DETAILED ACTION
Disposition of Claims
Claims 1-10 were pending. Claims 2, 5, and 10 have been cancelled. Amendments to claims 1, 3-4, 6-9 are acknowledged and entered. Claims 1, 3-4, and 6-9 will be examined on their merits.
Examiner’s Note
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Unless otherwise noted, any reference to paragraphs (¶) of the instant application are referencing the PGPub of the instant application, US20230160875A1, Pub. 05/25/2023.
Response to Arguments
Applicant's arguments filed 02/23/2026 regarding the previous Office action dated 08/27/2025 have been fully considered. If they have been found to be persuasive, the objection/rejection has been withdrawn below. Likewise, if a rejection/objection has not been recited, said rejection/objection has been withdrawn. If the arguments have not been found to be persuasive, or if there are arguments presented over art that has been utilized in withdrawn rejections but utilized in new rejections, the arguments will be addressed fully with the objection/rejection below.
Optional Authorization to Initiate Electronic Communications
The Applicant’s representative may wish to consider supplying a written authorization in response to this Office action to correspond with the Examiner via electronic mail (e-mail). This authorization is optional on the part of the Applicant’s representative, but it should be noted that the Examiner may not initiate nor respond to communications via electronic mail unless and until Applicant’s representative authorizes such communications in writing within the official record of the patent application. A sample authorization is available at MPEP § 502.03, part II. If Applicant’s representative chooses to provide this authorization, please ensure to include a valid e-mail address along with said authorization.
Priority
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. This application repeats a substantial portion of prior Application No. 16/896,969, filed 04/20/2020, and adds disclosure not presented in the prior application. Because this application names the inventor or at least one joint inventor named in the prior application, it constitutes a continuation-in-part of the prior application. Multiple terms and limitations present in all pending claims (instant claims 1-10), including “B cell”, “B-cell marker(s)”, “peripheral blood mononuclear cells”, “SARS-COV-2”, “SARS-related Coronavirus-2”, the limitation of 7 days of incubation for the isolated B-cells, “activated B-cells”, “CD80”, “CD40”, “CD23”, “CD38”, “CD69”, “CD27”, “CD20”, or “CD86” as recited in claims 1-10 are not supported by the original parent disclosure as filed, and are therefore not afforded the earlier priority filing date. Therefore, the effective filing date of the present claims is 11/21/2022, or the filing date of this instant application.
Claim Objections
(Objection withdrawn.) The objection to Claim 4 is withdrawn in light of the amendments to the claim.
(Objection withdrawn.) The objection to Claim 9 is withdrawn in light of the amendments to the claim.
Claim Rejections - 35 USC § 112(b); Second Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claim 1 and dependent claims 2-5 thereof under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claims 4 and 9 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claim 6 and dependent claims 7-10 thereof under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claim 7 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendments to the claims.
(Rejection withdrawn.) The rejection of Claim 10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the cancellation of said claim.
(New rejection – necessitated by amendment.) Claims 3 and 7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 3 and 7 recite the limitation of "the plurality of B-cell markers comprise CD80, CD40, CD23, CD38, CD69, CD27, CD20, or CD86" in lines 1-2. The antecedent basis for this limitation remains unclear, as claims 3 and 7 depend upon claims 1 and 6, respectively, and it is unclear if per the method of claim 1 or 6 if all of these markers are to be monitored, or only a subset of these markers (e.g. one or more markers) can be analyzed, especially since the Markush group utilizes “or” instead of “and”, which suggests that the markers can be analyzed in the alternative and are not all required. If all markers should be analyzed, it is suggested the claims be amended to recite along the lines of “wherein the plurality of B-cell markers analyzed comprise CD80, CD40, CD23, CD38, CD69, CD27, CD20, and CD86.” However, if only one or more markers are analyzed, one suggestion is “wherein the plurality of B-cell markers monitored comprise one or more of CD80, CD40, CD23, CD38, CD69, CD27, CD20, and/or CD86.”
