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 .
Election/Restrictions
Applicant’s election without traverse of Group II (claims 36-38, 40, 41, 43, 46 and 47) in the reply filed on 10/22/2025 is acknowledged.
Claims 1-2, 4-12, 14, 36-38, 40-41, 43 and 46-47 are pending.
Claim 1-2, 4-12 and 14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group, there being no allowable generic or linking claim.
Claims 36-38, 40-41, 43 and 46-47 are examined on the merits.
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.
Claims 36-38, 40, 43 and 46-47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wagar et al (Nature Medicine (2021)27;125-135, as cited in the IDS filed 04/18/2023).
The applied reference has a common inventors/authors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1). This rejection under 35 U.S.C. 102(a)(1) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Regarding claims 36, 43: The claim recites “lymphoid organoid”. The term lymphoid organoid is interpreted as an in vitro cluster of cells comprising lymphoid cells.
Wagar teach a method of generating organoids from tonsil tissue for which said organoids recapitulate key germinal center features (abstract, p125 col2 ¶2). Wagar teach the organoids comprise T cells (Fig 1b). Because organoids are organized into organ-like or tissue-like structures, organoids that comprise T cells read on comprising aggregate of T cells.
Wagar further teach (a) plating cells (placing in a media) from tonsil tissue (lymphoid cells) results in clustered cells after several days of in culture (p126 col1 ¶1). Cells from tonsil tissue reads on obtaining cells from a subject.
Wagar further teach an antigen is plated (introduced) with the cells (p126 col1 ¶1). Cells are assessed after 7 days, this reads on incubating lymphoid organoid with said antigen (p126 col1 ¶1, Fig 1a). Wagar also teach the organoids are stimulated with antigen to produce antibodies against the antigen (Flu-specific IgG) (Fig 1c).
Wagar further teach isolating (purifying) the antibodies from the culture supernatants using an affinity column (p138 col1 ¶1).
Regarding claim 37: Wagar teach cells were plated from cryopreserved tonsil cells which were cultured with B cell activating factor (BAFF) in the medium (p136 col1 ¶5). BAFF in the media reads on introducing a B-cell activating factor to said media.
Regarding claims 38 and 40: Wagar teach stimulation of organoids with antigen with and without adjuvant (p133 col1 ¶3). This reads on introducing an adjuvant to said media and incubating the lymphoid organoid with the antigen and adjuvant because stimulation of an organoid requires incubation with the stimulating factor.
Regarding claims 46-47: Wagar teach the antigen is attenuated influenza vaccine (LAIV) (p126 col1 ¶1).
Thus the teachings of Wagar anticipate the invention as claimed.
Claims 36, 38, 40-41, 43, and 46-47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al (US 2005/0191743 A1).
Regarding claim 36: Wu teach a method of culturing peripheral lymphoid organoids which comprises the active steps recited by the instant claim. Wu teach culturing peripheral lymphoid organ cells on a scaffolding which is covered or surrounded with culture medium, wherein cells in the culture have cell to cell contact in three dimensions (abstract, claim 1). This reads on step a. of the instant claim; culturing lymphoid cells in media requires placing cells in media to produce said lymphoid organoid. While Wu do not use the term “organoid”, Wu teach hemopoietic cells grown in clusters (Fig 2A, p4 col2 [0027]) which reads on lymphoid organoids.
Wu also teach the culture medium contains antigens (claim 6). This reads on step b. introducing an antigen to said media because a medium comprising an antigen must have the antigen introduced to the media.
Wu teach incubating the 3D cultures (organoids) with antigen (LPS) (Example 3 p22 [0117]). This reads on step c. of the instant claim 36.
Wu also teach recovering monoclonal antibodies from cells derived from the lymphoid organoid (claim 36 of Wu). Recovering antibodies reads on step d. of the instant claim; isolating antibodies from the lymphoid organoid.
Regarding a germinal center and an aggregate of T cells; the “wherein” clause of the instant claim 36 following the active steps describes qualities of the lymphoid organoids, but does not require active steps.
Wu do not use the term “organoid”, however Wu teach hemopoietic cells grown in clusters (Fig 2A, p4 col2 [0027]), which reads on lymphoid organoids.
