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 .
Claims 1-20 and 57 are pending in the Claim Set filed 5/11/2026.
Claims 21-56 are canceled.
Applicants’ election of species in the reply filed 5/11/20206 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse
(MPEP § 818.03(a)). Herein, the species election is withdrawn. The entire set of claims: 1-20 and 57, are examined for prosecution to promote compact prosecution.
No claim is withdrawn.
Claims 1-20 and 57 are for examination.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 1/23/2025, 1/23/2025 and 1/23/2025 was considered by the examiner.
Regarding Claims
Claims 4 and 12 contain the abbreviations 'PSMA', RSL3; and GPX, respectively, which are not defined by the claim. As stated in MPEP 2173.05(s)
'Where possible, claims are to be complete in themselves'. An abbreviation should be expanded when first used in Instant Claims in order to clarify the meaning of the abbreviation
Objection to Abstract
The Abstract filed 2/06/2024 states: The present disclosure describes methods of treatment (e.g., combination treatment) by ferroptotic induction, as well as compositions and dosing regimens that are part of such methods. Surprisingly, it is presently found that delaying administration of a ferroptosis-inducing agent until after starting hormone therapy results in enhanced ferroptotic induction in a subject. Thus, in certain embodiments, combination therapies are presented herein that include multiple administration steps whereby a ferroptosis-inducing agent is administered sometime after hormone therapy has begun.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, "The disclosure concerns," "The disclosure defined by this invention," "The disclosure describes," etc.
Also, vague words like ‘‘sometime’ should be avoided in the Abstract.
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.
Claims 1-20 and 57 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites:
A method of combination treatment of a subject, the method comprising:
a first step of administering an initial dose of a first agent to the subject; and
a second step of administering an initial dose of a second agent to the subject to induce ferroptosis of cancer cells,
wherein the step of administering the initial dose of the second agent occurs at a discrete period of time after the step of administering the initial dose of the second agent.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by the inventor. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that the inventors invented what is claimed.").
The broad genus subject matter comprising: (i) an initial dose of a first agent; (ii) initial dose of a second agent; (iii) administering a composition; (iv) cancer, would encompass a vast number of varied first agents as an initial dose, varied second agents as an initial dose, plethora of varied compositions, and array of variable cancers thereof, of which the amount of each first agent as an initial dose, of which the amount of each second agent as an initial dose, compositions comprising varied amounts of each first and second agent, and further comprising varied cancers and treatments, wherein claims 1, 39 and 50 are open-ended and do not exclude additional, unrecited elements or method steps thereof.
For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents" of the University of California v. Eli Lilly & Co. the court stated: "A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, or chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 197 3). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966. "Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The problem is especially critical with genus claims that use functional language to define the boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, as here: wherein the composition provides a therapeutically effective plasma concentration of the active pharmaceutical ingredient over a period of at least about 18 hours.
For claims drawn to a genus MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus, See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406, M.P.E.P. 2163.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Moreover, if the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. A description of what a material does, rather than of what it is, usually does not suffice. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. One cannot describe what one has not conceived.
The specification discloses a method of combination treatment of a subject (e.g., a subject having been diagnosed with cancer, e.g., prostate cancer), the method comprising: a first step of administering an initial dose of a first agent to the subject; and a second step of administering an initial dose of a second agent to the subject to induce ferroptosis of cancer cells (e.g., prostate cancer), wherein the step of administering the initial dose of the second agent occurs at a discrete period of time after the step of administering the initial dose of the second agent (e.g., a known period of time, e.g., greater than 12 hours, e.g., greater than 1 day, e.g., greater than 2 days, e.g., about 5 days, e.g., greater than 5 days, e.g., greater than 7 days, e.g., greater than 10 days, e.g., about 15 days) [0008] (e.g., wherein the first agent comprises an androgen inhibitor and wherein the androgen inhibitor causes increased expression of PSMA by prostate cancer cells (e.g., increased expression by prostate cancer cells than by normal prostate cells), e.g., wherein the second agent comprises a ferroptosis-inducing nanoparticle with a PSMA-targeting ligand [0011], e.g., wherein the increased expression of PSMA by the prostate cancer cells results in enhanced ferroptotic