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 Status
Claims 1, 7-8, 10, 24, 26-27, 30-31, 34, and 44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 11, 14-15, 17, 20, 22-23 and new claims 45-46 are under consideration in this office action.
Withdrawn Objections/Rejections
The objection to the specification for containing an embedded hyperlink is withdrawn; an amended specification was filed July 21, 2026.
The rejection of claims 11-12, 15, 17, and 20-23 under 35 U.S.C. 112(b) for being indefinite for use of the relative term “high” to describe ratio is withdrawn in view of applicant’s amendment of claim 11 to include the limitation wherein the ratio is “greater than or equal to 1.0”.
The rejection of claims 11-12, 14-15, 17, and 21 under 35 U.S.C. 112(a) for failing to meet the written description requirement is withdrawn in view of applicant’s amendment to limit “cancer therapy” in claim 11 to “Disulfide bond Disruption Agent (DDA)”. Regarding the examiner’s assertion that the genus DDA is not sufficiently described, applicant’s arguments filed July 21, 2026 supporting DDAs as a structurally defined class with a common structure-function relationship (pg 11-12) are persuasive.
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 11, 14-15, 17, 20, 22-23 and new claims 45-46 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 a method of determining tumor sensitivity to DDAs comprising calculating the ratio of oligomeric to monomeric ERp44 and PDIA1, does not reasonably provide enablement for a method for treating a tumor comprising administering a DDA in a patient with a tumor where the patient has a oligomeric to monomeric forms of Erp44, PDIA1, or AGR2 ratio greater than or equal to 1.0. 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.
Case law holds that applicant’s specification must be “commensurately enabling [regarding the scope of the claims].” See Ex Parte Kung, 17 USPQ2d 1545, 1547 (Bd. Pat. Appl. Inter. 1989). Otherwise, undue experimentation would be involved in determining how to practice and use applicant’s invention. Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described in In re Colianni, 195 USPQ 150 (CCPA 1977) and have been adopted by the Board of Patent Appeals and Interferences in Ex Parte Forman, 230 USPQ 546 (BPAI 1986). Among these factors are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the breath of the claims,
5. the amount of direction or guidance present, and
6. the presence or absence of working examples.
The following is an analysis of these factors in relationship to this application.
Nature of the invention/Breadth of claims
The nature of the invention is a method of treating a tumor in a patient who is determined to have a high ratio of oligomeric/monomeric forms of Erp44, PDIA1, or AGR2 relative to healthy controls, where the relative level of skill of those in the art is deemed to be high. With respect to claim breadth, the standard under 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. The method is for any patient having cancer, wherein the patient has a ratio of oligomeric/monomeric Erp44, PDIA1, or AGR2 of 1.0 or more, the method comprising administration of a DDA.
State of the Art/Predictability
Claims 11, 14, 20, 22-23, and new claim 45 are drawn to a method for treating a patient with a ratio of oligomeric to monomeric forms of ERP44, PDIA1, or AGR2 of 1.0 or greater, the method comprising administering DDA. In claims 15, 17, and new claim 46, the cancer is limited to glioblastoma, pancreatic cancer, or breast cancer. The claim requires a link between the presence of a ratio of oligomer to monomer of 1.0 or more and responsiveness to cancer treatment comprising DDA.
The prior art does not teach or suggest the claimed method because it fails to teach or suggest the link between high ratio of oligomeric to monomeric Erp44, PDIA1, or AGR2 in patients having cancer and a method of treating. Arumugam et al, published February 2, 2015 (see IDS from 3/27/2026) teaches that AGR2 is expressed in a wide variety of tumors, including breast, prostate, lung, and colorectal cancer (pg 941, column 1). Arumugan et al demonstrated that Inhibition of AGR2 with monoclonal blocking antibodies significantly reduced pancreatic ductal adenocarcinoma tumor weight and metastasis and prolonged survival in a xenograft mouse model (pg 942, column 1). Wang et al, published December 10, 2019 (see IDS from 3/27/2026) teach that DDAs kill cancer cells that overexpress EGFR or HER2 but that the mechanism is unknown (pg 2, column 1). Lee et al, published June 5, 2017 (PTO-892 from 4/21/2026) teach the PDI family members AGR2, PDIA1, and Erp44 (Table 1) and PDI contribute to tumorigenesis and metastasis (abstract). The art at the time the application was filed understood that DDAs were efficacious in the treatment to cancer and that alterations in AGR2, PDIA1, and Erp44 are related to cancer pathophysiology.