While Wu do not explicitly address a germinal center or aggregate of T cells as recited by the “wherein” clause of step a. of the instant claim, Wu does teach the claimed steps of the invention. Wu teach culturing peripheral lymphoid organ cells (total splenocyte preparations; example 2 p12 [0112]), which comprise B cells and T cells, and furthermore, Wu detect both B lymphocytes and T cells in the cultures (p13 [0115]), and the cells form a cluster, i.e. organoid, thus, the cluster of lymphoid organ cells reads on a germinal center and aggregates of T cells as it is considered that they are inherent to the cluster of Wu.
Regarding claims 38, and 40-41: The teachings of Wu are discussed supra. Wu also teach introducing an adjuvant (claim 26). Wu also teach culturing (incubating) with an antigen and an adjuvant (claims 24 and 26). Wu also teach introducing the adjuvant after introducing the antigen (claim 26).
Regarding claim 43: Wu teach obtaining spleen derived cells from a subject (mouse) (p12 [0112]).
Regarding claims 46-47: Wu teach the antigen can be a protein such as a tumor antigen (p9 [0080]).
Thus the teachings of Wu anticipate the invention as claimed.
Claim Rejections - 35 USC § 103
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 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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Wagar et al (Nature Medicine (2021)27;125-135; as cited in the IDS filed 04/18/2023) as applied to claims 36-38, 40-41, 43, and 46-47 above, and as discussed below.
Wagar et al. anticipate the subject matter of claims 36-38, 40-41, 43, and 46-47 and thus render the claims obvious (see above).
Regarding claim 41: Wagar teach stimulus with the PE antigen and introduction of an adjuvant (p133 col1 ¶4; Fig 6c). Wagar does not teach that the adjuvant is introduced after the antigen.
However, it would have been prima facie obvious to a person skilled in the art to add the adjuvant after introduction of the antigen and one would have a reasonable expectation of success.
With respect to the order of steps, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. Therefore, absent evidence to the contrary, it is obvious to perform the steps of the cited prior art in any order.
Thus the teaching of Wagar render obvious the invention as claimed.
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over Wu et al (US 2005/0191743 A1) as applied to claims 36, 38, 40-41, 43, and 46-47 above, and further in view of Purwada et al (Nature Protocols (2017)12:1;168-182).
Wu et al. teach the subject matter of claims 36, 38, 40-41, 43, and 46-47 (see above).
Regarding claim 37: The teachings of Wu are discussed supra. Wu do not teach introducing B cell activating factor.
Purwada teach methods to generate immune organoids ex vivo (abstract). Purwada further teach B cell activating factor (BAFF) is a prosurvival signal for B cells (p168 col1 ¶1). Purwada teach BAFF is introduced in the culture via secretion by 40LB cells (p168 col1 ¶2, Fig 1).
It would have been obvious to one of ordinary skill in the art to adapt the methods of Wu drawn to generating antibodies from a lymphoid organoid by introducing a B-cell activating factor to the media as taught by Purwada.
One of ordinary skill in the art would have been motivated to modify the method as taught by Wu by introducing B-cell activating factor, as taught by Purwada to for the purposes of increasing B cell survival.
One would have had a reasonable expectation of success because B-cell activating factor is known in the art to improve B-cell survival and Purwada successfully generates lymphoid organoids with the inclusion if BAFF in the culture.
Thus the teachings of Wu and Purwada render obvious the invention as claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 36-38, 40-41, 43 and 46-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 27 of copending Application No. 18/726,384 (reference application, herein referred to as ‘384 ) in view of Wu et al (US 2005/0191743 A1), Purwada et al (Nature Protocols (2017)12:1;168-182), Christensen et al (Human Vaccines & Immunotherapeutics (2016)12:10;2709-2711), Lewis et al (Sci Immunol (2019)4:33;1-25) and Michaud et al (OncoImmunology (2014)3:9;1-8).
Although the claims at issue are not identical, they are not patentably distinct from each other (see below).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 36: The instant claim is drawn to a method for generating antibodies from a lymphoid organoid. Copending claim 27 of ‘384 is also drawn to a method for generating antibodies from a lymphoid organoid.
MPEP (2111.02 II) states “During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim”.
Claim 27 of ‘384 teaches the identical active method steps as the instant claim 36. Claim 27 of ‘384 teaches step a. placing lymphoid cells in a media to produce a lymphoid organoid. This reads on step a. of the instant claim. ‘384 teaches step b. introducing an antigen to the media. This reads on step b. of the instant claim. ‘384 teaches step c. incubating the lymphoid organoid with the antigen to generate antibodies. This reads on step c. of the instant claim. Claim 27 of ‘384 also teaches step d. isolating the antibodies from the lymphoid organoid. This reads on step d. of the instant claim.
