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 .
DETAILED ACTION
Priority
2. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-3, 6-7, 25, 28-29, 33-40, 58, and 66 have an effective filing date of 12/23/2019.
Information Disclosure Statement
3. The information disclosure statements (IDS) submitted on 10/29/2025 and 12/31/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restriction
In the response filed on 7/11/2025, Applicant elected:
Group I, claims 1-3, 6-7, 25-26, 28-31, 33-40, 42-43, 58, and 66
Species
a distinct species of number of pepmixes used
two pepmixes
a distinct species of mer for pepmix
15mer
a distinct species of antigen overlap
11 aa overlap
a distinct species of subsequent time points
2 subsequent time points
a distinct species of treatment used
chemotherapy
a distinct species of antigen covered by pepmixes
2 antigens covered by pepmixes
Status of Claims
Claims 1-3, 6-7, 25, 28-29, 33-40, 58, and 66 are currently pending and presented for examination on the merits.
Claims 1-2, 25, 33-34, and 58 are amended.
Claims 4-5, 8-24, 26-27, 30-32, 41-57, and 59-65 are canceled.
Rejections Withdrawn
The rejection of claims 1-3, 6, 7, 33-40, 42, 43, and 66 filed under 35 U.S.C. 101 is withdrawn in view of Applicant’s amendments to the claim.
The rejections filed under 35 U.S.C. 112(b) are withdrawn in view of Applicant canceling the claims.
The rejections filed under 35 U.S.C. 103 are withdrawn in view of Applicant’s amendments to claims.
Rejections Maintained
The rejection of claims 25, 28, 29, and 58 filed under 35 U.S.C. 101 is maintained. In Applicant Arguments, dated 01/12/2026, Applicant asserts that “[i]ndependent claims 25 and 58 are amended herewith to recite methods of detecting changes in a TAA expression profile of a tumor over time after a specific cancer treatment (e.g., chemotherapy, immunotherapy, radiation therapy, resection surgery, solid tissue transplant, a stem cell transplant, an autologous or allogenic antigen specific T cell therapy, or a combination thereof).”
Independent claims 1, 2, 33, and 34 have been amended, such that the claim recites a method of cancer treatment that integrate the claimed judicial exception (the natural correlation between an immune response elicited by T cells and the diagnosis of a tumor) into a practical application. The claimed judicial exception is used in a method of determining whether cancer treatment is appropriate. Claims 25 and 58 have been amended to recite treatment steps; however the claims still lack steps that integrate the claimed judicial exception (the natural correlation between an immune response elicited and the expression of a tumor antigen) into a practical application, because unlike independent claims 1, 2, 33, and 34, the claimed judicial exception is not used in a method of determining whether cancer treatment is appropriate. For amended claims 25 and 58, the claims identify immune response changes both before and after treatment, but these steps do not amount to significantly more than the claimed judicial exception.
New Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 6-7, 25, 28-29, 33-40, 58, and 66 are rejected under 35 U.S.C. 103 as being unpatentable over Leen et al (US 20180250384 A1), and further in view of Slanetz et al (WO 2018005712 A1).
In regard to claims 1, 25, 33-34, and 58, Leen et al teaches method of identifying whether or not antigens from a particular pathogen are immunogenic, including the order of their immunogenicity [Abstract]. Leen et al further teaches using peripheral blood mononuclear cells (PBMCs) obtained from cancer patients and undergoes a culture process [0011]. Leen et al further teaches exposing the PBMCs to two or more antigens and let T cells that recognize that antigen multiply in quantity [0011]. Leen et al further teaches the antigens are from the cancer [0011]. Leen et al further teaches antigens may be multiple antigens from the same entity, such as from the same pathogen or from the same cancer type (including tumor antigens) [0074]. Leen et al further teaches the antigen is antigenic peptides are provided to the PBMCs in a library of peptide mixtures, or pepmixes [0106]. Leen et al further teaches measuring the T cells response to antigens [Fig. 22]. Leen et al further teaches categorizing subjects in to responders and non-responders based on if the T cell bioactivity exceed a determined threshold [0013]. Leen et al further teaches methods of treating cancer [0019]. Leen et al further teaches a method of treating cancer [0019]. Leen et al further teaches immunotherapy [0009].
Leen et al does not specifically teach treating with chemotherapy and where in the tumor specific antigen (TSA) is neoantigen. However, this deficiency is made up in the teachings of Slanetz et al.
Slanetz et al teaches utilizing PBMCs to select tumor activated T cells [0092]. Slanetz et al further teaches the use of chemotherapy to treat tumors [0178].
