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 .
DETAILED ACTION
Response to Election/Restriction filed October 23, 2025 is acknowledged. Claims 1-17, 19-21 are pending in the current application.
Election/Restrictions
Applicant elected without traverse Formula III (PDZ1i which decreases MDA-9 activity via binding) from List I, paclitaxel from List II and prostate cancer from List III in the response filed October 23, 2025.
The restriction is deemed proper and is made FINAL in this office action. Claims 6-7, 11-13 are withdrawn as being drawn to a non-elected species/invention. Claims 1-5, 8-10, 14-17, 19-21 examined on the merits of this office action.
Claim Objections
Claim 1 is objected to for the following informality: the acronym MDA-9 should be spelled out in its first instance. For example, “Melanoma Differentiation Associated Gene-9 (MDA-9)”.
Claim 20 is objected to for the following informality: the acronym MDR1 should be spelled out in its first instance. For example, “Multidrug Resistance Mutation 1 (MDR1)”.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
It is noted that Applicants have not filed an information disclosure statement
under § 1.97(c). Applicant is reminded of 37 CFR § 1.56, which details Applicants duty to disclose all
information known to be material to patentability.
Claim Rejections - 35 USC § 112, first paragraph
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 1-5, 8-10, 14-17, 19-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating specific cancer types including prostate cancer with specific MDA-9 inhibitors and anti-cancer agents, does not reasonably provide enablement for treating/preventing (Applicants defined treating as prevention, paragraph 0186) of any cancer type with any MDA-9 inhibitor and anti-cancer agent encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To comply with the enablement requirements of 35 U.S.C. §112, first paragraph, a specification must adequately teach how to make and how to use a claimed invention throughout its scope, without undue experimentation. Plant Genetic Systems N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003). There are a variety of factors which may be considered in determining whether a disclosure would require undue experimentation. These factors include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The Nature of the Invention/ The breadth of the claims
The claims are drawn to “A method of treating cancer in a subject in need thereof, comprising administering to the subject a combined effective amount of (a) an agent that inhibits MDA-9, and (b) an anti- cancer agent, wherein the anti-cancer agent is a mitotic inhibitor or a histone deacetylase (HD AC) inhibitor” (see claim 1). Claim 6 further claims wherein the MDA-9 inhibitor is PDZ1i and claim 10 claims wherein the anticancer agent is taxol (paclitaxel).
The claims are extremely broad in that they encompass any compound or construct that inhibits MDA-9 and any anti-cancer drug across all cancers and also prevention of cancer. The specification enables only RNA based inhibition and one small molecule species (PDZ1i) in prostate cancer models. Furthermore, success of different inhibitor classes or drug combinations is not predictable because MDA-9 participates in multiple protein interactions and signaling contexts that vary among tissues and malignancies. Furthermore, claim 1 claims a “combined effective amount” and claim 2 claims a “synergistic amount”. There is no guidance or dosage ranges, data or selection criteria that would allow a skilled artisan to identify effective or synergistic amounts of the vast array of inhibitors, drugs and cancer types encompassed by the claims.
The State of the Prior Art
At the time of filing, MDA-9s role in cancer progression was emerging, but validate pharmacologic inhibitors were scare. The art does not provide routine methods to identify potent, selective PDZ domain inhibitors or to predict combination efficacy with diverse drugs. Yu (Computational and Structural Biotechnology Journal Volume 17, 2019, Pages 136-141). Yu teaches “Multiple studies demonstrate the key role of MDA-9/Syntenin in metastasis of various cancer cells. The expression level of MDA-9/Syntenin was found to be much higher in metastatic cell lines as compared with non-metastatic cancer-cell lines” (see section 4). Yu also states “Targeting of pharmaceuticals to MDA-9/Syntenin PDZ domains, however, has not been widely successfully developed. Because natural PDZ peptides binding interactions are often weak and promiscuous, so it is very challenging to develop pharmaceutical MDA-9/Syntenin PDZ inhibitors”. Thus, the field of treating/preventing cancer, and in particular with MDA-9 inhibitors is considered unpredictable.
The Predictability or Unpredictability of the Art/ The Relative Skill of Those in the Art
The prior art pertaining to the preventing/treating cancer broadly is non-existent (i.e. with one type of compound or combination of two compounds). The predictability in the art is low. Inhibiting one protein can have distinct effects depending on tumor genotype, pathway redundancy, and microenvironment. While RNAi effects on MDA-9 expression are predictable, pharmacologic inhibition across compound classes and tumor types is not. A skilled artisan could perform RNA knock down and xenograft studies but would not know how to design novel inhibitors or extend efficacy to unrelate cancers without extensive screening. The specification provides no structure activity pharmacological guidance to assist such efforts. Furthermore, determining “effective” or “synergistic” doses for all combinations would require extensive screening.