Guidance/working examples
Applicant’s disclosure demonstrates that tumors sensitive to PDI inhibitors are those in which the PDI proteins Erp44 and PDIA1 are fully engaged in disulfide bonds with client proteins; thus, the ratio of oligomeric to monomer Erp44 and PDIA1 is predictive of tumor sensitivity to Erp44 or PDIA1 inhibitors (Spec, pg 3). Treatment of mice with the claimed DDA is effective in reducing tumor growth and liver metastases in mice bearing HCI-001/LVM2 breast cells, a breast cancer cell line, compared to vehicle control (Spec, pg 67-68)).
The specification provides general guidance concerning the threshold of the high ratio of oligomer to monomer and the method for treating cancer with DDA (see, e.g., pp. 27-28 and pp. 42-43). “High ratio” can refer either to a oligomer/monomer ratio greater than the ratio for the same protein taken from a healthy subject sample (pg 22) or a ratio greater than or equal to 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1.0, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, 1.95, 2.0, 2.5, 3.0., 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 100, 200, 300, 400, 500, 1000, 10000, 100000, or 1000000 (pg 23).
The examples and disclosure are quite limited with respect to the claim scope because of the general degree of the demonstrated elevation of the oligomer to monomer ratio. The full scope of the claimed method encompasses treating a patient with an oligomer/monomer ratio greater than 1.0. The specification, however, does not provide data establishing the relationship between a particular oligomer/monomer ratio and treatment efficacy, including the significance of the claimed threshold of 1.0 or more. Although the specification may enable determination of the oligomer/monomer ratio, it does not enable, without undue experimentation, the full claimed scope of treating disease based on the claimed ratio.
Specification teaches that “the ratio of oligomeric to monomeric ERp44 and PDIA1 is predictive of tumor sensitivity to ERp44 or PDIA1 inhibitors, and this this can be examined by non-reducing immunoblot of tumor biopsies” [0007],[0080]. The specification teaches a general concept, where elevated oligomer/monomer ratio is predictive of responsiveness to DDA therapy, but it does not appear to establish what numerical ratio corresponds to efficacy. There are no experimental data demonstrating the claimed numerical relationship. Why is 1.0 selected as the threshold? Even if the general correlation is supported by the specification, this finding does not necessarily enable the specifically claimed cutoff. The specification does not provide sufficient evidence or technical guidance to demonstrate that a ratio greater than 1.0. Is predictive of treatment efficacy. Thus, the skilled artisan would have to undertake undue experimentation to determine whether the claimed numerical threshold could be used to identify patients who would benefit from the treatment.
MPEP 2164.03 teaches that “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, 839, 166 USPQ 18, 24 (CCPA 1970). The amount of guidance or direction refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as how to make and use the invention in order to be enabling.”
The instant specification is not enabling for the method of the claims because one cannot follow the guidance presented therein, or within the art at the time of filing, and predictably practice the claimed method without engaging in extensive and undue experimentation. Given that the nature of the invention is treatment of a person having cancer, a person having ordinary skill in the art would have to perform multiple further in vivo experiments, in animals and/or human subjects, in order to demonstrate whether the invention could or could not be used. Given the above unpredictability, and in view of the complex nature of the invention, a lack of sufficient disclosure in the specification, and little is known in the art concerning the claimed invention, there would be an undue quantity of experimentation required for one of skill in the art to practice the claimed invention, that is commensurate in scope of the claims.
In view of the foregoing, the full scope of the instant 11, 14-15, 17, 20, 22-23 and new claims 45-46 are not enabled.
Response to Arguments
Applicant's arguments filed July 21, 2026 have been fully considered. With respect to enablement and treatment of any cancer with elevated oligomer/monomer ratio with DDA (pg 13-14), applicant’s arguments are persuasive. The prior rejection under 35 U.S.C. 112(a) is withdrawn; however, applicant’s amendment to limit the oligomer/monomer ratio threshold to 1.0 or greater has altered the claim scope and has necessitated a new ground of rejection for not being fully enabled. Although applicnat has demonstrated a general biological correlation between oligomerization and treatment efficacy with DDAs, especially given the role of DDAs in reducing oligomerization and their efficacy in treating cancer, the specification does not teach sufficiently the claimed numerical relationship to enable its use as the claimed predictor of therapeutic efficacy.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at (571)272-0911. 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.
Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
Prosecution Insights