These are suggestions, as Applicant is free to amend the claims as they deem necessary to overcome this rejection.
(New rejection – necessitated by amendment.) Claim 6 and dependent claims 7-9 thereof are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 6 recites that there is a step of “monitoring a plurality of B-cell markers in the sample”. However, it is unclear if this monitoring of the sample is meant to monitor the sample of PBMC exposed to an antigen, the entire blood sample taken from the patient, or both.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant claim 6 is rejected on the grounds of being indefinite. Claim(s) 7-9 are also rejected since they depend from claim 6, but do not remedy these deficiencies of claim 6.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 1 is drawn to a method of stimulating immune cells ex vivo to a predetermined infectious disease in the absence of a vaccine, in a human patient who has not been previously exposed to the predetermined infectious disease, the method comprising the steps of:
drawing a blood sample from the human patient;
isolating all peripheral blood mononuclear cells (PBMC) in the blood sample;
stimulating a well seeded with some of the isolated peripheral blood mononuclear cells with 10uM CpG oligodeoxynucleotide;
incubating the seeded well at 37 degrees Celsius with five percent carbon dioxide overnight;
adding an antigen to the seeded well;
re-incubating the seeded well for six hours; and
conducting a flow cytometric analysis on a sample from the seeded well for a plurality of B-cell markers.
Further limitations on the method of claim 1 are wherein the plurality of B-cell markers comprise CD80, CD40, CD23, CD38, CD69, CD27, CD20, and/or CD86 (claim 3); and wherein the antigen is a peptide mixture comprising the immunodominant sequence domains of the severe acute respiratory syndrome (SARS) coronavirus type 2 (SARS-CoV-2) Spike (S) protein or a SARS-CoV-2-related isolate (claim 4).
Claim 6 is drawn to a method of activating a subset of B-cells taken from a human patient in vitro, the method comprising:
drawing a blood sample from the human patient;
isolating all peripheral blood mononuclear cells (PBMCs) from the blood sample,
exposing a sample of the isolated PBMC cells to an antigen,
monitoring a plurality of B-cell markers in the sample,
determining if a presence of markers for a B cell activation or a memory B cell marker occurs.
Further limitations on the method of claim 6 are wherein the plurality of B-cell markers comprise CD80, CD40, CD23, CD38, CD69, CD27, CD20, and/or CD86 (claim 7); wherein some of the activated B-cells are supplied to the human patient (claim 8); and wherein the antigen is a peptide mixture comprising the immunodominant sequence domains of the SARS-COV-2 Spike protein or a SARS-CoV-2-related isolate (claim 9).
Claim Rejections - 35 USC § 112(a); First Paragraph
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Rejection withdrawn.) The rejection of Claims 1-10 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is withdrawn in light of the amendments to the claims.
(New rejection – necessitated by amendment.) Claims 1, 3-4, and 6-9 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 stimulation of B cells from healthy, SARS CoV-2 seronegative donors, wherein said B cells are stimulated with ODN 2006 and overlapping SARS CoV-2 spike (S) protein peptides, does not reasonably provide enablement for stimulation of any B cells from any healthy, seronegative donor with any type of CpG oligodeoxynucleotide (ODN) and any antigen, nor does it reasonably provide enablement for re-introduction of the enabled SARS CoV-2 S protein stimulated B cells back into the patient from which they were derived. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to generic methods of stimulating immune cells in vitro or ex vivo through exposure to any antigen (wherein “antigen” reasonably includes any antigenic portion of any agent; claim 1 is specifically drawn to infectious agent antigens, which reasonably includes live, attenuated or inactivated pathogens), and identifying those activated B cells from said sample. Further dependent claims require the antigens to be peptides from immunodominant SARS CoV-2 S protein epitopes. Further steps in the claimed methods include re-introducing said stimulated B cells back into the patient. The method of claim 1 further provides for the stimulation of the isolated peripheral blood mononuclear cells (PBMCs) with any CpG oligodeoxynucleotide (ODN). The methods are therefore general methods of passive immunity using autologous ex vivo stimulated immune cells, namely white blood cells or B-cells separated from the blood sample.