Amount of Guidance/ The Presence or Absence of Working Examples
Guidance is adequate only for reproducing the disclosed shMDA-9 constructs and administering PDZi (Formula III) in prostate cancer models (see Examples 1-9). No functional data or dosing ranges are provided for other inhibitor types encompassed by the claims. No general screening protocol is described that would predict which combinations with other anti-cancer drugs would succeed. Applicants reduce to practice RNA-based inhibition and PDZ1i inhibition in DU-145, ARCap-M and PC3-ML PCSC cells (Figures 5 and 9, for example). Applicants do not show prevention or using different inhibitors, different drug classes or other tumor types encompassed by claim.
The Quantity of Experimentation Necessary
To practice the full scope of the invention, one would need to design or identify numerous additional inhibitor classes, optimize potency, stability and delivery; test hundreds of possible drug combinations (if not more); show prevention; and validate efficacy in each of the claimed cancer types. This would require extensive, time consuming and unpredictable experimentation well beyond what is considered routine. Furthermore, identifying effective and synergistic amounts across the full scope would require numerous in vitro and in vivo dose response studies and amounting to undue experimentation.
Therefore, in view of the Wands factors, the claims appear to require undue experimentation to use the full scope of the claimed invention.
Claim Rejections - 35 USC § 112, first paragraph
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 1-5, 8-10, 14-17, 19-21are 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.
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.
Scope of the claims
The claims are drawn broadly to a method of treating cancer comprising administering an MDA-9 inhibitor which encompasses any compound or construct capable of inhibiting or reducing MDA-9 expression or activity (including small molecules, antibodies, peptides, aptamers, antisense oligonucleotides, siRNA and shRNA) and an anti cancer drug (which encompasses any chemo agent, targeting agent or biologic) for treating/preventing any cancer type including prostate, breast, lung, melanoma, neuroblastoma, and drug resistant tumors. Thus, the claims define a vast genus of inhibitor/drug combinations and therapeutic indications, requiring support showing the inventors were in possession of the entire genus or a representative number of species commensurate with the breadth of the claims.
Actual Reduction to Practice
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. 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.
Applicant’s reduce to practice the following:MDA-9 knockdown in prostate cancer cells and stem cell populations, RNA based inhibition (shMDA-9/siRNA); small molecule PDZ domain inhibitor (PDZ1i); PSSC xenografts and combination with docetaxel and one instance with Trichostatin A (see Figures 5 and 9). No examples show other small molecule scaffolds or antibodies; combination with other anti-cancer drug classes, treatment or prevention of other cancer types. Thus, the specification establishes possession of RNA based and PDZi based inhibition in prostate cancer, not the broader genus claimed.
One of ordinary skill in the art would not consider the examples provided in the instant specification to be representative of the full scope of the claimed genus.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
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 thereof.
The specification provides a single structural formula (formula III, PDZ1i); a mention that MDA-9 inhibitors block the PDZ domain of MDA-9 and functional data showing PDZ1i reduces MDA-9 signaling. However, the disclosure lacks any description of additional representative species, sequence data or structural motifs defining the genus of MDA-9 inhibitors. NO structural or sequence based boundaries are disclosed that would let a skill artisan envisage the genus beyond PDZ1i and RNA constructs.
Physical and/or chemical properties:
The specification does not describe physical or chemical properties of the MDA-9 inhibitors other than providing the chemical structure of PDZ1i. There are no weight ranges, solubility data, binding constants, stability, sequence analysis or formulation details for PDZ1i or any other inhibitor class. Without such descriptive properties, one cannot determine whether additional inhibitors would share a common structural or physicochemical attributes correlating with the claimed function.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification defines MDA-9 inhibitors functionally, as agents that reduce MDA-9 expression or activity. While functional descriptions may satisfy written description when a clear structure-function correlation is established, the disclosure here provides no general correlation beyond PDZ1i and shMDA-9 constructs. The only demonstrated structure function relationships are RNAi constructs and PDZ1i. The specification does not provide evidence or reasoning showing that structurally unrelated inhibitors (e.g., antibodies, peptides, or different small molecule chemotypes) would necessarily interact with MDA-9 in the same manner or achieve equivalent functional outcomes across all cancers. Absent such correlation, functional language alone cannot demonstrate possession of the entire genus.
