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 .
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.
Claim Status
Applicant's arguments and amendments dated 2/9/25 have been received and entered in the application.
Claims 1, 3-4, 6, 10, 12, 14, 16, 20, 23-25, 27, 32-36, 38-49 are currently pending.
Claims 23-25, 27, 32-36, 38 are withdrawn as directed to non-elected inventions effectively without traverse in the response dated 12/27/23.
Claims 1, 49 are currently amended.
Claims 1, 3-4, 6, 10, 12, 14, 16, 20, 39-49 are elected and examined on the merits.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in this application. Any objections rejections not specifically reiterated are hereby withdrawn.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3-4, 6, 10, 12, 14, 16, 20, 39-47, 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ingber et al., US Publication No. 2011/0250585 (hereinafter Ingber). in view of Goyal et al., PCT Publication No. WO2018/017605 (cited on 892 dated 10/27/23, hereinafter Goyal).
Regarding claims 1, 6, 45, 49, Ingber discloses organ mimetic microfluidic devices and uses thereof (Abstract). Ingber discloses a system having a central microchannel (i.e., a cell culture chamber) separated via by porous membranes into two more parallel microchannels (i.e., one or more channels) ([0019], [0076]-[0095], Fig. 2). The membrane is preferably coated with at least one attachment molecule which promotes cellular adhesion ([0019], [0066], [0121]-[0124]). In some embodiments, the membrane may be designed to include patterns [0106],[0156]-[0159], Fig. 4). The patterns may be micro and/or nanoscopic patterns whereby “any parameter or characteristic of the patterns may be designed to desired sizes, shapes, thicknesses, filing materials, and the like” ([0106], Fig. 4). Preferably the membrane is coated on one or both sides of the membrane ([0132]). Any cells from a multicellular organism may be utilized in the device, including immune cells ([0132]-[0144]). Ingber explains that the disclosed systems may be useful for the study of complex organ functions and for testing of therapeutics ([0013], [0044]).
Regarding claim 3, Ingber discloses that the any cells from a multicellular organism may be utilized in the device, including combinations of cells ([0132]).
Regarding claim 4, Ingber discloses that the cells may be primary cells ([0124]).
Regarding claim 10, Ingber discloses that the membrane made of any polymeric compound or material, including silk and ECM gels ([0107], [0121]).
Regarding claim 12, Ingber discloses that the body of the device may be made of a flexible material, such as PDMS, or non-flexible materials, such as glass ([0076]).
Regarding claim 14, Ingber discloses that the system may include inlets from which fluid flows into the system and corresponding outlets ([0078]-[0087], Fig. 2).
Regarding claim 40, the membrane may be composed of any polymeric compound or material, including ([0107]).
Regarding claim 42, immune cells which may be present in the system include B cells, T cells, dendritic cells, macrophages, neutrophils, and combinations thereof ([0140]).
Regarding claim 46, Ingber discloses that the membrane may be made of any polymeric compound or material, ECM gels ([0107], [0121]). Ingber further discloses that membrane may be coated with cell adhesion substances or ECM proteins, such as collagen ([0121]-[0124], [0159]). Therefore, Ingber discloses that ECM proteins (e.g., collagen) may both be used as the membrane and as a coating disposed on the membrane.
Regarding claim 47, Ingber discloses that the membrane may be made of PDMS or ECM gels ([0107], [0121]).
Regarding claim 20, Ingber does not disclose, that the system may be a length scale model of a mammalian lymph node. However, Ingber explains that the device may be utilized to re-created lymph nodes which may be implanted in an animal model ([0065]). Therefore, there is a suggestion present in Ingber that the system may be scaled for a mammalian animal.
Regarding claim 41, Ingber does not disclose that the membrane may be composed of polyethylene glycol. However, Ingber discloses that the membrane may be composed of any polymeric compound or material, and that the specific materials utilized will depend on the particular material properties required ([0107]). Therefore, there is a suggestion present in Ingber, that a skilled artisan would be able to select an appropriate membrane material.
Ingber does not disclose that the immune cells are contained within a scaffold. Ingber also does not disclose that the cell culture chamber comprises a first zone comprising B cells surrounded by a second zone comprising T cells, or that the immune cells may be activated T cells or CAR-T cells.
Goyal discloses organ-on-a-chip microfluidic devices which mimic lymph nodes (Abstract). The device includes a body (housing) comprising one or more cell culture chambers and one or more microchannels in fluidic communication with the chamber ([0011]). The cell culture chambers further contain a matrix material, such as collagen, laminin, or Matrigel, containing the cells ([0011]-[0012]). In some embodiments, the device may include microdomains within the matrix to promote 3D organization of cells within the structure ([0012], [0076]). Goyal explains that the disclosed system are highly useful for testing the efficacy of various therapeutics ([0083]-[0088]).
Regarding claim 16, Goyal discloses that the device can include a circular microchannel and chambers, thus providing the ability to mimic compartmentalization and/or the radial gradients that can occur in the human lymphatic system ([0061], Fig. 4). The device may include a first chamber including B lymphocytes and a second chamber including T lymphocytes ([0011]-[0012]). The chambers may be separated by pillar arrays or membranes ([0061], Fig. 4).
