The amount of guidance or direction needed to enable the invention is inversely related to the degree of predictability in the art. In re Fisher, 839, 166 USPQ 24. Thus, although a single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements, in cases involving unpredictable factors, such as most chemical reactions and physiological activity, more teaching or guidance is required. In re Fishcher, 427 F.2d 839, 166 USPQ 24; Ex Parte Hitzeman, 9 USPQ 2d 1823.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to definitively determine the specific population of individuals who would need to be treated and would furthermore have to determine which of the claimed compounds would provide for the prevention and treatment of all infectious pathologies, inflammatory conditions, metabolic conditions, and cancers. To prevent and treat all of these conditions in any patient population, as the instant claims are drawn to, would require undue experimentation to both develop an animal model which would reasonably correlate with all forms of neurodegenerative and also to identify the portion of the population in which the instantly claimed compounds would need to necessarily be administered.
According to Xiao et al., “Emerging therapies in cancer metabolism,” Cell Metabolism, 35, August 8, 2023: “a single metabolic drug may only be effective in a subgroup of tumor cells.” See p1293, 2nd par.
According to Lillich et al., “Multi-Target Approaches in Metabolic Syndrome,” Front Pharmacol. 2021 Mar 12;11:554961, “Currently, there are no approved drugs that can reliably reduce multiple conditions associated with metabolic diseases over the long-term.”
According to the University of Kansas Cancer Center, “Prevention and Risk Reduction,” https://www.kucancercenter.org/outreach/prevention/preventable-cancers -(accessed November 5, 2025), “No cancer is 100% preventable,” which is especially true for head and neck, cervical, lung, skin, and other forms of cancer.
Thus, factors such as "sufficient working examples", "the level of skill in the art" and "predictability", etc. have been demonstrated to be sufficiently lacking in the instantly claimed methods. In view of the breadth of the claim, the chemical nature of the invention, and the lack of working examples regarding the activity of the claimed compounds, one having ordinary skill in the art would have to undergo an undue amount of experimentation to use the invention commensurate in scope with the claims.
The court in Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001, states that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated or prevented by the compound encompassed in the instant claims, with no assurance of success.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 4, and 7 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ceylan et al., (U.S. Pat. No. 10,406,125).
Ceylan teaches treating cancers with compounds including S-methyl 4-(dimethylamino)-4-methylpent-2-ynethioate or a pharmaceutically acceptable salt thereof, and more particularly the 4-(Dimethylamino)-4-methyl-2-pentynethioic acid S-methyl ester fumarate. See Abstract. This includes a compound of formula (I), wherein R1 and R2 are alkyl, phenyl or benzyl, e.g., and R3 is methyl. See col. 3, lines 47-60. Also see Table 1, a compound of which is shown below.
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The compound above is also known as DIMATE. These compounds can treat leukemias, melanomas, colon cancer, pancreatic cancer, and others. See col, 10, lines 55-60. The drug is taught to mitigate chemoresistance of cancer cells in combination. The APIs described can be used in a pharmaceutical composition with one or more excipients.
Claims 1, 2, 4, and 7-10 are anticipated by the prior art.
Claims 1, 2, 4, 5, and 7 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Fournet et al., (US20030181443).
Fournet teaches aminothiol esters for treating cancer and precancer, among others, from a core Formula (I). See Abstract. The compounds of claim 1 fall within the scope of Formula (I). See par. 14-20 and paragraph 30. Paragraph 33 teaches: 1- S-methyl 4-dimethylamino-4-methyl-2-pentynethioate. Further, Fournet teaches composition in the form of a lipid nanosphere or capsule. See par.’s 88 and 91.
As such, claims 1, 2, 4, 5, and 7 are anticipated by the prior art.
Claim Rejections - 35 USC § 103
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.
Claims 1-7, 11, 12, 14, 16, 17, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Ceylan et al., (U.S. Pat. No. 10,406,125), in view of Sobol et al., (US2019/0038713), in view of Walker et al., (US2013/0337046), in view of Hoarau et al., (US2005/0214378).