Without the structure/function correlation, it is impossible to predict, based on the specification what peptide would have the required function.
Method of Making
The specification discloses how to make shMDA-9 constructs and references PDZ1i as a known compound but does not disclose any general method of making or identifying additional MDA-9 inhibitors. There are no synthesis routes, combinatorial screening methods, binding assays or rational design strategies for novel compounds. A skilled artisan could reproduce PDZ1i but could not, from the disclosure, make or obtain other inhibitors encompassed by the claims that would have the desired functional properties. Therefore, the method of making requirement is satisfied only for the exemplified species not the claimed genus..
Thus, given the breadth of the claims, lack of structure in general, the lack of guidance in the specification regarding a structure/function correlation, it is not possible for one of ordinary skill in the art to determine what protein encompassed within the claimed genus would have the desired functional property.
Conclusion
In conclusion, the specification fails to provide adequate written description support for the broad genus MDA-9 inhibitors and anti cancer agents have the required properties of treating cancer. The disclosure lacks sufficient structure function correlation, physical/chemical data and examples that demonstrate possession of the full scope of the claimed genus. Accordingly, only specific peptides reduced to practice, satisfies the written description requirements of 35 U.S.C. 112, first paragraph.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 8-10, 14-17 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Fisher (WO2018089967 A1).
Fisher teaches of a method of inhibiting MDA-9 protein activity and treating cancer comprising administering an effective amount of a PDZ1 domain binder (see claims 37 and 43). Fisher further teaches wherein the inhibitor is PDZ1i (see claim 35) which is identical to the inhibitor of claim 5 and falls within the scope of instant claims 3-4. Fisher further teaches administering an anti-cancer agent (see claim 49, see also claim Figure 41). In particular, Fisher teaches the combination of PDZ1i and 5-FU (an anti-cancer agent that is a mitotic inhibitor, see Figure 41). Regarding claims 1-2, Fisher teaches administering combined synergistic amounts (see paragraphs 0555-0557).
Regarding claim 8, Fisher teaches the combination of PDZ1i and 5-FU (an anti-cancer agent that is anti-microtubule agent, see Figure 41). Regarding claims 9-10, Fisher teaches wherein the anticancer agent is taxol (see paragraph 0531) which is paclitaxel. Regarding claim 14, Fisher teaches co-administration (see paragraph 0214). Regarding the limitation of “wherein administration of the agent that inhibits MDA-9 and the anti-cancer agent increase apoptotic cell death in cancer stem cells in the subject as compared to a subject administered either agent alone” in claim 15, this is a result oriented effect that necessarily would occur given the method of Fisher is identical of the instant claims (same patient population, same drugs, same amounts) and based on the inherent properties of the agents being administered together. Regarding claims 16-17, Fisher teaches treatment of pancreatic cancer (see figure 41) and also prostate cancer (see Figure 19A-19F for example, also see paragraph 0205).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5, 8-10, 14-17, 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Fisher (WO2018089967 A1) in view of Williamson (US20040203060 A1).
Fisher teaches of a method of inhibiting MDA-9 protein activity and treating cancer comprising administering an effective amount of a PDZ1 domain binder (see claims 37 and 43). Fisher further teaches wherein the inhibitor is PDZ1i (see claim 35) which is identical to the inhibitor of claim 5 and falls within the scope of instant claims 3-4. Fisher further teaches administering an anti-cancer agent (see claim 49, see also claim Figure 41). In particular, Fisher teaches the combination of PDZ1i and 5-FU (an anti-cancer agent that is a mitotic inhibitor, see Figure 41). Regarding claims 1-2, Fisher teaches administering combined synergistic amounts (see paragraphs 0555-0557).
Regarding claim 8, Fisher teaches the combination of PDZ1i and 5-FU (an anti-cancer agent that is anti-microtubule agent, see Figure 41). Regarding claims 9-10, Fisher teaches wherein the anticancer agent is taxol (see paragraph 0531) which is paclitaxel. Regarding claim 14, Fisher teaches co-administration (see paragraph 0214). Regarding the limitation of “wherein administration of the agent that inhibits MDA-9 and the anti-cancer agent increase apoptotic cell death in cancer stem cells in the subject as compared to a subject administered either agent alone” in claim 15, this is a result oriented effect that necessarily would occur given the method of Fisher is identical of the instant claims (same patient population, same drugs, same amounts) and based on the inherent properties of the agents being administered together. Regarding claims 16-17, Fisher teaches treatment of pancreatic cancer (see figure 41) and also prostate cancer (see Figure 19A-19F for example, also see paragraph 0205).
