DETAILED ACTION
This office action is in response to the Applicant’s filing dated January 26th, 2026.
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 .
Priority
This application is a 371 of PCT/US2022/014109 filed on January 27th, 2022; which has a PRO of 63/142,841 filed on January 28th, 2021.
Status of Claims
Claims 1-2, 5, 10, 20-35 are pending in the instant application. Acknowledgement is made of Applicant’s remarks and amendments filed on January 26th, 2026. Acknowledgment is made of Applicant’s amendment of claims 23 and 33.
Election/Restrictions
Applicant’s election without traverse of MI-3454 shown below and sickle cell disease in the reply filed on January 26th, 2026 is acknowledged:
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Claims 5, 10 and 28-29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 26th, 2026.
A prior art search was conducted for the elected species.
No prior art was found.
Therefore, the Examiner expanded search to include the full scope of the claims. Claims 5, 10 and 28-29 are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on November 25th, 2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 1-2, 5, 10 and 20-35 will be examined herein.
Claim Rejections - 35 USC § 112(a)
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, 10 and 20-35 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 increasing human fetal (γ) and embryonic (ε) hemoglobin expression in human CD34+ erythroid cells with PTC-596 and MI-3454 in Example 3 on page 47 in vitro, does not reasonably provide enablement for treating ß-globinopathy in a subject with any compound that inhibits the activity of BMI1 or Mixed Lineage Leukemia (MLL) complex. 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. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
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 of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention and breadth of the claims
The invention relates to a method of treating a subject having or susceptible to ß-globinopathy comprising administering to the subject a therapeutically effective amount of a compound that inhibits the activity of BMI1 or Mixed Lineage Leukemia complex.
Instant claims 1-2, 5, 10 and 20-35 are directed to a method for treating ß-globinopathy in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound that inhibits the activity of BMI1 or Mixed Lineage Leukemia (MLL) complex. The language “a compound that inhibits the activity of BMI1 or Mixed Lineage Leukemia (MLL) complex” could be reasonably interpreted to encompass compounds still yet to be discovered. Thus, the claims are extremely broad with regards to the possible compounds that can be utilized.
2. The state and predictability of the art, and relative skill of those in the art
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
As illustrative of the state of the art, the examiner cites Wu et al (WO 2017/161002 A1), cited for evidentiary purposes only, teaches that MI-3454, referred to as Compound 85 (page 49), is a potent inhibitor of MENIN-MLL interaction with a top performing IC50 of <50nM (page 79, Table 2); including MLL1 (page 14, paragraph [0057]; page 90, claim 42), also known in the art as KMT2A. Barbarani et al (Frontiers in Genome Editing, (2020), 2571239), also cited for evidentiary purposes only, teaches that the definitive cure for β-globinopathy is Hematopoietic Stem Cell (HSC) transplantation, a treatment available only for the few patients who have an Human Leukocyte Antigen (HLA) matched donor. Despite intense efforts, the only drug of some efficacy remains hydroxyurea used to treat Sickle Cell Disease and, less successfully, β-thalassemia (page 2, left column, last paragraph). Yu et al (Current Opinion in Hematology, (2020), 27(3), 129-140), also cited for evidentiary purposes only, teaches that both clinical and laboratory evidence indicates that increasing the levels of fetal hemoglobin (HbF) alleviates the symptoms of Sickle Cell Disease, but fewer than half of all Sickle Cell Disease patients are responsive to hydroxyurea treatment, and the responses after 2 years of treatment were modest and diminished over time (page 3, third and fourth paragraphs). Autonomous control plays a major role in the silencing of the human embryonic (ε) and fetal (γ) globin genes in definitive erythroid cells; and a better understanding of the mechanism of autonomous silencing of the two γ-globin genes in adult erythroid cells may well lead to insights into novel strategies for re-activation of fetal globin transcription for the benefit of Sickle Cell Disease patients (page 5, first paragraph).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art” In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970).
Accordingly, the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statutory requirements. Furthermore, the mechanism of action of anticancer agents is often unknown or highly unpredictable, and the administration of such agents is frequently accompanied by undesirable side effects.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides data for increasing human fetal (γ) and embryonic (ε) hemoglobin expression in human CD34+ erythroid cells with PTC-596 AND MI-3454 in vitro in Example 3 on page 47, but it is not sufficient to provide support for the full scope of compounds that inhibit the activity of BMI1 or the MLL complex, or ß-globinopathy diseases or disorders encompassed by the claims.
The specification provides no particular direction or guidance for determining the particular administration regimens (e.g. timing, administration routes, etc) necessary to treat ß-globinopathy in a subject with any compound that inhibits the activity of BMI1 or the MLL complex encompassed by the claims, particularly in humans. At best, an "effective amount" is exemplified as a dosage sufficient to provide treatment for ß-globinopathy.
While experimentation is presented for increasing γ and ε hemoglobin expression with PTC-596 and MI-3454 in human CD34+ erythroid cells in vitro, there is not sufficient experimentation or mechanism or action data presented or discussed in the specification regarding the use of any compound that inhibits the activity of BMI1 or Mixed Lineage Leukemia complex to treat ß-globinopathy in a subject, particularly in humans.
Moreover, while Example 1 on page 46 and Example 2 on pages 46-47 respectively do provide limited data regarding the BMI1 and the MEN1/KMT2A (MLL1) interaction pathways, and hemoglobin expression in MEL cells, the variability observed among the limited disclosed inhibitor species suggests the claimed therapeutic activity may depend on compound specific properties beyond merely the inhibition of BMI1 or MEN1/KMT2A interactions, and thus does not support the full breadth of the claimed functional genus.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed in supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that any compound that inhibits the activity of BMI1 or Mixed Lineage Leukemia complex could be predictably used as treatment for all conditions or disorders associated with ß-globinopathy.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" (42 USPQ 2d 1001, Fed. Circuit 1997). A review of the state of the art fails to reveal the mechanism of action or experimental data regarding the use of any compound that inhibits the activity of BMI1 or Mixed Lineage Leukemia complex in the specification to treat any ß-globinopathy related disease or disorder. Determining if any particular claimed compound would treat a conditions or disorders associated with ß-globinopathy would require synthesis of the compounds, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. As noted in supra, even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of instant claims 1-2, 5, 10 and 20-35 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Conclusion
Claims 1-2, 5, 10 and 20-35 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER L JOHNSON whose telephone number is (571)272-1672. The examiner can normally be reached Monday - Friday 08:00AM - 5:00PM EST with Flex on Fridays.
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/C.L.J./Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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