Ceylan teaches treating cancers with compounds including S-methyl 4-(dimethylamino)-4-methylpent-2-ynethioate or a pharmaceutically acceptable salt thereof, and more particularly the 4-(Dimethylamino)-4-methyl-2-pentynethioic acid S-methyl ester fumarate. See Abstract. This includes a compound of formula (I), wherein R1 and R2 are alkyl, phenyl or benzyl, e.g., and R3 is methyl. See col. 3, lines 47-60. Also see Table 1, a compound of which is shown below.
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The compound above is also known as DIMATE. These compounds can treat leukemias, melanomas, colon cancer, pancreatic cancer, and others. See col, 10, lines 55-60. The drug is taught to mitigate chemoresistance of cancer cells in combination. The APIs described can be used in a pharmaceutical composition with one or more excipients.
Ceylan does not teach a lipidic nanocapsule or immune checkpoint inhibitor combination therapy.
Walker teaches delivering aminothiol compounds to a subject in a delivery system that includes lipid-based delivery systems, nanocarriers, and nanogels, e.g. See prior art claim 7. Nanoparticles are referred to as nanovesicles, nanocarriers, or nanocapsules. See par. 63. Such administration is advantageous to the delivery.
Hoarau teaches lipid nanocapsules with a lipid core, an outer envelope (i.e., shell) with one hydrophilic surfactant and one lipophilic surfactant each of which are lipidic in nature- as carrier for an API. See Abstract. The oily core can have an oily fatty phase. See par. 146. It can be composed of Labrafac® (i.e., MCTs of caprylic/capric) acids. In one example, the ratio of MCTs to API is 552/35.3, which is ratio of well above 4. Further, the lipid core can comprise between 20% and 60%, and preferably between 25% and 50% of the nanocapsule. See par. 104. This falls entirely within the claimed range. The lipid nanocapsule can be used to treat solid tumors and circulating tumors, including leukemia and lymphoma. See par. 118 and 122.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, each of the claimed components of a lipid nanoparticle are known result effective variables. As such, a POSA would be able to optimize to arrive at the claimed concentrations through nothing more than routine experimentation.
Walker and Hoarau do not teach immunotherapy.
Sobol teaches treating cancers with an immune checkpoint inhibitor, including inhibitors of PD-1, PD-L1, PD-L2, and LAG-3 among others. See par. 8. Melanoma, colon cancer, lung cancer, leukemia, head and neck cancer, and others can be treated with these agents. See par. 12.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). In this case, the claimed compounds of formula (I) and specific immune checkpoint inhibitors are known and taught to treat the same forms of cancer. As such, using them together would be obvious with a reasonable expectation of success in view of their independent success in treat those same cancers when used individually.
With regard to claim 13, a POSA would immediately envisage simultaneous, sequential, or combined used as well as those spread out over a period of time in view of the known use of the compounds of Formula (I) and immune checkpoint inhibitors for a same subject population.
With regard to the claims directed to a results of administration, the examiner notes that when a claimed agent is administered at an optimized dosage to a claimed subject population, a result of that administration would be expected to occur, absent evidence to the contrary.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to combined the teachings of Ceylan, Walker, Hoarau, and Sobol to arrive at the claimed product and methods. One would be motivated to do so because Ceylan teaches the claimed aminothiol ester compounds for treating cancers as part of combination therapy with an additional agent. Further, Walker teaches aminothiol compounds to be advantageous administered as a nanocapsules with an anti-cancer API. Moreover, Hoarau teaches nanocapsule formulations comprising the claimed components. Thus, the aminothiolester compound would be administered in a form of lipid nanocapsule in view of the teachings of Walker and Hoarau. Additionally, immune checkpoint inhibitors, including those types claimed, such as PD-1 inhibitors are taught to treat the same forms of cancers instant claimed. Thus, combining the compounds taught by Ceylan and Sobol to treat lung or colon cancer, e.g., would be obvious in view of their independent ability to treat these same cancers. Further, administration in the form of a nanocapsule would be obvious in view of the known advantages of administering aminothiol compounds and anti-cancer agents generally in the form of a lipid nanoparticle/nanocapsule. As such, the use of claimed APIs in a known form for treating cancers has a reasonable and predictable expectation of success.
Claims 1-7, 11, 12, 14, 16, 17, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Ceylan et al., (U.S. Pat. No. 10,406,125), in view of Sobol et al., (US2019/0038713), in view of Fournet et al., (US20030181443), and in view of Hoarau et al., (US2005/0214378).
