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 .
Election/Restrictions
Applicant’s election without traverse of Group (I) in the reply filed on 10/27/2025 is acknowledged and maintained.
Priority
This application is a Continuation of U.S. application Ser. No. 16/279,289, filed Feb. 19, 2019, now Patent No. 11,607,742, which is a Continuation of U.S. application Ser. No. 15/468,815, filed Mar. 24, 2017, now Patent No. 10,213,448, which claims priority to U.S. Provisional Patent Application Ser. No. 62/313,417, filed Mar. 25, 2016. However, it is noted U.S. application Ser. No. 16/279,289, filed Feb. 19, 2019, now Patent No. 11,607,742, should be a Divisional of U.S. application Ser. No. 15/468,815, filed Mar. 24, 2017, now Patent No. 10,213,448
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on April 20, 2026. Claims 1, 4-8, and 10 are pending. Claims 2-3, and 11-20 are canceled. Claims 1, 4-8 and 10 are examined in accordance to the elected species.
Action Summary
The objection to claim 1, 4-8, and 10 are withdrawn in light of the claim amendment.
Claims 1, 4-8, and 10 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in light of the claim amendment.
Claims 1, 4-8, and 10 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement, are withdrawn in light of the claim amendment.
Claims 1, 4-8, and 10 rejected on the basis that it contains an improper Markush grouping of alternatives, are withdrawn in light of the claim amendment.
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, 4-8, and 10 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Present claim 1 is directed to a method of treating ovarian cancer in a subject comprising administering monoethanolamine (Etn) and a pharmaceutically acceptable carrier. Thus, the claims encompass treatment of ovarian cancer generally, including various stages, grades, subtypes, and disease states of ovarian cancer, including advanced ovarian cancer.
The specification provides experimental data relating to monoethanolamine. For example, the specification discloses pharmacokinetic studies, oral bioavailability studies, and formulation studies involving monoethanolamine. (See paragraphs [0013]- [0017].) Additionally, the specification discloses anti-proliferative effects against OVCAR-3 ovarian cancer cells and colony formation in vitro assays utilizing OVCAR-3 cell. (See paragraph 0018]- [0019].) The specification further teaches in vivo xenograft studies involving prostate. Colon, and breast cancer models. (See paragraphs [0021].)
However, the specification does not disclose any in vivo ovarian cancer efficacy model, ovarian cancer xenograft study, ovarian patient-derived xenograft (PDX) model, ovarian cancer animal study, or clinical ovarian cancer treatment data demonstrating that monoethanolamine effective treats ovarian cancer in a subject.
There are several guidelines when determining if the specification of an application allows the skilled artisan to practice the invention without undue experimentation. The factors to be considered in determining what constitutes undue experimentation were affirmed by the court in re Wands (8 USPQ2d 1400 (CAFC 1986)).
(1) Breadth of the Claims
The claims broadly encompass treatment of ovarian cancer in a subject and are not limited to any particular ovarian cancer subtype, disease stage, disease severity, patient population, treatment history, dosage regimen, or treatment setting. Thus, the claims encompass early-state ovarian cancer, advanced stage ovarian cancer, recurrent ovarian cancer, metastatic ovarian cancer, platinum-resistant ovarian cancer, and multiple ovarian cancer subtypes.
(2) Nature of the Invention
The claimed invention is directed to therapeutic treatment of ovarian cancer in a subject. Therapeutic treatment of cancer constitutes a complex and unpredictable field involving biological variables including tumor heterogeneity, tumor microenvironment, disease progression, and patient-specific responses.
(3) State of the Art
The state of the art did not recognize monoethanolamine as an established therapy for ovarian cancer. Therefore, a person of ordinary skill in the art could not rely upon a developed body of knowledge demonstration therapeutic efficacy of monoethanolamine for treating ovarian cancer. Instead, such a person would necessarily rely upon the teachings of the present specification to practice the full scope of the claimed invention.