Fisher is silent to wherein the cancer is chemo resistant or the cancer is recurrent.
However, Fisher does teach that “A clinical study also found that elevated expression of MDA-9 correlated with increased metastasis and tumor recurrence in breast cancer patients” (see paragraph 0643).
Williamson teaches that Increased expression of MDA-9 is associated with drug resistance of certain cells (e.g., cancer cells). Williamson teaches that “the invention also features a method for treating a drug resistant tumor in a patient, the method comprising administering to said subject an amount of a MDA-9 antagonist effective to reduce drug resistance of said tumor in the patient. In another aspect, the invention features the use of an inhibitor of MDA-9 expression, or pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity, for the manufacture of a medicament for the treatment of a drug resistant tumor in a patient” (see paragraph 0041).
It would have been obvious before the effective filing date of the claimed invention to combine Fishers MDA-9 inhibitor/Chemo agent therapy with Williamsons teaching that MDA-9 inhibition reduces drug resistance and recurrence. One of ordinary skill in the art would have been motivated to do so to enhance responsiveness to chemotherapy and prevent relapse in patients that are chemo resistant.
Furthermore, this combination is supported by a predictable result: both references teach that inhibition or suppression of MDA-9 activity in combination with chemotherapy for treatment of cancer and Williamson teaches MDA-9 improves chemotherapeutic sensitivity by modulating STAT3/MDR1 dependent pathways. A person of ordinary skill would therefore have had a reasonable expectation of success in using Fishers combination to treat chemo resistant or recurrent cancers as described by Williams (see KSR Int’l v. Teleflex, 550 U.S. 398, 2007; MPEP2143).
Regarding treating MDR1 mediated chemoresistance (instant claim 20), it would have been obvious to try treating MDR1 mediated chemoresistance using the inhibitor of Fisher, in view of Williamson’s teaching that inhibition of MDA-9 reduces drug resistance potentially through modulation of MDR1 pathways (paragraph 0203). Because both references identify MDA-9 as a molecular target influencing chemotherapeutic response, a person of ordinary skill would have recognized that applying Fishers therapy to the MDR1 mediated resistance represented a predictable solution with a reasonable expectation of success in improving drug sensitivity in any chemo resistant state (KSR int’l co. v. Teleflex inc, 550 U.S. 398, 2007, MPEP 2143).
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 1-5, 8-10, 14-17, 19-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-50 of U.S. Patent No. 1108325 in view of Fisher (WO2018089967 A1) in view of Williamson (US20040203060 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of treating cancer in a subject in need thereof, comprising administering to the subject a combined effective amount of (a) an agent that inhibits MDA-9, and (b) an anti- cancer agent, wherein the anti-cancer agent is a mitotic inhibitor or a histone deacetylase (HD AC) inhibitor” (claim 1). THe instant application further claims PDZ1i (claim 6); taxane (claim 9); paclitaxel (claim 10); prostate cancer, breast cancer, gastric cancer, lung cancer, brain cancer, colorectal cancer, pancreatic cancer, melanoma, and neuroblastoma (claim 16); prostate cancer (claim 17); chemo resistant cancer (Claim 19); MDR1 mediated chemoresistance (Claim 20) and recurrence (claim 21).
US Patent No. 11008325 claims “A method of treating cancer in a subject in need thereof, said method comprising administering to said subject an effective amount of a PDZ domain binder, wherein the PDZ1 domain binder is a compound of claim 1” (claim 29). US Patent No. 11008325 further claims wherein the binder is PDZ1i (see claim 24); further administering an anti-cancer agent (Claim 32);prostate cancer treatment (Claim 34). US Patent No. 11008325 is silent to taxol as the cancer agent, co-administration (even though its implied), treatment of Chemo resistant or recurrent cancer.
However, Fisher teaches of a method of inhibiting MDA-9 protein activity and treating cancer comprising administering an effective amount of a PDZ1 domain binder (see claims 37 and 43). Fisher further teaches wherein the inhibitor is PDZ1i (see claim 35) which is identical to the inhibitor of claim 5. Fisher further teaches administering an anti-cancer agent (see claim 49, see also claim Figure 41). In particular, Fisher teaches the combination of PDZ1i and 5-FU (an anti-cancer agent that is a mitotic inhibitor, see Figure 41). Fisher teaches administering combined synergistic amounts (see paragraphs 0555-0557).
