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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/19/2025 was filed after the mailing date of the non-final rejection on 7/29/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
Response to Arguments
Applicant’s arguments, see Applicant Reply page 26, para. 2, filed 12/19/2025, with respect to objections to the specification have been fully considered and are persuasive. Amendments to the specification address the trademark issues raised previously. The objections to the specification have been withdrawn.
Claim Status
Claims 1, 31, 32, 34, 38, 39, 42, 52, 53, and 61-68 are pending. Claims 1, 31, 32, 34, 38, 39, 42, 52, 53, and 61-68 from the 12/19/2025 submission are under examination. Claims 3, 7-11, 19, 25, 27, 29, and 60 are canceled.
Claim Objections
Response to Arguments
Applicant’s arguments, see Applicant Reply page 26, para. 3, filed 12/19/2025, with respect to objections to the claims have been fully considered and are persuasive. Claim 1 has been amended to resolve the objection and claims 3 and 7-11 were canceled, rendering those objections moot. The objection to claim 1 has been withdrawn.
Claim Rejections - 35 USC § 101
Response to Arguments
Applicant’s arguments, see Applicant Reply page 26, para. 4, filed 12/19/2025, with respect to claim 60 have been fully considered and are persuasive. Claim 60 has been canceled, rendering this rejection moot.
New Rejection
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 61 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claim recites:
“A method of identifying an ALS patient that is likely to respond to treatment with a compound, which method comprises: a) isolating fibroblasts from the ALS patient, b) culturing the fibroblasts under conditions suitable to generate patient derived astrocytes, c) co-culturing the patient derived astrocytes with mouse motor neurons (MN) in the presence of the compound, and d) identifying the patient as being likely to respond to treatment with the compound, when MN cell degeneration or death is inhibited by the compound as compared to a non-treatment control; wherein the compound is a compound or salt of claim 1.”
Claim 61 is drawn to a process, so claim 61 passes Step One of the U.S.C. 101 analysis found in MPEP 2106(III).
Regarding Step 2A Prong One, claim 61 recites a mental process, which is an abstract idea. MEP 2106.04(a)(2)(III) recites: “The courts consider a mental process (thinking) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). As the Federal Circuit explained, "methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work’ that are open to all.’" 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972)). See also Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) ("‘[M]ental processes and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work’" (quoting Benson, 409 U.S. at 67, 175 USPQ at 675)); Parker v. Flook, 437 U.S. 584, 589, 198 USPQ 193, 197 (1978) (same).
Accordingly, the "mental processes" abstract idea grouping is defined as concepts performed in the human mind, and examples of mental processes include observations, evaluations, judgments, and opinions. A discussion of concepts performed in the human mind, as well as concepts that cannot practically be performed in the human mind and thus are not "mental processes", …”
Here, the step of “identifying” is a mental process that qualifies as abstract ideas under the guidelines described above.
Regarding Step 2A Prong Two of the analysis, this step requires a determination if the judicial exception is integrated into a practical application. This judicial exception is not integrated into a practical application because the steps of “isolating”, “culturing”, and “co-culturing” are steps utilized to gather information for the “identifying” step, and therefore occur before the “identifying” step, do not integrate the act of “identifying” into a practical application.
Next, Step 2B must be evaluated. The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps of isolating fibroblasts, culturing the fibroblasts, and co-culturing fibroblasts were routine and conventional in the art. (Kisiel, et al. Skin Tissue Engineering. Methods in Molecular Biology, vol 1993. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9473-1_6 (2019), pages 71-78). Therefore, they cannot amount to significantly more than the claimed judicial exception. Claim 61 is rejected.
Claim Rejections - 35 USC § 112
Response to Arguments
Applicant’s arguments, see Applicant Reply page 26, para. 4, filed 12/19/2025, with respect to the rejection of claims 1, 32, 34, 38, 39, 42, 52, 53, and 61 under U.S.C. 112a have been fully considered and are persuasive. Claims 3, 7-11, 19, 23, 25, 27, and 60 are canceled, rendering that rejection moot. The genus claimed by claims 1, 32, 34, 38, 39, 42, 52, 53, and 61 is now fully supported by the specification. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made below.
New Rejection
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 38, 39, and 42 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 a disease in a mammal which is treatable by activation of the EphA4 pathway, does not reasonably provide enablement for treating any disease merely associated with EphA4. 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.
MPEP 2164.01(a) states: “In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is ‘reasonable’ or is ‘undue.’”
These factors include, but are not limited to:
The breadth of the claims;
Claim 38 is not especially broad. However, the specification focuses on EphA4 binding events and activation.