induction by the second agent, e.g., due to improved targeting of the ferroptosis-inducing nanoparticle to the prostate cancer cells), wherein the subject has also received an androgen inhibitor, e.g., via one or more separate doses ([0012]; [0028], wherein the first agent comprises an androgen inhibitor or other agent administered as part of hormone therapy [0029], wherein the method comprises administering the first agent to the subject on a daily basis. In certain embodiments, the first agent comprises an androgen inhibitor and wherein the androgen inhibitor causes increased expression of PSMA by prostate cancer cells (e.g., increased expression by prostate cancer cells than by normal prostate cells), wherein, the second agent comprises a ferroptosis-inducing nanoparticle with a PSMA targeting ligand [0030], wherein the invention is directed to a treatment comprising a therapeutically effective amount of a first agent (e.g., comprising an androgen inhibitor or other agent administered as part of hormone therapy) for use in combination with a second agent (e.g., wherein the second agent comprises a ferroptosis-inducing nanoparticle with a PSMIA-targeting ligand) for use in a method of treating cancer (e.g., prostate cancer) or preventing cancer occurrence or recurrence in a subject [0033], wherein the second agent comprises a nanoparticle, wherein the second agent comprises an inhibitor-functionalized ultra small nanoparticle; or, the second agent does not comprise a nanoparticle [0015-0016]; or, the second agent comprises a nanoparticle and a species associated with (e.g., bound to) the nanoparticle [0015-0017]. Further, the combination treatment comprises administering antibodies, such as anti-PD-1 or PD-L1, and/or their fragments) and/or one or more small molecule inhibitors; and/or (ii) one or more standard-of-care anti-androgen receptor therapeutics and/or a hypoxia-activated prodrug [0021], and wherein the hormone therapy comprises a member selected from the group consisting of (i) treatments to lower androgen levels (e.g., Orchiectomy (surgical castration), luteinizing hormone-releasing hormone (LHRH) agonists, LHRH antagonists (e.g., Degarelix (Firmagon), CYPl 7 inhibitors, and/or Abiraterone (Zytiga)), (ii) treatments to stop androgens from working (e.g., antiandrogens such as Enzalutamide, Apalutamide, Darolutamide, cyroterone, Androcur, Nilutamide, Bicalutamide), and (iii) other androgen-suppressing drugs (e.g., estrogens, ketoconazole) [0022], and wherein the cancer cells is selected from the group consisting of renal, prostate, melanoma, pancreatic, lung, fibrosarcoma, breast, brain, ovarian, and colon cancer cells [0020].
Although the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
Accordingly, in the instant case, the specification fails to describe the broad genus subject matter including an initial dose of a first agent; initial dose of a second agent; administering a composition; (iv) cancer, would encompass a vast number of varied first agents as an initial dose, varied second agents as an initial dose, plethora of varied compositions, and array of variable cancers thereof, of which the amount of each first agent as an initial dose, of which the amount of each second agent as an initial dose, compositions comprising varied amounts of each first and second agent, and further comprising varied cancers and treatments, wherein instant claims are open-ended and do not exclude additional, unrecited elements or method steps thereof.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic claim. However, it is unquestionable that the method of treatment of a subject comprises claims that are broad and generic, wherein the claims are open-ended such that the possible variations of first and second agents, varied compositions comprising first and second agents to provide a method of treatment of cancers are seemingly limitless of which do not have sufficient description in the specification.
Based on the foregoing, it is evident that the method of preparing a pharmaceutical composition comprising timed pulsatile release (TPR) beads, wherein said TPR beads comprise a solid dispersion of at least one active pharmaceutical ingredient in at least one solubility enhancing polymer; and a TPR coating comprising a water insoluble polymer and an enteric polymer; wherein the composition provides a therapeutically effective plasma concentration of the active pharmaceutical ingredient over a period of at least about 18 hours, as instantly claimed, embraces a broad genus of pharmaceutical compositions of which do not have sufficient description in the specification.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
Accordingly, it is deemed that the specification fails to provide adequate written description for ‘A method of combination treatment of a subject, the method comprising a first step of administering an initial dose of a first agent to the subject; and a second step of administering an initial dose of a second agent to the subject to induce ferroptosis of cancer cells, wherein the step of administering the initial dose of the second agent occurs at a discrete period of time after the step of administering the initial dose of the second agent and does not reasonably convey to one skilled in the relevant art that the inventor(s), have possession of the entire scope of the claimed invention as claimed in the Claim Set filed 5/11/2026. The remaining claims are rejected at least for the reason that they are dependent on a rejected claim.
Claim Rejections - 35 USC § 112
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 1-20 and 57 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 pre-AIA the applicant regards as the invention.