“Pathogen” is interpreted as any entity introduced into a host that results in disease, such as bacteria, virus, fungi, protozoa, worms, or prions. “CpG oligodeoxynucleotides” (ODN) are short, synthetic single-stranded DNA molecules classified by structure and immune effects into three major types (A, B, and C) that activate TLR9, with a fourth, Class P, also recognized. They serve as potent immune adjuvants, particularly enhancing B cell and plasmacytoid dendritic cell (pDC) activity.
State of the prior art/Predictability of the art. As noted in the previous Office action, the breadth of the invention reads on the use of any type of antigen for the stimulation of the PBMCs. Stimulation of immune cells with a pathogen must be controlled in a precise manner with preferably an inactivated pathogen or the use of only nucleic acid, amino acid, peptide, or protein from said pathogen, as inoculation of a sample with live, active pathogen could have detrimental consequences on the sample, the immunostimulation process in vitro, and/or the host upon re-introduction of stimulated immune cells back into the host. Even limiting the pathogen to a live, attenuated pathogen is questionable as there will still be cytotoxic effects on the blood sample, as well as potential disease-causing effects in certain populations of patients (e.g. immunocompromised, elderly, neonates) upon introduction of the sample which comprises the live-attenuated pathogen. Further, the pathogen and antigen itself may have a role in the type of B cell antibody response stimulated. The induction of polyclonal B cell activation and the production of low-specificity antibodies are often associated with an early blunting of infections, but can also dilute pathogen-specific antibody responses. Some pathogens have evolved mechanisms to deliberately induce the production of low-specificity antibodies by direct interaction with B cells in order to subvert specific immune responses (Nothelfer K, et. al. Nat Rev Microbiol. 2015 Mar;13(3):173-84. Epub 2015 Feb 9; CITED ART OF RECORD.) Additionally, even with the use of inactivated or live, attenuated pathogens, this does not ensure the safety of the method, as certain inactivated pathogens can still result in disease (inactivated RSV caused an increased pathogenic effect in subjects upon subsequent viral challenge) and certain populations of subjects, such as infants or immunocompromised individuals, do not have sufficient immune responses to curtail the replication and pathogenic effect of live, attenuated vaccines (e.g. certain subjects should not receive the live, attenuated VZV, MMR, rotavirus, yellow fever, or smallpox vaccines.)
As noted supra, CpG ODNs (oligodeoxynucleotides) are short, synthetic single-stranded DNA molecules classified by structure and immune effects into three major types (A, B, and C) that activate TLR9, with a fourth, Class P, also recognized. They serve as potent immune adjuvants, particularly enhancing B cell and plasmacytoid dendritic cell (pDC) activity, albeit at different levels amongst each class. Class A (Type D) induce high levels of IFN-alpha and activate NK cells indirectly through pDCs, featuring a phosphorothioate (PS) backbone and a central palindrome. Class B (Type K) are strong stimulators of B cells and Th1 responses, with a fully phosphorothioate backbone, and they are the most common type used in clinical trials. Class C ODNs combine features of A and B, stimulating both high IFN-alpha production and strong B-cell activation. Class P ODNs combine the properties of A and B, designed to induce strong type-I IFN and inflammatory responses. Additionally, there are inhibitory ODNs which are used to reduce or inhibit immune-mediated inflammatory responses (e.g., antisense ODNs, DNA aptamers). Not all ODNs are potent stimulators of B cells, with class A ODNs primarily used to induce high levels of interferon-α (IFN-α) in plasmacytoid dendritic cells (pDCs). The key ODNs used for B cell activation are mainly Class B (e.g., ODN 2006, ODN 7909) and Class C (e.g., ODN 2395, C274), as these molecules act as TLR9 agonists, inducing polyclonal activation, proliferation, cytokine secretion (IL-6), and surface marker expression (CD80, CD86, CD25).