The nature of the invention;
The invention is a method of treating a disease associated with EphA4 in a mammal.
The state of the prior art;
Miyazaki et al. (Miyazaki, et al. BMC clinical pathology 13.1: 19. (2013)) discloses that EphA4 can be diagnostic of gastric cancers: “EphA4 plays an important role in tumour progression and clinical outcomes, similar to EphA2, in patients with gastric cancer. EphA4 is an independent prognostic factor in stage II and III gastric cancer, stages that usually require adjuvant chemotherapy. The expression of EphA4 in primary tumours significantly correlated with that in metastatic lymph nodes. EphA4 may be a promising target for monoclonal antibody therapy in patients with gastric cancer.” (Miyazaki et al., page 8, col. 2, para. 2).
Similarly, van Doorn et al. (van Doorn, et al. Cancer research 64.16: 5578-5586. (2004)) discloses that EphA4 can be prognostic for Sezary syndrome: “Our studies indicate that malignant T cells of Sz patients display a gene expression pattern that separates them from benign T cells of patients with BE and healthy controls. Among the most highly and consistently expressed genes in T cells of Sz patients are the membrane-bound tyrosine kinase receptor EphA4 and Twist, a potentially oncogenic transcription factor. Additional studies are necessary to evaluate whether these tumor-associated proteins are involved in the development and progression of Sz and if they can be used as targets for therapeutic intervention.” (van Doorn et al., page 5585, col. 1, para. 4).
The level of one of ordinary skill;
One of ordinary skill in the art is high; typically a master’s level education or higher.
The level of predictability in the art;
The predictability for treatment of diseases using a complex signaling pathway is low.
The amount of direction provided by the inventor and the existence of working examples; and The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The specification enables the usage of the disclosed molecules for the binding and agonism of EphA4. The specification does not provide data for diseases that are not directly affected by agonism of the EphA4 pathway.
Regarding claim 38, Miyazaki and van Doorn show that disease states exist that are associated with EphA4, but the specification does not disclose the ability to treat these disease states. In fact, Miyazaki discusses the usage of antibody therapy against EphA4, not activation via agonism.
It would require undue experimentation for a person of ordinary skill in the art to test the molecules disclosed in the specification against all known diseases merely associated with EphA4. Consequently, claim 38 is rejected.
Regarding claim 39, claim 38 is rejected as described above. Miyazaki discloses a case wherein a cancer is associated with EphA4 but treatment of said cancer is not enabled by the present disclosure. Consequently, claim 39 is rejected.
Regarding claim 42, claim 39 is rejected as described above. Further defining neurodegenerative diseases does not change the above analysis for claim 39. Consequently, claim 42 is rejected.
Claim Rejections - 35 USC § 103
Response to Arguments
Applicant’s arguments, see Applicant Reply page 28, para. 4, filed 12/19/2025, with respect to claims 1, 32, 34, 38, 39, 42, 52, and 53 have been fully considered and are persuasive. Claims 3, 7, and 8 have been canceled, rendering the rejection of these claims moot. Applicant incorporated previously allowable claim 29 into claim 1, thereby rendering claim 1 and all dependent claims nonobvious. The rejection of claims 1, 32, 34, 38, 39, 42, 52, and 53 has been withdrawn.
Allowable Subject Matter
Claims 1, 31, 32, 34, 52, 53, and 62-68 are allowable because the peptides and methods disclosed are free of the prior art and fully supported and enabled by the specification.
Specifically, the core structure of 5-hydroxy-Trp (and modified derivatives thereof), biphenyl alanine (and modified derivatives thereof), and arginine was searched and only the molecules of the present Application were found.
Regarding claim 34, Applicant reports binding data for claimed molecules.
Regarding claims 52 and 53, Wu et al. (Wu, et al. Cell chemical biology 24.3: 293-305. (2017)) discloses targeting of EphA4 for motor neuron degeneration involving astrocytes: “Intriguingly, the agents act as EphA4 agonists in primary cortical neuron, suggesting that alternative mechanisms correlating EphA4 expression with disease progression may involve reverse signaling perhaps on ephrin-B2-expressing reactive astrocytes.” (Wu et al., page 292, col. 2, para. 2).
Conclusion
Claims 38, 39, 42, and 61 are rejected.
Claims 1, 31, 32, 34, 52, 53, and 62-68 are allowable
Any inquiry concerning this communication or earlier communications from the examiner should be directed to David Paul Bowles whose telephone number is (571)272-0919. The examiner can normally be reached Monday-Friday 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached on (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654