Claim 1 recites in part:
wherein the step of administering the initial dose of the second agent occurs at a discrete period of time after the step of administering the initial dose of the second agent.
This phrase is unclear. It appears that the terms ‘second agent’ refers to the same agent, whereas the claims are directed to a method of combination treatment of a subject. Thus, in view of this consideration, the recitation of the term ‘second agent’ should be considered or should be ‘the first agent,’ in accordance with an amendment as follows:
‘wherein the step of administering the initial dose of the second agent occurs at a discrete period of time after the step of administering the initial dose of the
The remaining claims are rejected as depending from a rejected claim.
Clarification is required.
Claims 1-20 and 57 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 pre-AIA the applicant regards as the invention.
Claims 1 recites in part:
The phrase: ‘a discrete period of time,’ of which would comprise minutes, hours, and days or even more, for example, months, and would also encompass varied ranges of time therein, for example, between 45 minutes to 2 hours.
Accordingly, the phrase: a discrete period of time, is indefinite because the ‘metes and bounds’ of the claim is unclear. The language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its ‘metes and bounds.’ The specification does not clearly set forth the metes and bounds of the discrete period of time.
The remaining claims are rejected as depending from a rejected claim.
Claims 2, 12 and 13 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 pre-AIA the applicant regards as the invention.
Claims 2 recites in part:
wherein the first agent comprises an androgen inhibitor or other agent administered as part of hormone therapy.
The terms ‘other agent’ is unclear, since it would not be clear to those skilled in the art whether ‘other agent’ refers to agent that is a different androgen inhibitor or whether the terms ‘other agent’ refer to an agent (e.g., a compound that is a hormone, e.g., alpha-MSH) that is a part of a hormone therapy.
Claim 12 and 13 recite ‘other compounds. Similarly, the terms ‘other compounds’ is unclear,
Clarification is required.
Claim 14 is 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 pre-AIA the applicant regards as the invention.
Claim 14 contains parenthetical subject matter that renders the claim indefinite because it is not clear whether: (i.e. the (and/or the spreading of cancer cell death) is a limitation or an option for the spreading of cancer cell death.
Claim 18 is 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 pre-AIA the applicant regards as the invention.
Claim 18 is rejected as being indefinite because the claim recites a Markush grouping of alternatives of the targeting ligands comprise a member selected from the group comprising of PSMAi and alpha-MSH using the transitional phrase "comprises' See, e.g., MPEP §2173.05(h), stating in part that, "Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. See also, MPEP 2111.03 stating in part that, 'comprising' is a term of art used in claim language which means that the named elements are essential, but other elements may be added and still form a construct within the scope of the claim. Thus, the term 'comprises' is confusing because the transitional phrase 'comprises' is typically read as meaning that each element following the transitional phrase is a required claim limitation.
The examiner suggests Applicants adopt the transitional phrase " the targeting ligands selected from group consisting of PSMAi and alpha-MSH.
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)(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, 7 and 9-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bradbury et al (WO2016196201, cited in IDS filed 1/13/2025) [Bradbury].
Regarding claims 1-3, 7 and 9-20,
Bradbury teaches a method of combinational treatment of a subject, the method comprising: depriving a tumor tissue (e.g., prostate cancer tissue) of hormones; and administering nanoparticles for accumulation at sufficiently high in the tumor tissue to induce ferroptosis. Bradbury teaches that the tumor tissue is selected from the group consisting of renal, prostate, melanoma, pancreatic, lung, fibrosarcoma, breast, brain, ovarian, and colon tumor tissue. In certain embodiments, the tumor pancreatic tissue comprises BxPC3 cells. In certain embodiments, the tumor lung tissue comprises HI650 cells (Abstract; [0021]; [0022]; [0027]; claim 16; See entire document).
Bradbury defines Combination Therapy: As used herein, the term "combination therapy" refers to those situations in which a subject is simultaneously exposed to two or more therapeutic regimens (e.g., two or more therapeutic agents). In some embodiments, two or more agents may be administered simultaneously; in some embodiments, such agents may be administered sequentially; in some embodiments, such agents are administered in overlapping dosing regimens [0048].