With respect to the general method of ex vivo or in vitro B cell stimulation, the art has recognized both antigen-dependent and independent methods for stimulating B cell populations. Antigen-dependent, which appears to be the method claimed herein, requires specific antigens to stimulate B-cell receptors (BCR), mimicking natural infection. The use of recombinant CD40 ligand (CD40L) combined with cytokines like IL-4, IL-2, and eventually IL-21 became the standard for expanding human B cells ex vivo, enabling the study of memory B cells and plasma cell differentiation. To overcome low efficiency, the art adopted innate signals such as TLR9 agonists (e.g., CpG ODN2006), which are highly potent in activating human B cells, often surpassing traditional mitogens. Current techniques, such as combinations involving IL-17+BAFF+CpG, are now used for high-throughput identification of antigen-reactive B cells from patients, aiming at personalized cancer immunotherapies and improved vaccine evaluation.
Current challenges to such methods are that while memory B cells are easily activated ex vivo, naïve B cells are more fastidious, making their expansion for studies on emerging pathogens technically difficult. Ex vivo stimulation of B cells from pathogen-naïve individuals is challenging because these cells are quiescent, lack pre-existing affinity-matured receptors, and require complex, multi-signal activation that is difficult to replicate outside the body. The process often results in poor proliferation, low-affinity antibody production, or immediate apoptosis rather than the necessary maturation into high-affinity memory cells. The B cell precursor frequency in naïve individuals to a new pathogen is extremely low, making it difficult to detect or expand them, as opposed to memory B cells which are easily activated. Naïve B cells typically require signals from CD4+ helper T cells (such as CD40L and cytokines) to initiate effective proliferation and immunoglobulin isotype switching, and replicating this T-cell dependent environment in vitro is technically difficult, meaning that most ex vivo stimulated B cells that do not acquire the necessary T cell support will not survive (Karagiannis P, et. al. Clin Exp Immunol. 2022 Jan 28;207(1):84-94.) Ex vivo systems often fail to mimic the complex 3D environment of secondary lymphoid organs where germinal centers (GCs) form, leading to a failure in producing high-affinity, class-switched antibodies. When stimulated, naïve B cells tend to differentiate rapidly into short-lived, low-affinity plasma cells rather than entering the germinal center pathway, which is necessary for long-term memory, and raises a question of timing when it comes to stimulation of B cells vs. re-introducing said cells back into the host. Another timing issue is with respect to the inability of the transferred, stimulated cells to find their target antigen, or by the rapid, premature elimination of these cells (Turner JS, et. al. Nat Commun. 2017 Apr 21;8:15072.) While Toll-like receptor (TLR) agonists like ODNs can activate B cells, they can sometimes block antigen processing, causing apoptosis or forcing the cells into a "metabolic clock" that restricts their ability to survive and differentiate properly. Naïve B cell populations are diverse, and inconsistent markers make it difficult to identify, isolate, and uniformly stimulate them, leading to contradictory results (Akkaya M, et. al. Nat Rev Immunol. 2020 Apr;20(4):229-238. Epub 2019 Dec 13.) Additionally, the age of the individual has a marked effect on whether or not ex vivo stimulated B cells can respond to new antigens (Ciocca M, et. al. Front Immunol. 2021 Jul 23;12:690534.) So while the art has provided methods for ex vivo or in vitro stimulation of B cells, especially naïve B cells, there are still significant hurdles and variables that are specific to the subject and antigen, making the experimentation regarding such methods non-routine, especially when it comes to then re-introducing said cells into the subject.
