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 .
Claim of Priority
The provisional application does refer to the following terms and therefore does not have priority to the provisional application filing date: relapsed, refractory, Double-Hit, and Burkitt’s Lymphoma. As such, those claims that include these limitations do not have priority earlier than May 3, 2022, which is the filing date of the US PCT application US2022/072091.
Status of the Claims
Claims 1-20 are pending and examined.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Allowable Subject Matter
Claims 3, 4, 8, 15, and 18-20 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112
Claim 11 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Interpretation
The examiner interprets the term “including” preceding a list of cancers to be limited to those cancers. It is interpreted as extensive.
Claim Rejections - 35 USC § 112-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, 2, 5-7, 9, 10, 12-14, 16, and 17 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 hematologic malignancies, e.g., does not reasonably provide enablement for the treatment of all blood cancers i.e., all lymphomas and/or leukemias as well as refractory and relapsed AML and CML. 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, including treating those specific types of cancers claimed including those cells lines listed in Table 1 of the Specification including Mantle Cell Lymphoma, Double-Hit Lymphoma, Burkitt’s Lymphoma, Anaplastic Large Cell Lymphoma, Multiple Myeloma, ALL, CML, and AML.
In this regard, the application disclosure and claims have been compared per the factors indicated in the decision In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988) as to undue experimentation. The factors include 1) the nature of the invention; 2) the breadth of the claims; 3) the unpredictability of the art; 4) the amount of direction or guidance presented; 5) the presence or absence of working examples; 6) the quantity of experimentation necessary; 7) the state of the prior art; and, 8) the relative skill of those skilled in the art.
The relevant factors are addressed below on the basis of comparison of the disclosure, the claims and the state of the prior art in the assessment of undue experimentation.
The Breadth of the Claims
The presently claimed invention is directed to a method of treating any blood cancer, including those that are relapsed and/or refractory. The claims embrace a substantially broad and diverse group of cancers, including over 100 types of cancers, including myeloma, leukemia, and lymphoma. Yale Medicine explains: “With over 100 different types of blood cancers now recognized, it is important to have an accurate diagnosis prior to deciding on treatment,” says Dr. Huntington. This statement also insinuates that treatment is not the same for all cancers. See https://www.yalemedicine.org/conditions/blood-cancers -date accessed January 6, 2026.
The Nature of the Invention
The claimed invention is directed to the treatment of all blood cancers, including relapsed and refractory with a single potent compound that the state of the art recognizes as a potent alkylating agent with two active enantiomeric forms.
Level of Ordinary Skill in the Art:
The level of skill in the art is high, requiring an advanced degree in biochemistry and medicine.
The State of the Prior Art and Unpredictability in the Art
Enzmann, “What Are Blood Cancers and How Do We Beat Them?” November 19, 2021, https://missionbio.com/company/blog/what-are-blood-cancers/#:~:text=There%20is%20no%20single%20treatment,mechanisms%20underlying%20a%20patient%27s%20cancer -accessed January 6, 2026, teaches: “There is no single treatment for blood cancer. A patient’s treatment is determined by his or her specific diagnosis.”
As noted above, Yale Medicine explains: “With over 100 different types of blood cancers now recognized, it is important to have an accurate diagnosis prior to deciding on treatment,” says Dr. Huntington. This is interpreted to mean that treatment will not be the same for all types of blood cancers.
In other words, it is not likely that all blood cancers can be treated with the claimed agent.
Amount of direction provided by the inventor and existence of working examples:
The Specification evaluates the IC50 nM value for LP-284 (i.e., the claimed enantiomer) evaluated at 48 and 72 hours in the following cell lines: Mantle Cell Lymphoma, Double-Hit Lymphoma, Burkitt’s Lymphoma, Anaplastic Large Cell Lymphoma, Multiple Myeloma, ALL, CML, and AML.
The values range from 88 nM at 72 hours up to 2220 nM at 48 hours. Thus, the range is substantial. However, there is a level of sensitivity to the active agent for these cell lines. It is not clear that any cell line is relapsed or refractive.
As discussed above, the working examples in the specification provide a specific concentration in vitro will provides a sensitivity in a specific and esoteric group of blood cancers that are not shown to be refractory or relapsed cancers.