Furthermore, Agadjanian et al (Sci Rep 15, 34969 (2025)) teaches ovarian cancer is a heterogeneous disease characterized by late-stage diagnosis and poor survival rates. Research efforts are hindered by the complexity of the tumor microenvironment and the lack of suitable preclinical models. While immortal human cell lines and patient-derived xenograft (PDX) models have contributed significantly to understanding tumor biology, they are limited by their immunodeficient nature, which precludes the study of immune-mediated mechanisms. Genetically modified mouse models of ovarian cancer address this limitation but the long and unpredictable tumor latency is impractical for testing therapies. (See second paragraph of page 1.) Moreover, Agadjianian teaches with the plethora of syngeneic ovarian cancer cell lines to choose from, is there a need for additional cell lines? The effectiveness of currently available therapies for treating ovarian carcinomas remains limited, largely due to the heterogeneous nature of these tumors. Ovarian carcinomas encompass a variety of distinct mutant genotypes, each of which exerts diverse and often poorly understood influences on tumor phenotypes. These influences extend to critical factors such as the tumor’s microenvironment and its response to treatment. This complexity poses significant challenges, particularly in developing and evaluating new immunotherapies. Our limited understanding of the mechanisms by which cancer genotypes shape both immunophenotypes and therapeutic responses further complicates efforts to improve outcomes in this disease. (See fifth paragraph of page 2.)
In sum, Agadjanian teaches that ovarian cancer is a heterogenous disease characterized by substantial biological diversity, molecular complexity, and variable therapeutic responses. Agadjanian also teaches that the current available preclinical models possess limitations in predicting clinical outcomes. Such teachings demonstrate therapeutic efficacy across ovarian cancer populations cannot readily be extrapolated from the limited experimental data.
Chua et al (“Advanced Ovarian Cancer: What You Need to Know” December, 29, 2025) teaches ovarian cancer is not one single disease — it’s a type of gynecologic cancer (cancer of the female reproductive system). Cancers that fall under this umbrella include tumors that grow in the ovaries, fallopian tubes, and peritoneum (tissue that lines the inside of your abdomen). Some ovarian cancers are caught early, when the tumor is still small. Others are more advanced, meaning the tumors have grown larger or spread to other organs. Advanced ovarian cancer is usually harder to treat and has a worse outlook. (See first and second paragraphs.)
In sum, Chua teaches that ovarian cancer encompasses diverse diseases presentations and that advanced ovarian cancer remains difficult to treat and is associated with poor clinical outcomes. Since the present claims are not limited to any particular stage of ovarian cancer, the claims encompass such difficult-to-treat disease states.
(4) Predictability or Unpredictability of the Art
The art is highly unpredictable. Tudrej et al. (Diagnostics 2019, 9, 120; pages 1-26) teaches ovarian cancer heterogeneity must be taken into account when selecting xenograft models and further note that, while OVCAR4 is indicated as a high-grade serous ovarian cancer (HGSOV) model, OVCAR3 is considered an HGSOV model only ‘with some doubt,” evidencing uncertainty regarding representativeness of OVCAR3 for clinically relevant ovarian cancer subtypes. (See first two paragraphs under “Xenografts Using Established Cell Lines” Section of page 7.) Tudrej et al. also teaches animal models are indispensable for both basic and preclinical research. They allow for the better understanding of the etiology and pathogenesis of diseases, identify potential therapeutic targets, and test novel therapeutic approaches. Unfortunately, there is no ideal in vivo system that would allow the modelling of all stages of development and progression of human ovarian cancer and to test drug responses. (See first paragraph under “Conclusion Sections” of page 18.) Tudrej et al. further teaches that ovarian cancer is a heterogeneous disease and that available cancer model systems possess significant limitations. (See Abstract.)
Accordingly, the evidence of record demonstrates that ovarian cancer is highly heterogenous and unpredictable disease area in which available preclinical models have significant limitations. Because the specification relies primarily on results obtained from a single OVCAR3 cell-line model, and does not provide corresponding ovarian cancer animal-model efficacy data, clinical data, or evidence demonstrating efficacy across the various ovarian cancer subtypes encompassed by the claims, a person of ordinary skill in the art would have been required to engage in undue experimentation to determine whether Etn is therapeutically effective throughout the full scope of the claimed invention.