Regarding claims 38, and 40-41: The teachings of ‘384 are discussed supra. ‘384 does not teach introducing an adjuvant, incubating the lymphoid organoid with the adjuvant, or introducing the adjuvant after the antigen.
Wu teach introducing an adjuvant (claim 26). Wu also teach culturing (incubating) with an antigen and an adjuvant (claims 24 and 26). Wu also teach introducing the adjuvant after introducing the antigen (claim 26).
It would have been obvious to modify the method of ‘384 , drawn to a method for generating antibodies from a lymphoid organoid, with the teachings of Wu, to introduce an adjuvant with an antigen (or an adjuvant after introducing the antigen) and culturing cells with said antigen.
One would have been motivated to introduce an adjuvant with an antigen (or after introducing the antigen) and culturing cells with said antigen because Christensen teach vaccine adjuvants can increase and modulate the immunogenicity of a vaccine (antigen) and are added to make a vaccine (antigen) more immunogenic and therefore more effective (abstract).
One would have had a reasonable expectation of success because Christensen teach adjuvants have been used for over 60 years (p2709 col1 ¶2) and as such, are well characterized in the art.
Regarding claim 43: The teachings of ‘384 are discussed supra. ‘384 does not teach obtaining cells from a subject where the cells are derived from spleen tissue.
Wu teach obtaining spleen derived cells from a subject (mouse) (p12 [0112]).
It would have been obvious to modify the method of ‘384 , drawn to a method for generating antibodies from a lymphoid organoid, with the teachings of Wu, to use cells derived from spleen tissue because Lewis teach the spleen is the largest secondary lymphoid organ in the body (abstract).
It would have been obvious to modify the teachings of ‘384 , drawn to a method for generating antibodies from a lymphoid organoid, with the teachings of Wu, to obtain spleen derived cells from a subject, because Lewis teach the spleen is the largest secondary lymphoid organ in the body. One of ordinary skill in the art would understand that a large organ would represent an efficient source of cells.
One would have had a reasonable expectation of success because Wu successfully use cells from spleens to generate hemopoietic cells grown in clusters (Fig 2A, p4 col2 [0027]), which reads on lymphoid organoids.
Regarding claims 46-47: The teachings of ‘384 are discussed supra. ‘384 does not teach the antigen is a cancer related protein.
Wu teach the antigen can be a protein such as a tumor antigen (p9 [0080]). Michaud teach tumor antigen targeting monoclonal antibody-based treatments are considered to be one of the most successful strategies in cancer therapy (abstract).
It would have been obvious to one of ordinary skill in the art to combine the teachings of ‘384, drawn to a method for generating antibodies from a lymphoid organoid, with the teachings of Wu, using a tumor antigen, because Michaud teach tumor antigen targeting antibody-based treatments are successful strategies in cancer therapy.
One would have had a reasonable expectation of success because the disclosures are drawn to methods of generating antibodies.
Regarding claim 37: The teachings of ‘384 and Wu are discussed supra. Wu do not teach introducing B cell activating factor.
Purwada teach methods to generate immune organoids ex vivo (abstract). Purwada further teach B cell activating factor (BAFF) is a prosurvival signal for B cells (p168 col1 ¶1). Purwada teach BAFF is introduced in the culture via secretion by 40LB cells (p168 col1 ¶2, Fig 1).
It would have been obvious to one of ordinary skill in the art to adapt the methods of ‘384 and Wu, drawn to generating antibodies from a lymphoid organoid by introducing a B-cell activating factor to the media as taught by Purwada.
One of ordinary skill in the art would have been motivated to modify the method as taught by ‘384 and Wu by introducing B-cell activating factor, as taught by Purwada to for the purposes of increasing B cell survival.
One would have had a reasonable expectation of success because B-cell activating factor is known in the art to improve B-cell survival and Purwada successfully generates lymphoid organoids with the inclusion if BAFF in the culture.
Thus the disclosures of ‘384 , Wu, Purwada, Christensen, Lewis and Michaud render obvious the invention as claimed.
Conclusion
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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/TAEYOON KIM/Primary Examiner, Art Unit 1631