Further, Bradbury teaches the nanoparticles comprise 1-20 targeting moieties, where the targeting moieties bind to receptors on tumor cells (e.g., where the nanoparticles have an average diameter of 1-15 nm). The targeting moieties comprise alpha melanocyte-stimulating hormone (alpha-MSH) [0029]. Further, Bradbury teaches that the drug delivery combines with native immunomodulation properties of the administered nanoparticles (e.g., wherein the nanoparticles comprise a-MSHPEG-C' dots, e.g., wherein a-MSH is bound to a surface of the nanoparticles) (e.g., wherein the nanoparticles comprise an organic-polymer coating (e.g., polyethylene glycol (PEG))) to increase the therapeutic potential of C dots in cancer treatment and/or tissue repair processes (e.g., wound healing) ([0033]; claims 30, 31, 36). Brdabury teaches the nanoparticle comprises a radiolabel ([0050-0151]). Bradbury teaches ultrasmall poly(ethylene glycol) coated (PEGylated) near-infrared (NIR) fluorescent silica nanoparticle, referred to as C' dots [0005].
Bradbury teaches where combinational therapy is used, an embodiment therapeutic method includes administration of the nanoparticle and administration of one or more drugs (e.g., either separately, or conjugated to the nanoparticle), e.g., one or more chemotherapy drugs, such as sorafenib, paclitaxel, docetaxel, MEK162, etoposide, lapatinib, nilotinib, crizotinib, fulvestrant, vemurafenib, bexorotene, and/or camptotecin [0156], wherein the surface chemistry, uniformity of coating (where there is a coating), surface charge, composition, concentration, frequency of administration, shape, and/or size of the nanoparticle can be adjusted to produce a desired therapeutic effect, e.g., ferroptosis of cancer cells [0157].
Bradury in Figure 7J, shows that pretreatment with elastin sensitizes of erastin to nanoparticle-induced ferroptosis.
[0095] FIG. 7J 9Description) shows that pre-treatment with erastin sensitizes to nanoparticle-induced ferroptosis. Graph shows percent HT-I 080 cell death (Sytox green+ cells) 18 hours (white bars) or 24 hours (shaded bars) after the indicated treatments. Pre-treatment with erastin for 4 hours is indicated as '-' or'+'. Note that erastin-pre-treatment does not induce cell death on its own ('No treat'), but sensitizes to both continued erastin treatment ('Erastin'), and the combination of aMSH-PEG-C' dots (15 μM) and amino acid starvation ('AA-st+ aMSH'), as pre-treated cultures ('+') undergo more cell death at 18 and 24 hours. Bars indicate mean+/-standard deviation. N=5 per group. Each replicate is from one biological experiment, quantified with five independent fields of view. Thus, Bradbury teaches that erastin when used in a pretreatment combination therapy induces (i.e., activates) cell death more (See Fig. 7J description).
Furthermore, Bradbury teaches the induction of cell death in nutrient-deprived cancer cells comprising administering a composition comprising nanoparticles for accumulation at sufficiently high concentration in tumor tissue to induce ferroptosis (e.g. ferroptotic cell death involving iron-dependent necrosis or reactive oxygen species-dependent necrosis) (Abstract; [0022]; see entire document). Bradbury teaches the nanoparticles comprise ultrasmall nanoparticles (e.g., C dot, e.g., C dot) [0023]. Furthermore, Bradbury teaches a composition comprising nanoparticles (e.g., ultrasmall nanoparticles, e.g., C dot, e.g., C dot) for use in a method of treating a subject, wherein the treating comprises depriving a tumor tissue (e.g., prostate tissue) of the subject of hormones, e.g., chemical castration; and delivering the composition to the tumor tissue of the subject for accumulation at sufficiently high concentration (e.g., greater than 1 μM, e.g., greater than 15 μM, e.g., greater than 60 μM) in tumor tissue), wherein the nanoparticles are C dots or C dots) sensitive to the induction of ferroptosis) to induce ferroptosis [0038]. Moreover, the tumor can be deprived of hormones and sufficiently high concentrations of nanoparticles administered to the tumor can induce and/or even enhance a ferroptotic cell death program relative to tumors not exposed to hormonal or inhibitor treatments [0191], wherein a method of combinational treatment of a subject, the method comprising: depriving a tumor tissue (e.g., prostate cancer tissue) of hormones; and administering nanoparticles for accumulation at sufficiently high in the tumor tissue to induce ferroptosis (claims 16, 17).
Accordingly, the subject matter of claims 1-3, 7 and 9-20 are anticipated by the disclosure of Bradbury (WO2016196201).
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) 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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-4, 6, 7, 9-20 and 57 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bradbury et al (WO2016196201, cited in IDS filed 1/13/2025) [Bradbury] in view of Hawkins et al (US2017/0015660) [Hawkins] and Murga et al (Synergistic Co-Targeting of Prostate-Specific Membrane Antigen and Androgen Receptor in Prostate Cancer, The Prostate p.242, 2015) [Murga].