Mak et al (Am J Transl Res. 2014 Jan 15;6(2):114–118) teaches the average rate of successful translation from animal models to clinical cancer trials is less than 8%. Animal models are limited in their ability to mimic the extremely complex process of human carcinogenesis, physiology and progression. Therefore, the safety and efficacy identified in animal studies is generally not translated to human trials. (See Abstract.)
Accordingly, anti-proliferative activity observed in a single ovarian cancer cell line cannot reasonably establish that monoethanolamine will effectively treat ovarian cancer throughout the full scope of the presently claimed invention.
(5) Amount of Direction or Guidance Presented
The specification provides limited guidance with respect to the treatment of ovarian cancer. The only ovarian cancer-specific data identified in the specification are in vitro OVCAR-3 cell viability and colony formation studies. (See paragraphs [0018] – [0019].) The specification does not provide guidance demonstrating therapeutic treatment of ovarian cancer in an animal model for human subject.
Furthermore, although the specification references oral administration and oral formulations containing Etn (see paragraphs [0140]-0143] and [0163]-0167]), the specification does not provide a specific pharmaceutical composition corresponding to the claimed composition comprising Etn and a pharmaceutically effective carrier. The disclosure lacks formulation details identifying the carrier system, composition, proportions, or preparation of the administered formulations. Consequently, the specification provides limited guidance regarding the full scope of the claimed pharmaceutical compositions for the ovarian cancer treatment.
(6) Presence or Absence of Working Examples
Although the specification contains working examples relating to OVCAR-3 ovarian cancer cells and in vivo studies involving other tumor types, the specification lacks any working examples demonstrating treatment of ovarian cancer in vivo. Notably, paragraph [0021] demonstrates the inventors concluded in vivo efficacy studies in prostate, colon, breast cancer models. However, no corresponding ovarian cancer in vivo efficacy study is disclosed despite the present claims being directed to the treatment of ovarian cancer.
(7) Quantity of Experimentation Necessary
In view of the absence of ovarian cancer in vivo efficacy data, the heterogeneity of ovarian cancer described by Agadjanian, the clinical complexity of ovarian cancer described by Chua, the unpredictability of translating preclinical findings to therapeutic efficacy discussed by Mak, and the significant limitations of available ovarian cancer model systems and the absence of an ideal model representation all stages of ovarian cancer explained by Tudregj, a person of ordinary skill in the art would be required to engage in substantial experimentation to determine whether monoethanolamine effectively treats ovarian cancer in a subject across the full scope of the claims.
Such experimentation would include determining whether the observed in vitro OVCAR-3 activity translate to in vivo efficacy, identifying responsive ovarian cancer subtypes, establishing effective therapeutic regimens, determining efficacy in advanced and recurrent ovarian cancer, and evaluating therapeutic effectiveness in subjects.
Accordingly, the specification does not provide an enabling disclosure commensurate in scope with the presently claimed invention and would require undue experimentation to practice the full scope of the claimed methods.
Acknowledgement is made of the receipt and entry of Applicant’s arguments/remarks filed on April 20, 2026.
Applicant argues that Example 3 demonstrates the ability of monoethanolamine (Etn) to inhibit proliferation of representative cancer cell lines from different tissue types, including ovarian cancer cell line OVCAR-3, and that Etn exhibited antiproliferative activity against OVCAR-3 cells in an MTT assay.
In response, Applicant’s argument is not persuasive. While Example 3 demonstrates that Etn exhibited antiproliferative activity against OVCAR-3 cell in vitro, the pending claims are directed to a method of treating ovarian cancer in a subject. The in vitro activity of a single ovarian cancer cell line does not establish Etn effectively treats ovarian cancer in vivo across the full scope of the claimed invention. The specification contains no ovarian cancer animal model, no ovarian cancer xenograft study, no ovarian cancer orthotopic model, no ovarian cancer metastatic model, and no ovarian cancer survival data. Therefore, the specification fails to demonstrate that the observed in vitro activity translates into therapeutic efficacy for ovarian caner in a living subject.