In light of such, it is clear that one of ordinary skill in the art would be faced with the impermissible burden of undue experimentation in order to execute the entire scope of the subject matter presently claimed, including analyzing which blood cancers of the more than 100 identified and their relapsed and refractory counterparts can be treated with the claimed agent at a dose and route of administration that is required. The basis for the present rejection is not simply that experimentation would be required, since it is clear from the state of the pharmaceutical and chemical arts that experimentation in this particular art is not at all uncommon, but that the level of experimentation required in order to practice this aspect of the invention in the absence of any enabling direction by Applicant would be undue. Please reference In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976), which states, "The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue."
Given the high degree of unpredictability noted and recognized in the art above coupled with the lack of working examples of demonstrating the capacity of the claimed combination of metabolites to treat and prevent all inflammatory conditions, the encompassed scope of the pending claims is determined to be not enabled. In the absence of any direction or guidance presented by Applicant as to how such a therapeutic objective could be achieved without necessitating an undue level of experimentation, the present disclosure is viewed as lacking an enabling disclosure of the entire scope of the presently claimed subject matter.
To obviate this rejection, the examiner proposes the following amendments to the claims:
Limit the claims to treatment of those cancer that the Specification and/or the state of the art in combination with the Specification supports. In other words, incorporate the limitations of claims 8 and 15 into the independent claims.
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.
Claim 1, 2, 12-14, 16, and 17 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Tobin et al., (WO2020051222) (published March 12, 2020).
Tobin teaches treating cancer with a compound that includes a racemic mixture showing the following:
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Tobin claims a mixture of these compounds. See prior art claim 2. This class of compounds is taught to treat myelocytic leukemia and other malignant cells. A person of ordinary skill in the art would immediately envisage treating myelocytic leukemia with the claimed compound or a composition comprising the same in light of the above. Administration can be by routes including IV, IM, and IP, among others. See p10, lines 18-21. Administration to a human is claimed. See prior art claim 17.
As such, claims 1, 2, 12-14, 16, and 17 are anticipated by the prior art.
Claim 1, 2, 7, 9, 11-14, 16, and 17 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by McMorris et al., (U.S. Pat. No. 7,655,695).
McMorris teaches acylfulvene analogs for treating cancer, including hematologic cancers. See Abstract. An enantiomer of the claimed compound is shown as an exemplified agent. See col. 4, lines 30-40. Cancers that can be treated include:
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See col. 6, lines 2-8. Further, AML and CML can also be treated. See col. 6, lines 14-15. Compounds claimed can be in optically active and racemic forms. See col. 7, line 6. Administration can be intravenously, orally, parenterally, and through other routes. See col. 12, lines 65-67. Further, the compounds can be co-administered with a chemotherapeutic agent, alkylating agent, anti-androgen, anti-estrogen, or other anti-cancer therapy. See col. 3, lines 35-44. One such drug listed is imatinib, which is a tyrosine kinase inhibitor. McMorris also states that the drugs are effective against multi-drug resistant cancers. See Abstract.
As such, claims 1, 2, 7, 9, 11-14, 16, and 17 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, 2, 5-7, 9, 11-14, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over McMorris et al., (U.S. Pat. No. 7,655,695), in view of Kathad et al., “Correlation of gene expression profile to identify tumors with extreme sensitivity to the alkylating agent LP184,” Abstract May 25, 2020 ASCO Annual Meeting, and in view of Gallatin (U.S. Pat. No. 9,492,449).
McMorris teaches acylfulvene analogs for treating cancer, including hematologic cancers. See Abstract. An enantiomer of the claimed compound is shown as an exemplified agent. See col. 4, lines 30-40. Cancers that can be treated include:
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See col. 6, lines 2-8. Further, AML and CML can also be treated. See col. 6, lines 14-15. Compounds claimed can be in optically active and racemic forms. See col. 7, line 6. Administration can be intravenously, orally, parenterally, and through other routes. See col. 12, lines 65-67. Further, the compounds can be coadministered with a chemotherapeutic agent, alkylating agent, anti-androgen, anti-estrogen, or other anti-cancer therapy. See col. 3, lines 35-44. One such drug listed is imatinib, which is a tyrosine kinase inhibitor. McMorris also states that the drugs are effective against multi-drug resistant cancers. See Abstract.
Kathad teaches LP184 is a next generation alkylating acylfulvene class prodrug. Kathad teaches LP184 is a next generation alkylating acylfulvene class prodrug. LP184 is a potent alkylating agent with nanomolar potency in a variety of solid tumors.