The teachings of Bradbury et al (WO201619620) regarding claims 1, 2, 7 and 9-20 are described above.
Bradbury differs from the claims in that the documents does not teach the first agent comprises enzalutamide (claim 57); administering the first agent to the subject of a daily basis (claim 3); the first agent comprises an androgen inhibitor and wherein the androgen inhibitor causes increased expression of PSMA by prostate cancer (claim 4); The method of claim 4, wherein the increased expression of PSMA by the prostate cancer cells results in enhanced ferroptotic induction by the second agent (claim 6);
Regarding claim 57,
Hawkins teaches methods for treating a condition by administering to the subject a therapeutically-effective amount of one or more compounds of the present teachings and one or more additional pharmaceutically active compounds, wherein the compounds are useful in the treatment of cancer, e.g., prostate cancer ([0140-0145].Hawkins teaches erastin compound, wherein erastin is a ferroptosis inducing compound/agent ([0019]; [0038, Fig.1; [0047, Fig. 10; [0093-0094; erastin structure); [0102-0103]; [0198], Table 1; See entire document).
Hawkins teaches the pharmaceutical agents which make up the combination therapy disclosed herein are optionally a combined dosage form or in separate dosage forms intended for substantially simultaneous administration. The pharmaceutical agents that make up the combination therapy are optionally also administered sequentially, with either agent being administered by a regimen calling for two-step administration. The two-step administration regimen optionally calls for sequential administration of the active agents or spaced-apart administration of the separate active agents. The time between the multiple administration steps ranges from a few minutes to several hours, depending upon the properties of each pharmaceutical agent, such as potency, solubility, bioavailability, plasma half-life and kinetic profile of the pharmaceutical agent [0150].
As a whole, Bradbury teaches erastin pretreatment by itself does not induce cell death (“no treatment”), but pretreated cultures (“+”) undergo more cell death at 18 and 24 hours, so sequential elastin treatment (“erastin”) and α-MSH-PEG-C′dot (15 μM) and the combination of amino acid starvation (“AA-st+αMSH”) [0095]; Fig. 7j). Moreover, Bradbury teaches that erastin when used in a pretreatment combination therapy induces (i.e., activates) cell death more (See Fig. 7J description). Bradbury teaches a method of combinational treatment of a subject, the method comprising: depriving a tumor tissue (e.g., prostate cancer tissue) of hormones; and administering nanoparticles (i.e., second agent: wherein the second agent comprises a ferroptosis-inducing nanoparticle with a PSMA-targeting ligand.) for accumulation at sufficiently high in the tumor tissue to induce ferroptosis (Abstract; [0021]; [0022]; [0027]; claim 16; See entire document).
Hawkins teaches erastin is a ferroptosis inducing agent [0019
In particular, Hawkins teaches erastin in combination with enzalutamide [0159].
Thus, it would have been prima facie obvious to one of ordinary skill in the art to modify the teachings of Bradbury to further comprises erastin in combination with enzalutamide (claim 57) together with the ferroptosis-inducing nanoparticle (a-MSHPEG-C' dots) to provide a combination treatment comprising erastin and enzalutamide having a reasonable expectation that the combination of erastin and enzalutamide would necessarily provide an enhanced therapeutic effect towards treating cancer, e.g. prostate cancer, in view of the teachings of Bradbury and Hawkins as a whole.
Regarding claims 3 and 4,
Murga teaches PSMA expression increased progressively over 3 weeks with enzalutamide (Abstract; See entire document). Murga teaches PSMA expression increased with continued treatment over three weeks and then rapidly returned to baseline upon removal of enzalutamide (right col., 2nd full para., See Fig.3: LNCaP cells: prostate cancer cells; See entire document). Thus, it would have been prima facie obvious to one of ordinary skill in the art that enzalutamide (androgen inhibitor) causes increased expression of PSMA by prostate cancer (claim 4).
Hawkins teaches that the time between the multiple administration steps ranges from a few minutes to several hours, depending upon the properties of each pharmaceutical agent, such as potency, solubility, bioavailability, plasma half-life and kinetic profile of the pharmaceutical agent [0150].
In view of Hawkins, one of ordinary skill in the art would have recognized that the time of administration between the first and second active agent is dependent on the properties of each active agent such as potency, solubility, bioavailability, plasma half-life and kinetic profile of the pharmaceutical agent [0150]. Thus, it would have been obvious to administer daily to maintain the therapeutic levels of the first agent: enzalutamide, in the body.
