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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 16 December 2025 has been entered.
Status of the Claims
Applicant’s submission filed 16 December 2025 has been entered. Claims 53-72 are pending. Claims 61-64 have been amended, while claim 72 has been newly added. Therefore, prosecution on the merits continues for claims 61-64 and 72 as being drawn to the elected invention, while claims 53-60 and 65-71 are withdrawn for reading on non-elected inventions. All arguments have been fully considered with the status of each prior ground of rejection set forth below.
Status of Prior Rejections/Response to Arguments
RE: Objection to the Specification
The substitute Specification filed 16 December 2025 is acknowledged and entered into the application file. With that, Applicant’s amendments to the Specification obviate the objections of record.
Therefore, the objections are withdrawn.
RE: Information Disclosure Statement
The IDS filed 18 June 2025 and 22 October 2025 now comply with the provisions of 37 CFR 1.98(a)(4) because the appropriate size fee assertion is acknowledged.
Therefore, each IDS has been considered.
RE: Rejection of claims 61-64 under 35 USC 112(a)
Applicant has amended independent claim 61 to require the isolation and direct activation of T cells with 30 mcg to 4,000 mcg selenium and 150 mg to 5,000 mg fish oil.
With that, Applicant’s arguments in the Remarks filed 16 December 2025 have been fully considered but are not found persuasive.
Applicant has traversed the rejection, asserting in Pages 6-7 of the Remarks filed 16 December 2025 that the ordinary artisan would have recognized that the in vivo treatment of subjects with selenium and fish oil can be readily transferred to the ex vivo treatment of T cells, citing Applicant’s own work on the effects selenium and fish oil had on T cell activation surface markers within the subject, as well as the reference of Einloth et al. In response, the Examiner respectfully expresses the same concerns that Applicant asserted in Page 7 of the Remarks filed 18 June 2025, wherein Applicant submitted that “consumption as part of a diet is not equivalent to the direct application to a cell held in culture”. With that, the Examiner concludes that it is not readily apparent wherein Einloth et al teach that the activation of isolated immune cells using processes analogous to those occurring in nature followed by re-implantation is a therapeutic mode that would be known to a person of ordinary skill, and therefore does not provide sufficient evidence that the direct application of selenium and fish oil in vitro can provide a similar activation of T cells. In other words, the instant disclosure and Einloth et al fail to reasonably teach that the effects of the ingested selenium and fish oil will be the same or sufficiently similar to the direct application of selenium and fish oil to ex vivo cells, and that the ingested effects are not result of the metabolites of the selenium and fish oil after being processed within the subject.
The Examiner instead encourages Applicant to provide evidence in the form of a declaration detailing either post-filing or art-recognized work showing, even individually, that the in vitro incubation of specific T cell subsets with selenium and fish oil increases their activation, function, and/or proliferation, or that the in vivo effectiveness of these molecules can be predictably reciprocated in vitro. See MPEP § 716 for guidance.
Applicant has further traversed the rejection, asserting in Pages 7-8 of the Remarks filed 16 December 2025 that the burden for undue experimentation is lifted given that Applicant has narrowed the ranges in which the selenium and fish oil are effective. With that, Applicant cites a Federal Circuit case in which it was decided that “experiments involving repetition or commonly used techniques” are enabled. See Cephalon, Inc. v. Watson Pharm., Inc., 707 F.3d 1330, 1339-40 (Fed. Cir. 2013). In response, the Examiner respectfully submits that the burden is on Applicant to explain how the fact pattern in Cephalon, Inc v Watson Pharm., Inc is relevant to the pending claims. Applicant has not articulated how optimizing the “effective” dose of a known therapeutic drug in clinical trials is equivalent to the present situation: there is no basis that the claimed “dosages” are effective in vitro, and there is no presumption that any dosage used in vivo can be converted to in vitro usage to arrive at the claimed cells. Accordingly, broadly limiting the activating formulation to comprise 30 mcg to 4,000 mcg selenium and 150 mg to 5,000 mg fish oil in an amount effective to modulate expression of a protein associated with T cell activation does not sufficiently reduce the undue experimentation required of the ordinary artisan to effectively perform the method as claimed and arrive at the same results, as the recited ranges encompass a lower bound and an upper bound that has a differential of thousands of units, and are not associated with specific modulation of a protein associated with T cell activation.
Therefore, the rejection is maintained and modified to encompass the claims as written.