Ceylan teaches treating cancers with compounds including S-methyl 4-(dimethylamino)-4-methylpent-2-ynethioate or a pharmaceutically acceptable salt thereof, and more particularly the 4-(Dimethylamino)-4-methyl-2-pentynethioic acid S-methyl ester fumarate. See Abstract. This includes a compound of formula (I), wherein R1 and R2 are alkyl, phenyl or benzyl, e.g., and R3 is methyl. See col. 3, lines 47-60. Also see Table 1, a compound of which is shown below.
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The compound above is also known as DIMATE. These compounds can treat leukemias, melanomas, colon cancer, pancreatic cancer, and others. See col, 10, lines 55-60. The drug is taught to mitigate chemoresistance of cancer cells in combination. The APIs described can be used in a pharmaceutical composition with one or more excipients.
Similarly, Fournet teaches aminothiol esters for treating cancer and precancer, among others, from a core Formula (I). See Abstract. The compounds of claim 1 fall within the scope of Formula (I). See par. 14-20 and paragraph 30. Paragraph 33 teaches 1- S-methyl 4-dimethylamino-4-methyl-2-pentynethioate. Further, Fournet teaches composition in the form of a lipid nanosphere or capsules. See par.’s 88 and 91.
Hoarau teaches lipid nanocapsules with a lipid core, an outer envelope (i.e., shell) with one hydrophilic surfactant and one lipophilic surfactant each of which are lipidic in nature- as carrier for an API. See Abstract. The oily core can have an oily fatty phase. See par. 146. It can be composed of Labrafac® (i.e., MCTs of caprylic/capric) acids. In one example, the ratio of MCTs to API is 552/35.3, which is ratio of well above 4. Further, the lipid core can comprise between 20% and 60%, and preferably between 25% and 50% of the nanocapsule. See par. 104. This falls entirely within the claimed range. The lipid nanocapsule can be used to treat solid tumors and circulating tumors, including leukemia and lymphoma. See par. 118 and 122.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, each of the claimed components of a lipid nanoparticle are known result effective variables. As such, a POSA would be able to optimize to arrive at the claimed concentrations through nothing more than routine experimentation.
Hoarau do not teach immunotherapy.
Sobol teaches treating cancers with an immune checkpoint inhibitor, including inhibitors of PD-1, PD-L1, PD-L2, and LAG-3 among others. See par. 8. Melanoma, colon cancer, lung cancer, leukemia, head and neck cancer, and others can be treated with these agents. See par. 12.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). In this case, the claimed compounds of formula (I) and specific immune checkpoint inhibitors are known and taught to treat the same forms of cancer. As such, using them together would be obvious with a reasonable expectation of success in view of their independent success in treat those same cancers when used individually.
With regard to claim 13, a POSA would immediately envisage simultaneous, sequential, or combined used as well as those spread out over a period of time in view of the known use of the compounds of Formula (I) and immune checkpoint inhibitors for a same subject population.
With regard to the claims directed to a results of administration, the examiner notes that when a claimed agent is administered at an optimized dosage to a claimed subject population, a result of that administration would be expected to occur, absent evidence to the contrary.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to combined the teachings of Ceylan, Fournet, Hoarau, and Sobol to arrive at the claimed product and methods. One would be motivated to do so because Ceylan teaches the claimed aminothiol ester compounds for treating cancers as part of combination therapy with an additional agent. Further, Walker teaches aminothiol compounds to be advantageous administered as a nanocapsules with an anti-cancer API. Moreover, Hoarau teaches nanocapsule formulations comprising the claimed components. Thus, the aminothiolester compound would be administered in a form of lipid nanocapsule in view of the teachings of Fournet and Hoarau. Additionally, immune checkpoint inhibitors, including those types claimed, such as PD-1 inhibitors are taught to treat the same forms of cancers instant claimed. Thus, combining the compounds taught by Ceylan and Sobol to treat lung or colon cancer, e.g., would be obvious in view of their independent ability to treat these same cancers. Further, administration in the form of a nanocapsule would be obvious in view of the known advantages of administering aminothiol compounds and anti-cancer agents generally in the form of a lipid nanoparticle/nanocapsule. As such, the use of claimed APIs in a known form for treating cancers has a reasonable and predictable expectation of success.
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.
