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 .
Status of the Claims
Claims 38-57 are pending in the application and are the subject of this office action.
Election/Restrictions
Applicant’s election without traverse of a lipoprotein in claim 48, a protein in claim 49, and an immune cell in claim 51 in the reply filed on 17 April 2026 is acknowledged.
Priority
The instant application is a 371 National Stage of PCT/GB2022/050671, filed 16 March 2022. The instant application claims benefit of foreign application GB2103609.0, filed 16 March 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 15 September 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Interpretation
It is noted that claim limitations that are presented as optional (e.g. “optionally wherein”) throughout the claims are not limiting to the claim and do not distinguish the claim over the prior art. Limitations presented as optional are explicitly not required, and therefore the claim still encompasses embodiments which do not meet these limitations.
Regarding the term “reference panel” it is noted that the specification provides: The test panel and the reference panel are correlated such that results of interrogation of the test panel and selection of desirable characteristics may result in selection of the corresponding reference microdroplet containing at least one cell. Thus, the results from interrogation of the test panel may be correlated to the progenitor cell and the same is selected (Pg. 6, Ln. 24-27). At least one microdroplet panel can be reserved as a reference panel, and at least one other panel can be used in the method of the invention (“test panel”). The reference panel and the test panel therefore contain corresponding or correlating cells, and results from the test panel can result in identification of its corresponding cell in the reference panel. It may be described that the test panel of microdroplets and the reference panel of microdroplets each contain cells derived from the original progenitor cell, and therefore are genetically identical or are clones (Pg. 7, Ln. 15-16). According to any embodiment, the results obtained from the assays on the test panel of microdroplets can be directly correlated to cells in the reference panel; such that it is cells from the reference panel that are selected (Pg. 38, Ln. 34-37).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 38-57 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 38 is rejected as indefinite because the claim recites an abbreviation that is not spelled-out in its first use in the claims (i.e. EWOD, oEWOD). Since the meaning of these abbreviations is unclear, the scope of the claim is unclear. Clarification is required.
Claim 38 is rejected as indefinite because the preamble of the claim is inconsistent with the body of the claim. The preamble recites a “method for selecting cells and/or part(s) of a cell” but the body of the claim only recites selection of cells. There is no recitation in the independent claim or any of its dependent claims regarding the selection of parts of cells. It is not clear how one would select parts of a cell based only on the method steps recited in the claims.
Claim 38 is rejected as indefinite over the recitation “detecting a change in said reporter entity based upon the presence of at least one characteristic” and “selecting a subset of microdroplets from a panel on the basis of the change in the reporter entity” wherein the limitation, and specifically the phrasing “based on” (or “on the basis of”) does not create a clear or defined relationship between detection of a change in the reporter entity and the presence of at least one characteristic or the selection of a subset of microdroplets. Claims 42 and 45 are rejected for the same reasons.
Claim 38 is rejected as indefinite over the recitation “a test panel of microdroplets comprising at least a medium or a medium and at least one cell” (step i) and “selecting a subset of microdroplets from a panel on the basis of the change in the reporter entity, said subset containing the selected cells” (step v). The recitation of the generic “a panel” is unclear in this context because there is introduction of multiple specific panels in the claim (e.g. a test panel, a reference panel, a reporter panel). As such, it is unclear whether generic recitation of a panel refers to one of these specific panels, any of these specific panels, or a different panel entirely. Additionally, if the generic “panel” is interpreted to refer to the test panel or the reporter panel, this is unclear because neither the test panel nor the reporter panel are specifically required to contain cells (i.e. the step I explicitly states that the test panel may comprise only medium), such that it is not clear how one could select a subset of microdroplets containing cells from these panels. If the generic “panel” is interpreted to refer to the reference panel introduced later in the claim, this is unclear because there is no clear or recited relationship between the monitoring step, the change in the reporter entity, and the reference panel. Clarification is required.
Claim 38 is rejected as indefinite because the relationship between the limitations in the last two paragraphs of the claim is unclear and confusing. It is not clear whether the step of the last paragraph replaces the step of the previous paragraph, or whether it is an additional step. This is additionally confusing because both paragraphs refer to the formation of a test panel which is used in step i., but the step of the last paragraph is recited to occur before or after any of steps i-v. Additionally, the recitation of multiple different test panels within the last paragraph is confusing, because the phrase “test panel” appears to simultaneously refer to both the parent panel and the child panel created by splitting the parent panel, and it is further unclear which of these panels is the “test panel” referred to in steps i-v. Additionally, if the splitting recited in the last paragraph is potentially performed before and after all of steps i-v, this would result in the creation of many different test panels, and it is unclear which of these panels in particular is the “test panel” recited in steps i-v. Clarification is required.