Working examples. The working example disclosed in the specification describes the isolation of peripheral blood mononuclear cells (PBMCs) from individuals who were not exposed to SARS CoV-2 antigen through vaccination or natural infection (¶[0020]). The cells were isolated using SIGMA's HISTOPAQUE 1083-1, stimulated with CpG (ODN 2006), and incubated overnight at 37°C with 5% CO2. SARS-related Coronavirus-2 isolate USA-CA1/202 was filtered and added to the wells with RPMI media, and allowed to incubate for 6 hours. B-cell markers were then added to the samples (¶[0021]) and overexpression of CD27 (memory B-cell marker) along with some B-cell activation markers (CD86, CD38, CD40) was noted post-viral infection (¶[0021]). Said B cells were not isolated and re-introduced back into the donor. Example 2 utilized PBMCs from 3 individuals who were not exposed to SARS CoV-2 antigen through vaccination or natural infection, and aliquots of white blood cells were incubated with reagents to support growth/survival of T or B cells over 7 days. Either formaldehyde-inactivated SARS CoV-2 virus or SARS CoV-2 peptides (mixture of SARS-COV-2 peptides consists of 15 mers with 11 amino acid overlapping peptides that cover the immunodominant sequence domains of the SARS-COV-2 Spike protein) were incubated with these cells for another 7 days. Changes in B cells populations in the peptide and inactivated virus-treated samples were noted (¶[0026-0032]). Again, these B cells were not then re-introduced back into the donor.
As previously noted, the methods of the instant claims are broadly claiming exposure of the cells ex vivo or in vitro to any antigen, which reasonably includes live, wild-type pathogens, inactivated pathogens, or live, attenuated pathogens. It is not clear that such a method would be considered safe by one of skill in the art, as the method does not indicate which specific pathogen is inactivated or live, attenuated, how it is inactivated/attenuated, nor does it require the removal of the pathogen from the ex vivo stimulated sample before re-introduction back into the subject. Both the specification and claims are drawn towards the use of live pathogens, as well as inactivated pathogens and peptides (see e.g. ¶[0003][0007][0016-0017]; Example 1). Further, as the isolated blood product is exposed to pathogen, it is not clear from the method steps that, after said exposure, the pathogen is removed from the sample before inoculation of the antibodies or plasma cells back into the host, thus reading on a method of inoculating the subject with live, wild-type pathogen. While certain populations can receive live, attenuated pathogens, many cannot, as their immune system is not sufficient or mature enough to keep the attenuated pathogen in check. The Office contends that, depending on the pathogen, good manufacturing practices would prefer the removal of any and all antigens, specifically live, attenuated pathogens, from the blood treatment sample before re-introducing said sample into the host, and it is not clear from the claim language or this specification and examples provided that the claimed methods are fully enabled.
Guidance in the specification. The actual guidance provided for in the examples is limited to isolating PMBC from SARS CoV-2 naïve subjects and exposure of said isolated PBMC, especially in the presence of ODN 2006, to a specific pool of SARS CoV-2 S protein peptides. The specification provides only prophetic guidance towards the use of any antigen from any source, especially any pathogen, live or inactivated, to stimulate immune cells ex vivo and then re-introduce said stimulated cells to the host in a method of autologous passive immunity or “in vitro vaccination”.
Amount of experimentation necessary. Extensive clarification as to the method steps and extensive additional research is required in order to determine how effective it would be to use any type of any broadly claimed antigen to stimulate any type of white-blood cell derived immune cells ex vivo, namely B-cells, with or without the presence of ODN, and then re-introduce said stimulated cells back into the same host from which they were taken. It is unclear if said method would indeed induce short term or long term protective immunity in said host, as it is unclear which type of immune cells would be re-introduced. It is unclear as to the specific timing of each step, as the art has shown that certain steps would be time-sensitive to ensure survival of any stimulated B cells. The art has also shown that the age of the donor of the PBMC would have an effect, and it is unclear if the method as claimed is only effective in healthy, young populations, or if it needs to be adjusted for those considered to be non-healthy or otherwise immunocompromised.