Applicant argues that Example 3 demonstrates broad application of Etn inhibiting a variety of cancer cell types.
In response, Applicant’s argument is not persuasive. The fact that Etn may exhibit antiproliferative activity against several cancer cell lines does not establish enablement of the presently claimed method of treating ovarian cancer. Ovarian cancer is recognized in the art as a heterogenous disease comprising multiple histological and molecular subtypes with distinct biological behaviors and therapeutic responses. Agadjanian et al. teaches that ovarian cancer heterogeneity must be considered when evaluating ovarian cancer models and therapeutic approaches. Consequently, activity against a single ovarian cancer cell line does not establish efficacy throughout the full scope of ovarian cancer encompassed by the claims.
Applicant additionally argues that Example 4 demonstrates in vivo efficacy of Etn in prostate, colon, and breast cancer xenograft models and that these data, when viewed together with the in vitro ovarian cancer data, would have provided a skilled artisan with a reasonable expectation that Etn would successfully treat ovarian cancer.
In response, Applicant’s argument is not persuasive. Example 4 is limited to prostate, colon, and breast cancer xenograft models. None of the in vivo studies disclosed in the specification involves ovarian cancer. Therapeutic efficacy observed in one cancer type does not necessarily predict efficacy in different cancer type, particularly where the claimed cancer is recognized as biologically heterogenous and clinically complex. Chua et al. teaches that ovarian cancer remains clinically challenging disease and that advanced ovarian cancer is particularly difficult to treat. The pending claims are not limited to any specific stage, grade, subtype, or severity of the ovarian cancer and therefore encompass advanced ovarian cancer as well as numerous ovarian cancer subtypes. The specification provides no in vivo data addressing any such embodiments.
Applicant argues that the in vitro data and in vivo data presented in the specification establish a correlation sufficient for a skilled artisan to expect successful treatment of ovarian cancer.
In response, Applicant’s argument is not persuasive. The issue is not whether some correlation exists between the disclosed in vitro and in vivo studies. Rather, the issue is whether the specification enables the full scope of the claimed invention without undue experimentation. Mak teaches that translation of preclinical findings into successful therapeutic outcomes is highly uncertain and that promising preclinical results frequently fail to predict clinical efficacy. Tudrej similarly teaches that ovarian cancer model systems possess significant limitations, that ovarian cancer is highly heterogenous, and that no ideal model exists that captures all stages and progression patterns of human ovarian cancer. Tudrej further notes uncertainty regarding the representativeness of OVCAR-3 as a clinically relevant model of high-grade serous ovarian cancer. Accordingly, a skilled artisan would not reasonably predict successful treatment of the full scope of ovarian cancers based solely upon the limited OVCAR-3 in vitro data and unrelated in vivo studies conducted in prostate, colon, and breast cancer models.
Applicant’s argument also fails to address the absence of ovarian cancer in vivo efficacy data in the specification. The disclosure provides only a single ovarian cancer cell line experiment and therefore does not provide sufficient guidance demonstrating how to successfully treat ovarian cancer in a subject across the full scope of the claims.
Accordingly, in view of (1) the absence of ovarian cancer in vivo efficacy data, (2) the heterogeneity of ovarian cancer as described by Agadjanian et al. and Tudrej et al., (3) the clinical complexity and treatment difficulty of ovarian cancer described by Chua et al., and (4) the unpredictability associated with translating preclinical findings into therapeutic efficacy as described by Mak et al., the specification would require undue experimentation for a skilled artisan to practice the full scope of the claimed method of treating ovarian cancer.
Conclusion
Claims 1, 4-8, and 10 are not allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEAN P CORNET whose telephone number is (571)270-7669. The examiner can normally be reached Monday-Thursday from 7.00am-5.30pm.
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, Amy L Clark can be reached at 571-272-1310. 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.
/JEAN P CORNET/Primary Examiner, Art Unit 1628
Prosecution Insights