Regarding claim 39, Ingber does not disclose that the membrane comprises a photo-reactive crosslinking group and/or a photoinitiator. However, Ingber discloses that the membrane may be composed of extracellular matrix gels with or without crosslinking ([0107]). As photo-crosslinking is one of a finite number of identified means for crosslinking of hydrogels, it would be obvious to one of ordinary skill in the art to try a photocrosslinkable hydrogel in the methods of Ingber with a reasonable expectation of success.
Regarding claim 43, Goyal discloses that the human lymphoid tissue-on-chip enables the study of chimeric antigen receptor (CAR) T cell therapy trafficking and expansion ([0087]).
Regarding claim 44, in some embodiments, the immune cells may be a T lymphocyte activated by treating the cell in vitro with a drug or therapy ([0080]).
As both Ingber and Goyal are directed to organ mimetic microfluidic devices and uses thereof, it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would be motivated to utilize the teachings of Goyal in the methods of Ingber to more accurately represent lymphatic tissue as Goyal indicates that one of ordinary skill in the art can easily construct useful combinations of cells in the device and that more modifications are possible than those explicitly disclosed by Ingber ([0132], [0181]).
Claim(s) 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ingber and Goyal as applied to claims 1, 3-4, 6, 10, 12, 14, 40, 42, 45-47, 49 above, and further in view of Lucas, S. B., (2017) Lymph node pathology in infectious diseases. Diag Histopath, 23:pp.420-430 (cited on 892 dated 1/8/25, hereinafter Lucas).
Regarding claim 48, the combination does not disclose that the lymph node is a certain type of lymph node.
Lucas reviews the typical lymph node histological features associated with common infectious agents and describes the effects of infection in different types of lymph nodes (Abstract). Lucas discloses how cervical lymph nodes are involved in lymphadenopathy in response to H. simplex infection and toxoplasmosis (pg. 420, right col., par. 5) and that mesenteric lymph nodes present acute reaction in response to gastrointestinal inflammation, including appendicitis and intestinal perforation (pg. 420, right col., par. 6). Lucas also discusses the role of mediastinal lymph nodes in increasing detection of lymph node involvement accompanying pulmonary disease via sampling of the draining lymph nodes (pg. 421, left col., par. 2). With Epstein-Barr virus, cervical nodes and tonsils are affected (pg. 423, left col., par. 2). Furthermore, Lucas discloses that assessing reactive patterns that support diagnosis of specific infections is important since lymph node reactions to infections have many common, reproducible components and particular combinations that can point to a specific agent even in the absence of demonstration of the infectious agents (Conclusions in pg. 430). The immune status of the patient results in variations of such reactions and molecular tests for identification and quantification of micro-organisms in formalin-fixed, paraffin-embedded tissues are insufficiently sensitive to reveal infection reliably (pg. 430, left col., par. 1). In summary, Lucas teaches that additional clinical, serological, microbiological and molecular diagnostic investigations, in response to recognition of suggestive pathology, are essential (abstract).
Accordingly, it would have been obvious to obtain any of the types of lymph nodes recited in instant claim 48 since the involvement of several of the different types of lymph nodes recited in claim 48 in response to different infectious agents was disclosed in the prior art, as taught by Lucas. One of ordinary skill in the art would have been motivated to obtain any of the types of lymph nodes recited in instant claim 48 with the purpose of investigating the lymph node’s reactive patterns in response to specific infectious agents so as to develop methods for better diagnosing specific infections, as taught by Lucas. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success in obtaining a lymph node model such as the lymph nodes recited in instant claim 48.
Response to Arguments
Applicant’s arguments and amendments dated 2/9/26 have been fully considered but are moot in part and not persuasive in part due to the new grounds of rejection necessitated by applicant’s amendments. To the extent that the arguments are pertinent to the current grounds of rejection they are responded to below.
Claim(s) 1, 3-4, 6, 10, 12, 14, 16, 20, 39-47, 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ingber in view of Goyal.
Applicant argues that the devices of Ingber are based on 2D membranes which cannot be used to encapsulate cells in a 3D culture (Response p12).
In response, the combination discloses a microfluidic device in which cells may be encapsulated within a matrix material (Goyal [0011]-[0012]). Therefore, the combination of references is deemed to obviate the claims as presented.
Applicant argues that there is no teaching or suggestion of a user-defined 3D spatial pattern formation (Response p12). Applicant argues that Goyal relies on self-organization (Response p12-13).
Each of Ingber and Goyal disclose that a scaffold material may be patterned such that defined 3D structures are present (See e.g., Ingber [0106],[0156]-[0159], Fig. 4, Ingber [0012], [0076]). Therefore, the combination of references is deemed to obviate the claims as presented.
Claim(s) 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ingber, Goyal, and Lucas.
Applicant argues that there is nothing present in Ingber that would invite one of ordinary skill in the art to obtain any of the recited types of lymph notes without trial and error experimentation (Response p14).
It must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). The combination explains that the disclosed systems may be advantageous for multiple applications, including assessing efficacy of various therapeutics (See e.g., Goyal [0083]-[0088], Ingber [0013], [0044]). Lucas explains that specific types of lymph nodes are known to allow for better assessment of the lymph node’s reactive patterns. Therefore, there is a suggestion present in Lucas to utilize certain lymph node types.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 KARA D JOHNSON whose telephone number is (571)270-1414. The examiner can normally be reached Monday-Friday 8:00-4:00 CT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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