Based on Murga, it would be obvious to administer in a continuous fashion over three weeks to maintain increased expression of PSMA and thus enable selectivity of silica nanoparticles for prostate cancer cells. One of ordinary skill in the art would have recognized that a repeat administration inclusive of daily (i.e. continuous treatment) could maintain increased PSMA expression levels.
Accordingly, daily enzalutamide administration would be expected to improve the targeting efficacy of the silica nanoparticles as taught by Bradbury.
Therefore, it would be obvious to deliver enzalutamide (first agent) as an initial dose and then continue to deliver enzalutamide on ‘a daily basis’ to maintain and/or adjust the levels of PSMA. One skilled in the art would have been motivated to do so because daily administration of enzalutamide would be expected to enhance the silica nanoparticle selectivity to prostate cancer cells having a reasonable expectation of success (claim 3).
Regarding claim 6,
Furthermore, the combination treatment as taught by Bradbury, Hawkins and Murga, as a whole is chemically indistinquishable from the claimed composition, so that it would necessarily follow that the increased expression of PSMA by the prostate cancer cells produced by enzalutamide would result in enhanced ferroptotic induction by the ferroptosis-inducing nanoparticle (a-MSHPEG-C' dots) (second agent). This property would be the natural result of the combination of the prior art elements, i.e., "when the limitation at issue is the 'natural result' of the combination of prior art elements." PAR Pharm., Inc. v. TWI Pharms., Inc., 773 F.3d 1186, 1195 (Fed. Cir. 2014) (quoting In re Oelrich, 666 F.2d 578,581 (CCPA 1981)).
All the claimed elements herein are known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) 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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 2, 5, 7 and 9-20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bradbury et al (WO2016196201, cited in IDS filed 1/13/2025) [Bradbury] in view of Pauliah et al (US2015/0182118) [Pauliah].
The teachings of Bradbury et al (WO201619620) regarding claims 1, 2, 7 and 9-20 are described above.
Bradbury differs from the claims in that the documents does not teach: wherein the second agent comprises a ferroptosis-inducing nanoparticle with a PSMA-targeting ligand (claim 5)
However, Pauliah cures the deficiency.
Regarding claim 5,
Pauliah teaches probe nanoparticles, wherein nanoparticles have silica architecture and a dye-rich core, wherein a cellular abnormality is prostate cancer [0015-0019]. Pauliah teaches the silica nanoparticles (C dot) surface modified with multiple cancer directed ligands [0123].
Pauliah teaches a well-established cell surface antigen expressed by all prostate cancers, which can enhance tumor detection and localization of residual disease is PSMA, whose expression levels progressively increase in more poorly differentiated, metastatic and hormone-refractory cancers. The J591 mAb is reactive to a distinct extracellular epitope of PSMA, and has been clinically validated for use in tumor-targeted cancer detection and treatment. Another attractive and clinically-validated surface target for imaging prostate cancer is the gastrin-releasing peptide receptor (GRPr). GRPr overexpression has been observed in several malignant tumor types, but most consistently in prostate cancer. Furthermore, targeting of PSMA and GRPr is likely to be complementary, since PSMA is negatively regulated by androgen signaling whereas GRPr expression is increased by androgen signaling [0123].
Thus, it would have been prima facie obvious to one of ordinary skill in the art to modify the teachings of Bradbury to further comprises the ligand called J591 mAb that is taught by Pauliah as a ligand for silica nanoparticles (c dot), to react with (i.e., target; detect) PSMA. Moreover, one skilled in the art would have recognized that increased expression of PSMA produced by enzalutamide would provide motivation to attach J591 mAb ligand to silica nanoparticles (C dot) having a reasonable expectation that by attaching the ligand would necessarily selectively enhance the targeting of the silica nanoparticles to prostate cancer cells that would provide an improved (i.e., more targeted toward cancer cells) method of combination therapy to treat patient suffering from prostate cancer in contrast to using silica nanoparticles without a targeting ligand, e.g., J591 mAb, having a reasonable expectation of success.
All the claimed elements herein are known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Conclusions
No claim is allowed.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Thurman Wheeler whose telephone number is (571)-270-1307. The examiner can normally be reached Monday-Friday 11:00am-5:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on 571-272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/T.W./ Examiner, Art Unit 1619
/SARAH ALAWADI/ Primary Examiner, Art Unit 1619
Prosecution Insights