New/Maintained Grounds of Rejection
Claim Objections
Claims 61, 63-64, and 72 are objected to because of the following informalities:
Regarding claim 61: Given that Applicant has amended the other recitations of “immune cell”, the instant claim is objected to for reciting “immune cell” within Lines 1 and 8 instead of “T cell”.
Appropriate correction is required.
Regarding claim 63: The instant claim is objected to for reciting “comprising a step of clonally expanding the T cell to prior to contacting with the activating formulation…” instead of “comprising a step of clonally expanding the T cell [[to]] prior to contacting with the activating formulation…”, or the like.
Appropriate correction is required.
Regarding claim 64: The instant claim is objected to for reciting “comprising the step of genetically modifying the T cell or the activated T cell” instead of “comprising a step of genetically modifying the T cell or the activated T cell”.
Appropriate correction is required.
Regarding claim 72: The instant claim is objected to for reciting “wherein the a protein associated with T cell activation is Cluster of Differentiation (CD8)” instead of “wherein the [[a]] protein associated with T cell activation is Cluster of Differentiation (CD8)”.
Appropriate correction is required.
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 61-64 and 72 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 claims contain 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.
The instant claims as amended are directed to a method of activating T cells to enhance anti-tumor activity, comprising: isolating a T cell from an individual to be treated for cancer to generate an isolated T cell; activating the isolated T cell by contacting the isolated T cell with an activating formulation comprising 30 mcg to 4,000 mcg selenium and 150 mg to 5,000 mg fish oil in an amount effective to modulate expression of a protein associated with T cell activation in the isolated T cell to generate an activated T cell; and administering the activated T cell to the individual. Thus, the claims now require direct activation via 30 mcg to 4,000 selenium and 150 mg to 5,000 mg fish oil, which was not previously required. A review of the Specification shows that Applicant has not provided sufficient description of the invention to support they were in possession of an isolated T cell that has been activated and administered to an individual as recited in the instantly claimed method.
Possession of an invention may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998). Although working examples are not required, the claimed invention is required to be enabled so that any person skilled in the art can make and use the invention without undue experimentation. See MPEP § 2164.
The factors to be considered in determining whether a disclosure would require undue experimentation include:
A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 8 USPQ2d, 1400 (CAFC 1988) and MPEP § 2164.01.
Nature of the invention: Independent claim 61 is directed to a method of activating T cells to enhance anti-tumor activity, comprising: isolating a T cell from an individual to be treated for cancer to generate an isolated T cell; activating the isolated T cell by contacting the isolated T cell with an activating formulation comprising 30 mcg to 4,000 mcg selenium and 150 mg to 5,000 mg fish oil in an amount effective to modulate expression of a protein associated with T cell activation in the isolated T cell to generate an activated T cell; and administering the activated T cell to the individual. Thus, the claims now require the direct activation of the isolated T cell via 30 mcg to 4,000 mcg selenium and 150 mg to 5,000 fish oil, as indicated by the recitation of “contacting the isolated T cell with an activating formulation comprising 30 mcg to 4,000 mcg selenium and 150 mg to 5,000 mg fish oil in an amount effective to modulate expression of a protein associated with T cell activation in the isolated T cell to generate an activated T cell” (emphasis added).
The relative skill of those in the art: The relative skill of those in the art is high, with the majority of ordinary artisans possessing an advanced degree.
The breadth of the claims: With respect to claim breadth, the standard under 35 U.S.C. §112(a) entails the determination of what the claims recite and what the claims mean as a whole. In addition, when analyzing for enablement, the claims are analyzed with respect to the teachings of the Specification and are to be “given their broadest reasonable interpretation consistent with the Specification.” See MPEP § 2111 [R-5]; Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005); and In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the Examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).
As such, the broadest reasonable interpretation of the instantly claimed method as amended is that it provides for the direct activation of the isolated T cell via contacting the immune cell with an activating formulation comprising anything, so long as the activating formulation comprises 30 mcg to 4,000 mcg selenium and 150 mg to 5,000 mg fish oil in an amount effective to modulate expression – whether that be an increase or decrease – of any protein associated with T cell activation within the T cell. See Paragraph [0011] and Table 1 of the instant Specification. A skilled artisan would not know how to perform the recited method with a reasonable expectation of success based solely on what is disclosed in the Specification.
The amount of direction or guidance presented: The instant Specification recites generic and/or prophetic embodiments of the method with limited applicability or guidance to the invention as claimed. For example, the instant disclosure states that a conceptual aspect of the invention is a “method of treating cancer by treating blood or immune cells (such as NK cells) isolated from patient blood (for example, by leukapheresis) with active components of a nutritional supplement as described above (such as selenium and/or fish oil)”, and that “such ex vivo treatment can activate blood or immune cells and/or modulate expression of markers associated with improved antineoplastic immune function”. See Paragraph [0115] of instant Specification.