Finally, in light of the Supreme Court decision in Amgen Inc. et al. v. Sanofi et al., 143 S. Ct. 1243 (2023) (hereafter Amgen), updated guidelines were provided regarding the assessment of enablement (Federal Register, pp. 1563-1566; Pub. Jan. 10, 2024.) In Amgen, the Supreme Court unanimously affirmed that a genus of monoclonal antibodies were not enabled because when a range within a genus is claimed, there must be reasonable enablement of the scope of the range. The Court found in Amgen that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality. In the instantly claimed invention, there is an extraordinarily large genus of potential antigens (both source and type/format of antigen) that would need to be tested in the method, and the method has not definitively shown what steps are essential or required in order to perform said method safely and effectively, such as whether or not the “antigen” from the pathogen is cleared from the stimulated blood product before re-introduction back into a human subject. It would require further experimentation on the large genus of ODN to determine which ODN would be useful in the method as claimed, and for how long said PBMC would need to be exposed to said ODN. While a method does not have to be a laboratory protocol with specific, detailed minutiae claimed, there has to be sufficient enabled guidance provided for said claimed method either in the specification or in the prior art, and explanation to how to perform the claimed methods is lacking in both. Due to the large number of genera claimed (e.g. antigen source, form antigen may be in to stimulate blood product, blood product that is delivered back to host, B cell markers that must be up/down regulated to exhibit the desired stimulation, human subjects that could safely receive said products in said method, timing of B cell stimulation and re-introduction into the host, etc.), it would require a person of skill in the art a large amount of undue experimentation on their part from the limited guidance of the art and specification in order to get the claimed methods to work.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to perform the claimed methods.
Response to Arguments
While the previous enablement rejection has been withdrawn, a new scope of enablement rejection in light of the amendments to the claims has been raised. Therefore, arguments regarding the enablement of the claims will be addressed as applicable herein in the interest of compact prosecution.
Applicant argues that independent claims 1 and 6 have been amended to no longer be drawn to generic methods of stimulating immune cells in vitro or ex vivo through exposure to any live, attenuated or inactivated pathogen, then re-introducing said stimulated immune cells back into the patient. As such, independent Claims 1 and 6 should now contain subject matter 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. Applicant asserts no new matter has been added. While the original enablement rejection has been withdrawn, a new scope of enablement has been raised with respect to the narrowed claims for the reasons elaborated upon supra. Due to the breadth of certain limitations within the claimed methods and the knowledge of B-cell stimulation in the prior art, it remains that the breadth of the independent claims is not fully enabled. Therefore, Applicants arguments are not entirely persuasive, and the claims remain rejected.
Claim Rejections - 35 USC § 102
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 following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
(New rejection – necessitated by amendment.) Claims 6-7 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Reyes et. al. (Reyes RA, et. al. bioRxiv [Preprint]. 2021 Sep 27:2021.09.24.461732.; hereafter “Reyes”.)
The Prior Art
Reyes teaches analysis of peripheral blood mononuclear cells (PBMC) from healthy and SARS CoV-2 infected patients (p. 6, “Results: Study criteria”). Reyes teaches separating the B cells from the samples, and dividing said B cells further into naïve, unswitched memory, resting switched memory, activated switched memory, and double negative B cell subsets (p. 7, ¶1; Fig. 2A.) Cell surface markers, such as CD19, CD20, CD38, CD27, CD21, and IgD were utilized to aid in B cell separation (Fig. 2, p. 7, ¶1; instant claim 7). Further studies on these B cells was performed in the presence of SARS CoV-2 spike (S) protein antigens, namely full-length S and the receptor binding domain (RBD) of S (pp. 7-8, ¶ bridging pages, to p. 8, ¶2; Fig. 3.) After the B cells were stimulated with the SARS CoV-2 antigen cocktail (Table S2), they were gated using cell surface markers, such as CD38, IgD, CD27, CD80, Ki-67, CD95, and CD21 to determine the difference in B cell populations which were reactive to the antigens (Figs. 3-4; instant claims 6, 9).
For at least these reasons, Reyes teaches the limitations of instant claims 6-7 and 9, and anticipates the invention encompassed by said claims.
Conclusion
No claims are 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 RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671