One of ordinary skill, before the effective filing date, would have been motivated to use Leen’s methods of identifying and treating cancer based on whether or not antigens are immunogenic comprising obtaining a blood sample from a subject and culturing the PBMCs with tumor associated antigens stimulating the expansion of T cells, contact the T cells that have expanded with pepmixes, measuring whether there is a T cell response, and diagnosing if the response exceeds a determined threshold, and then treating the cancer comprising administering immunotherapy, with Slanetz’s method of treating cancer comprising chemotherapy and using neoantigens. It would have been prima facie obvious to use Leen and Slanetz’s teachings for a method of diagnosing the presence of a tumor in a subject and treating comprising: culturing PBMCs from the subject with pepmixes, wherein the culturing results in stimulating the expansion of T cells contained within the PBMCs obtained from the subject, measuring the response, diagnosing the subject if a T cell response is elicited, and treating the cancer with immunotherapy if the contact resulted in an immune response, because both Leen and Slanetz teach the expansion of PBMCs using pepmixes to known antigens and neoantigens, and both teach treating cancer. Furthermore, Slanetz teaches treating cancer comprising administering chemotherapy.
In regards to claim 2, Leen et al further teaches the use of dendritic cells in the methods [0106].
In regards to claims 3 and 37, Leen et al further teaches the use of multiple pepmixes [0314]. Leen et al further teaches that the peptides overlap [0113].
In regards to claim 6, Leen et al further teaches the peptides are 7-34 or more amino acids in length [0113].
In regards to claim 7, Leen et al further taches the overlapping of amino acids of 11 amino acids in length [0113].
In regards to claims 28-29, Leen et al further teaches subsequent challenges to T cells [0075].
In regards to claim 35, Leen et al further teaches PBMCs are obtained from cancer patients [0011].
In regards to claim 36, Leen et al further teaches culturing for 6-14 days [0121].
In regards to claim 38, Leen et al further teaches identifying multiple antigens [0006]. Leen et al further teaches at least two antigens from a cancer are identified [0008]. Leen et al further teaches the use of a variety of pepmixes [0106].
In regards to claim 39, Leen et al further teaches the peptides are 15 amino acids in length [0113].
In regards to claim 40, Leen et al further teaches the pepmixes overlapping by 11 amino acids [0113].
In regards to claim 66, Slanetz et al further teaches neoantigens used for T cell expansion [0234].
Applicant’s Arguments:
Examiner fails to provide any evidence or rationale for the a priori assertion that it "would be obvious" to apply Leen's method to an entirely different purpose or conclusion than taught by Leen.
Implied in this method is the understanding that before Leen's methods are performed, the immunogenicity of an antigen is unknown. A person performing Leen's method and finding that an antigen does not stimulate an immune response in immune cells isolated from an individual would conclude that the antigen is a "poor immunogen". Whether or not an antigen is or is not immunogenic is unrelated and independent of any conclusion about whether or not the individual "has a tumor". In fact, the present disclosure is based in part on the surprising discovery that antigens that have "low immunogenicity" (e.g., tumor associated antigens (TAAs)) can still be used to detect reactive T-cells in patients with tumors. Further, the level of reactivity by these T-cells surprisingly correlates with whether the patients have "active" or "inactive" tumors.
Leen does not provide any teaching or suggestion to apply the results of its methods (e.g., whether or not an antigen is or is not immunogenic) to a concrete treatment step since it was not known at the time of Leen that patients could have such disparate immune responses to the same antigen depending on the state of their tumor.
Examiner’s Response:
Applicant’s states, “A person performing Leen's method and finding that an antigen does not stimulate an immune response in immune cells isolated from an individual would conclude that the antigen is a "poor immunogen".”
Leen et al teaches measuring the biological response and comparing against a threshold value, the higher the value the higher the level of immunogenicity, along with the number of responders vs. non-responders [0014]. Leen et al does not teach away from an antigen for being “poor immunogen”, but rather does not filter out the T cells that have not undergone expansion. Furthermore, the immunogenicity of the T cells has been shown to be influenced by the tumor stroma. Spiotto et al teach the tumor stroma affects the level of antigen expression of cancer cells [Summary]. Spiotto et al further teaches nonimmunogenic tumors contain antigenic cancer cells that are potential targets for T cells [Left column, 4th Paragraph, pg. 745].
One of ordinary skill would recognize that the immunogenicity of PBMCs obtained from a subject is variable, and that nonimmunogenic tumors contain antigenic cancer cells that can be utilized for treatments.
Applicant states, “the present disclosure is based in part on the surprising discovery that antigens that have "low immunogenicity" (e.g., tumor associated antigens (TAAs)) can still be used to detect reactive T-cells in patients with tumors”
Applicant’s arguments of the surprising discovery that antigens that have “low immunogenicity” is not an element of the claims. Claim 1, part D, the treatment is administered “if the contacting in (b) does result in an immune response as measured in (c)”.
Conclusion
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 DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DENNIS J SULLIVAN/ Examiner, Art Unit 1642
/NELSON B MOSELEY II/ Primary Examiner, Art Unit 1642
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