Claims 1-7, 11, 12, 14, 16, 17, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 10,406,125, in view of Sobol et al., (US2019/0038713), in view of Walker et al., (US2013/0337046), in view of Hoarau et al., (US2005/0214378) for the reasons set forth below.
Claims 1-7, 11, 12, 14, 16, 17, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 10,570,089, in view of Sobol et al., (US2019/0038713), in view of Walker et al., (US2013/0337046), in view of Hoarau et al., (US2005/0214378) for the reasons set forth above.
Ceylan (i.e., the ‘125 patent) does not teach a lipidic nanocapsule or immune checkpoint inhibitor combination therapy.
Rool (i.e., the ‘089 patent) teaches a method to make compounds of Formula (I), but also does not teach a lipidic nanocapsule or immune checkpoint inhibitor combination therapy.
Walker teaches delivering aminothiol compounds to a subject in a delivery system that includes lipid-based delivery systems, such as nanocarriers, and nanogels, e.g. See prior art claim 7. Nanoparticles are referred to as nanovesicles, nanocarriers, or nanocapsules. See par. 63. Such administration is advantageous to the delivery.
Hoarau teaches lipid nanocapsules with a lipid core, an outer envelope (i.e., shell) with one hydrophilic surfactant and one lipophilic surfactant each of which are lipidic in nature- as carrier for an API. See Abstract. The oily core can have an oily fatty phase. See par. 146. It can be composed of Labrafac® (i.e., MCTs of caprylic/capric) acids. In one example, the ratio of MCTs to API is 552/35.3, which is ratio of well above 4. Further, the lipid core can comprise between 20% and 60%, and preferably between 25% and 50% of the nanocapsule. See par. 104. This falls entirely within the claimed range. The lipid nanocapsule can be used to treat solid tumors and circulating tumors, including leukemia and lymphoma. See par. 118 and 122.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Here, each of the claimed components of a lipid nanoparticle are known result effective variables. As such, a POSA would be able to optimize to arrive at the claimed concentrations through nothing more than routine experimentation.
Walker and Hoarau do not teach immunotherapy.
Sobol teaches treating cancers with an immune checkpoint inhibitor, including inhibitors of PD-1, PD-L1, PD-L2, and LAG-3 among others. See par. 8. Melanoma, colon cancer, lung cancer, leukemia, head and neck cancer, and others can be treated. See par. 12.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). In this case, the claimed compounds of formula (I) and specific immune checkpoint inhibitors are known and taught to treat the same forms of cancer. As such, using them together would be obvious with a reasonable expectation of success in view of their independent success in treat those same cancers when used individually.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to combined the teachings of Ceylan, Walker, Hoarau, and Sobol to arrive at the claimed product and methods. One would be motivated to do so because Ceylan teaches the claimed aminothiol ester compounds for treating cancers as part of combination therapy with an additional agent. Further, Walker teaches aminothiol compounds to be advantageous administered as a nanocapsules with an anti-cancer API. Moreover, Hoarau teaches nanocapsule formulations comprising the claimed components. Thus, the aminothiolester compound would be administered in a form of lipid nanocapsule in view of the teachings of Walker and Hoarau. Additionally, immune checkpoint inhibitors, including those types claimed, such as PD-1 inhibitors are taught to treat the same forms of cancers instant claimed. Thus, combining the compounds taught by Ceylan and Sobol to treat lung or colon cancer, e.g., would be obvious in view of their independent ability to treat these same cancers. Further, administration in the form of a nanocapsule would be obvious in view of the known advantages of administering aminothiol compounds and anti-cancer agents generally in the form of a lipid nanoparticle/nanocapsule. As such, the use of claimed APIs in a known form for treating cancers has a reasonable and predictable expectation of success.
Claims 1-7, 11, 12, 14, 16, 17, and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8, 9, 11, 13, and 16 of copending Application No. 17/631,046, in view of Ceylan et al., (U.S. Pat. No. 10,406,125), in view of Sobol et al., (US2019/0038713), in view of Fournet et al., (US20030181443), and in view of Hoarau et al., (US2005/0214378) for the reasons set forth above.
. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims include a substantial number of overlapping compounds in addition to treating many of the same cancers in claim 13 of the ‘046 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
As such, no claim is allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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 extension fee 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.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
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