Fisher teaches wherein the anticancer agent is taxol (see paragraph 0531) which is paclitaxel. Fisher teaches co-administration (see paragraph 0214). Fisher teaches treatment of pancreatic cancer (see figure 41) and also prostate cancer (see Figure 19A-19F for example, also see paragraph 0205).
Fisher does teach that “A clinical study also found that elevated expression of MDA-9 correlated with increased metastasis and tumor recurrence in breast cancer patients” (see paragraph 0643).
Williamson teaches that Increased expression of MDA-9 is associated with drug resistance of certain cells (e.g., cancer cells). Williamson teaches that “the invention also features a method for treating a drug resistant tumor in a patient, the method comprising administering to said subject an amount of a MDA-9 antagonist effective to reduce drug resistance of said tumor in the patient. In another aspect, the invention features the use of an inhibitor of MDA-9 expression, or pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity, for the manufacture of a medicament for the treatment of a drug resistant tumor in a patient” (see paragraph 0041).
It would have been obvious before the effective filing date of the claimed invention to combine US Patent No. ‘325 with the teachings of the MDA-9 inhibitor/Chemo agent therapy of Fisher. One of ordinary skill in the art would have been motivated to do so to given that both are teaching treating the same cancer types with an agent that inhibits MDA-9 and a chemotherapeutic agent.
Furthermore, it would have been obvious before the effective filing date of the claimed invention to combine US Patent No. ‘325 with the MDA-9 inhibitor/Chemo agent therapy of Fisher with Williamsons teaching that MDA-9 inhibition reduces drug resistance and recurrence. One of ordinary skill in the art would have been motivated to do so to enhance responsiveness to chemotherapy and prevent relapse in patients that are chemo resistant.
Furthermore, this combination is supported by a predictable result: both references teach that inhibition or suppression of MDA-9 activity in combination with chemotherapy for treatment of cancer and Williamson teaches MDA-9 improves chemotherapeutic sensitivity by modulating STAT3/MDR1 dependent pathways. A person of ordinary skill would therefore have had a reasonable expectation of success in using Fishers combination to treat chemo resistant or recurrent cancers as described by Williams (see KSR Int’l v. Teleflex, 550 U.S. 398, 2007; MPEP2143).
Regarding treating MDR1 mediated chemoresistance (instant claim 20), it would have been obvious to try treating MDR1 mediated chemoresistance using the inhibitor of US Patent No. ‘325 in view of Fisher and Williamson’s teaching that inhibition of MDA-9 reduces drug resistance potentially through modulation of MDR1 pathways (paragraph 0203). Because both references (including US Patent No. ‘325) identify MDA-9 as a molecular target influencing chemotherapeutic response, a person of ordinary skill would have recognized that applying US Patent No. ‘325s therapy to the MDR1 mediated resistance represented a predictable solution with a reasonable expectation of success in improving drug sensitivity in any chemo resistant state (KSR int’l co. v. Teleflex inc, 550 U.S. 398, 2007, MPEP 2143).
Regarding the limitation of “wherein administration of the agent that inhibits MDA-9 and the anti-cancer agent increase apoptotic cell death in cancer stem cells in the subject as compared to a subject administered either agent alone”, this is a result oriented effect that necessarily would occur given the method of US Patent. No. 325 in view of Fisher is identical of the instant claims (same patient population, same drugs, same amounts) and based on the inherent properties of the agents being administered together.
Claims 1-5, 8-10, 14-17, 19-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 17-25 of U.S. Patent No. 11891399 B2 in view of Fisher (WO2018089967 A1) in view of Williamson (US20040203060 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of treating cancer in a subject in need thereof, comprising administering to the subject a combined effective amount of (a) an agent that inhibits MDA-9, and (b) an anti- cancer agent, wherein the anti-cancer agent is a mitotic inhibitor or a histone deacetylase (HD AC) inhibitor” (claim 1). The instant application further claims PDZ1i (claim 6); taxane (claim 9); paclitaxel (claim 10); prostate cancer, breast cancer, gastric cancer, lung cancer, brain cancer, colorectal cancer, pancreatic cancer, melanoma, and neuroblastoma (claim 16); prostate cancer (claim 17); chemo resistant cancer (Claim 19); MDR1 mediated chemoresistance (Claim 20) and recurrence (claim 21).