However, there is no disclosure wherein the ex vivo exposure of isolated T cells to selenium and fish oil directly activates the isolated T cells such that expression of a protein associated with immune cell activation is modulated.
Thus, these generic teachings fail to provide specific details necessary to successfully perform the claimed method, wherein the claims require the direct activation of the isolated T cells via contacting the isolated T cells with fish oil and selenium such that expression of a protein associated with T cell activation is modulated within the isolated T cells.
The presence or absence of working examples: There are no working examples that appear to encompass the claimed method of directly activating an isolated T cell by contacting the isolated T cell ex vivo with an activating formulation comprising selenium and fish oil in an amount effective to modulate expression of a protein associated with immune cell activation in the isolated immune cell. The instant Specification’s few working examples are directed to methods of treating cancer via the in vivo administration of selenium and fish oil directly to the subject in need thereof. See Paragraphs [0083]-[0089], [0098]-[0099], [0103]-[0109] of the instant Specification. Therefore, there is no disclosure in the Specification wherein the ex vivo exposure of selenium and fish oil to isolated T cells function to activate the isolated T cell such that expression of a protein associated with T cell activation is modulated.
The level of predictability in the art and quantity of experimentation necessary: The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention.
Before the effective filing date of the claimed invention, the closest prior art to the instantly claimed invention is Wang et al (PLoS One, 2013, of record). Wang et al disclose the administration of 20 mg fish oil and 0.69 mcg selenium to tumor-bearing mice, wherein the administration of fish oil and selenium synergistically reduces the suppressive effects of Tregs and MDSC cells on effector immune cells in mixed populations of immune cells (Abstract; Pages 4-5, 9; Figures 2E, F). Therefore, the prior art teaches the indirect activation of effector immune cells in vivo via the synergistic reduction of Tregs and MDSC cell populations. However, Applicant has previously argued within Page 6 of the Remarks filed 18 June 2025 – and the Examiner agrees – that consumption [of selenium and fish oil] as part of a diet is not equivalent to direct application to T cells in culture, and the ordinary artisan thereby cannot readily translate the in vivo results to the in vitro environment. The Examiner notes that the prior art does not disclose or otherwise suggest the direct activation of isolated T cells wherein the T cells are contacted with an activating formulation comprising 30 mcg to 4,000 mcg selenium and 150 mg to 5,000 mg fish oil in an amount effective to modulate expression of a protein associated with T cell activation in the T cell ex vivo.
In addition, Ecker et al (Cell Metab, 2018) disclose that the mechanisms by which T cells are activated and function in vitro and in vivo differ and may not be fully understood, especially in the context of a cancer subject and the tumor microenvironment. See Pages 191-192 of Ecker et al. Thus, an ordinary artisan would not predict that the nutritional supplement of Wang et al comprising selenium and fish oil results in the direct modulation of a protein associated with T cell activation, as claimed.
Therefore, a person having ordinary skill would have to perform undue experimentation in order to perform the method commensurate in scope with the breadth of the claims.
Consequently, the instant Specification is not enabling because one cannot follow the guidance presented therein, or within the art at the time of filing, and perform the claimed method without first making a substantial inventive contribution, as the instant disclosure has failed to provide working examples outlining the direct activation of the isolated T cells ex vivo via selenium and fish oil, and the prior art is unpredictable in regards to the translation of in vivo results to ex vivo applications, as taught by Ecker et al. Without explicit guidance in the disclosure as filed, a person having ordinary skill would have to perform undue experimentation in order to successfully activate the immune cells in a direct manner, as instantly claimed. Given that the nature of the invention is the activation of T cells isolated from an individual to be treated by cancer, and since the claims broadly encompass multiple methods, undue further experimentation would be required in order to demonstrate the method can be performed with a reasonable expectation of success.
Thus, in view of the Wands factors, as discussed above, Applicant fails to provide information sufficient to perform the claimed invention of a method of directly activating immune cells to enhance anti-tumor activity, as recited in instant claim 61. Instant claims 62-64 and 72 are included because they depend from a rejected claim.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner
should be directed to ALYSSA G WESTON whose telephone number is (571)272-0337. The examiner can normally be reached Monday-Thursday 8AM - 4PM (CT); Friday 8AM - 11AM (CT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA G WESTON/Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633