Gallatin teaches therapies for treating hematologic cancers including those that have relapsed and are refractory to chemotherapy including AML and ALL. See par. 1. Such treatment comprises administration of an alkylating agent. See prior art claim 14.
In view of Kathad and Gallatin, the claimed agent is known to be a next generation alkylating agent. Further, alkylating agents are taught to treat hematologic cancers including those that are relapsed and refractory to AML and ALL.
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 arrive at the claimed methods in view of McMorris, Kathad, and Gallatin. One would be motivated to do so because the claimed agent and/or an enantiomer thereof is taught to treat claimed forms of cancer. Further, if a cancer such as AML or ALL were to relapse, a standard treatment for relapse is the same drug that induced remission although a dosage may be increased. Even further, LP184 which is an enantiomer and is include in a racemic form of claimed API is taught to be a potent alkylating agent. Gallatin further teaches treating relapsed and refractory AML and ALL with a combination of drugs that includes an alkylating agent. As such, there is a reasonable and predictable expectation of success in treating the claimed subject populations with the claimed agents, including if they relapse because it is standard to use an alkylating agent to treat the same subject population during remission. As such, there is a reasonable and predictable expectation of success in administration of the claimed agents to the claimed subject population.
Claim(s) 1, 2, 5-7, 9, 11-14, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over McMorris et al., (U.S. Pat. No. 7,655,695), in view of https://cancer.ca/en/cancer-information/cancer-types/acute-myeloid-leukemia-aml/treatment/relapsed-or-refractory#:~:text=Chemotherapy%20is%20the%20main%20treatment,was%20longer%20than%20one%20year Canadian Cancer Society, “Treatments for relapsed or refractory acute myeloid leukemia,” February 2022, in view of Kathad et al., “Correlation of gene expression profile to identify tumors with extreme sensitivity to the alkylating agent LP184,” Abstract May 25, 2020 ASCO Annual Meeting, and in view of Gallatin (U.S. Pat. No. 9,492,449).
McMorris teaches acylfulvene analogs for treating cancer, including hematologic cancers. See Abstract. An enantiomer of the claimed compound is shown as an exemplified agent. See col. 4, lines 30-40. Cancers that can be treated include:
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See col. 6, lines 2-8. Further, AML and CML can also be treated. See col. 6, lines 14-15. Compounds claimed can be in optically active and racemic forms. See col. 7, line 6. Administration can be intravenously, orally, parenterally, and through other routes. See col. 12, lines 65-67. Further, the compounds can be coadministered with a chemotherapeutic agent, alkylating agent, anti-androgen, anti-estrogen, or other anti-cancer therapy. See col. 3, lines 35-44. One such drug listed is imatinib, which is a tyrosine kinase inhibitor. McMorris also states that the drugs are effective against multi-drug resistant cancers. See Abstract.
Canadian Cancer Society teaches that chemotherapy is the main treatment for relapsed and refractory AML and it may include repeating the same or a similar drug that was used to induce remission. Similar or higher doses can be used. In view of this understanding, the use of claimed drugs would also be used for a relapse.
Kathad teaches LP184 is a next generation alkylating acylfulvene class prodrug. Kathad teaches LP184 is a next generation alkylating acylfulvene class prodrug. LP184 is a potent alkylating agent with nanomolar potency in a variety of solid tumors.
Gallatin teaches therapies for treating hematologic cancers including those that have relapsed and are refractory to chemotherapy including AML and ALL. See par. 1. Such treatment comprises administration of an alkylating agent. See prior art claim 14.
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 arrive at the claimed methods in view of McMorris, Canadian Cancer Society, Kathad, and Gallatin. One would be motivated to do so because the claimed agent and/or an enantiomer thereof is taught to treat claimed forms of cancer. Further, if a cancer such as AML or ALL were to relapse, a standard treatment for relapse is the same drug that induced remission although a dosage may be increased. Even further, LP184 which is an enantiomer and include in a racemic form of claimed API is taught to be a potent alkylating agent. Gallatin further teaches treating relapsed and refractory AML and ALL with a combination of drugs that includes an alkylating agent. As such, there is a reasonable and predictable expectation of success in treating the claimed subject populations with the claimed agents, including if they relapse and/or have refractory cancers because it is standard to use an alkylating agent to treat the same subject and it is further standard to use a same drug that induced remission during a relapse. As such, there is a reasonable and predictable expectation of success in administration of the claimed agents to the claimed subject population.
As such, no claim is presently allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628