US Patent No. 111891399 B2 claims “A method of treating cancer in a subject in need thereof, said method comprising administering to said subject an effective amount of a PDZ domain binder, wherein the PDZ1 domain binder is a compound of claim 1” (claim 19). US Patent No. 11891399 further claims wherein the binder encompasses PDZ1i (see claims 1, 12); further administering an anti-cancer agent (Claim 32);prostate cancer treatment (Claim 21). U.S. Patent No. 11891399 is silent to taxol as the cancer agent, co-administration (even though its implied), treatment of Chemo resistant or recurrent cancer.
However, Fisher teaches of a method of inhibiting MDA-9 protein activity and treating cancer comprising administering an effective amount of a PDZ1 domain binder (see claims 37 and 43). Fisher further teaches wherein the inhibitor is PDZ1i (see claim 35) which is identical to the inhibitor of claim 5. Fisher further teaches administering an anti-cancer agent (see claim 49, see also claim Figure 41). In particular, Fisher teaches the combination of PDZ1i and 5-FU (an anti-cancer agent that is a mitotic inhibitor, see Figure 41). Fisher teaches administering combined synergistic amounts (see paragraphs 0555-0557).
Fisher teaches wherein the anticancer agent is taxol (see paragraph 0531) which is paclitaxel. Fisher teaches co-administration (see paragraph 0214). Fisher teaches treatment of pancreatic cancer (see figure 41) and also prostate cancer (see Figure 19A-19F for example, also see paragraph 0205).
Fisher does teach that “A clinical study also found that elevated expression of MDA-9 correlated with increased metastasis and tumor recurrence in breast cancer patients” (see paragraph 0643).
Williamson teaches that Increased expression of MDA-9 is associated with drug resistance of certain cells (e.g., cancer cells). Williamson teaches that “the invention also features a method for treating a drug resistant tumor in a patient, the method comprising administering to said subject an amount of a MDA-9 antagonist effective to reduce drug resistance of said tumor in the patient. In another aspect, the invention features the use of an inhibitor of MDA-9 expression, or pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity, for the manufacture of a medicament for the treatment of a drug resistant tumor in a patient” (see paragraph 0041).
It would have been obvious before the effective filing date of the claimed invention to combine US Patent No. ‘399 with the teachings of the MDA-9 inhibitor/Chemo agent therapy of Fisher. One of ordinary skill in the art would have been motivated to do so to given that both are teaching treating the same cancer types with an agent that inhibits MDA-9 and a chemotherapeutic agent.
Furthermore, it would have been obvious before the effective filing date of the claimed invention to combine US Patent No. ‘399 with the MDA-9 inhibitor/Chemo agent therapy of Fisher with Williamsons teaching that MDA-9 inhibition reduces drug resistance and recurrence. One of ordinary skill in the art would have been motivated to do so to enhance responsiveness to chemotherapy and prevent relapse in patients that are chemo resistant.
Furthermore, this combination is supported by a predictable result: both references teach that inhibition or suppression of MDA-9 activity in combination with chemotherapy for treatment of cancer and Williamson teaches MDA-9 improves chemotherapeutic sensitivity by modulating STAT3/MDR1 dependent pathways. A person of ordinary skill would therefore have had a reasonable expectation of success in using Fishers combination to treat chemo resistant or recurrent cancers as described by Williams (see KSR Int’l v. Teleflex, 550 U.S. 398, 2007; MPEP2143).
Regarding treating MDR1 mediated chemoresistance (instant claim 20), it would have been obvious to try treating MDR1 mediated chemoresistance using the inhibitor of US Patent No. ‘399 in view of Fisher and Williamson’s teaching that inhibition of MDA-9 reduces drug resistance potentially through modulation of MDR1 pathways (paragraph 0203). Because both references (including US Patent No. ‘399) identify MDA-9 as a molecular target influencing chemotherapeutic response, a person of ordinary skill would have recognized that applying US Patent No. ‘399s therapy to the MDR1 mediated resistance represented a predictable solution with a reasonable expectation of success in improving drug sensitivity in any chemo resistant state (KSR int’l co. v. Teleflex inc, 550 U.S. 398, 2007, MPEP 2143).
Regarding the limitation of “wherein administration of the agent that inhibits MDA-9 and the anti-cancer agent increase apoptotic cell death in cancer stem cells in the subject as compared to a subject administered either agent alone”, this is a result oriented effect that necessarily would occur given the method of US Patent. No. 399 in view of Fisher is identical of the instant claims (same patient population, same drugs, same amounts) and based on the inherent properties of the agents being administered together.
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/ Examiner, Art Unit 1654