The limitation “suitable for merging with microdroplets of a reporter entity panel” in the last paragraph of claim 38 is unclear and renders the claim indefinite because neither the context of the instant claims nor the specification clarifies what particular features or requirements make a microdroplet suitable for merging with microdroplets of a reporter entity panel, and as such the metes and bounds of the limitation are unclear.
The recitation of a “reporter entity panel” in the last paragraph of claim 38 is unclear and renders the claim indefinite because it is not clear whether “reporter entity panel” refers to the same “reporter panel” introduced in step ii of the claim, or whether this refers to a different panel altogether. Clarification is required.
The term “change” in claims 38, 42, 45, and 50 (i.e. in step iv. detecting a change in said reporter entity) is a relative term which renders the claim indefinite. The term “change” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The detection of a change in a reporter entity appears to require an ability to distinguish between some baseline characteristic or state of the reporter entity and an alteration to that baseline, however, no such baseline of a reporter entity is established in the claims, and as such, the metes and bounds of what might or might not comprise a change in the reporter entity is unclear.
In claim 40 the recitation “wherein prior to splitting the panel of microdroplets containing at least one cell” is unclear and renders the claim indefinite. Claim 38 recites multiple different panel of microdroplets which may be split at multiple different points throughout the method, as such it is not clear which panel is the subject of this recitation in claim 40 and the limitations of the phrase “prior to” in this context are unclear. Clarification is required.
In claim 42, recitation of “the panel of microdroplets” is unclear. There is prior introduction of multiple different panel of microdroplets, such that it is unclear exactly which one the generic “the panel of microdroplets refers to.
Claim 44 is vague regarding “the selected panel of microdroplets”. There is no prior introduction of “a selected panel of microdroplets” therefore there is insufficient antecedent basis for this limitation in the claim.
Claim 44 is rejected as indefinite because the metes and bounds of the claim are unclear due to the recitation “including, but not limited to”.
Claim 46 is rejected as indefinite because a plurality of cells are previously introduced in the claim, such that it is unclear which particular cell the recitation “the cell is genetically engineered” refers to.
Claim 47 is rejected over the phrasing “may be” which renders it unclear whether or not the limitations that follow are required in order to meet the claim.
Claim 56 is rejected as indefinite because a plurality of cells are previously introduced in the claim, such that it is unclear which particular cell the recitation “said cell” refers to.
Claim 57 is rejected as indefinite because the claim is confusing and the meaning of the limitations is unclear. Specifically “wherein step (v) is a detection of multiplex assay” is confusing because it is not clear what is means to detect a multiplex assay within the context of step v which recites selecting a subset of microdroplets. Clarification is required.
Dependent claims 39-57 are rejected as indefinite because they depend from an indefinite claim and fail to remedy its deficiencies.
Subject Matter Free of Prior Art
Claims 38-57 are rejected as described above, but appear to be free of the prior art, as best interpreted in view of the 112(b) rejections discussed above.
The closest prior art is Weitz et al (US 2009/0068170 A1).
Regarding independent claim 38, Weitz teaches:
A method for selection cells and/or parts of a cell based on at least one characteristic in an EWOD or oEWOD device, the method comprising (Abstract: techniques for screening or sorting fluidic droplets which may contain cells, for example, cellas able to secrete species such as antibodies:
providing a test panel of microdroplets comprising at least a medium or a medium and at least one cell (Par. 6; Par. 45: cells may be encapsulated in the plurality of fluidic droplets; Par. 93: methods may be conducted for several droplets arranged in an array);
providing at least one reporter panel of microdroplets containing one or more reporter entities; merging microdroplets of the test panel with microdroplets of the at least one reporter panel to form a panel of merged assay microdroplets (Par. 111: controlled fusion of droplets containing beads and droplets containing cells; Par. 112: a droplet comprising a cell and a signaling entity may be fused with another droplet comprising a second signaling entity; Par. 74); and
selecting a subset of microdroplets from a panel on the basis of the change in the reporter entity, said subset containing the selected cells (Par. 7: determining a characteristic of a species present within a fluidic droplet using a signaling entity comprising a microparticle and an agent immobilized to the microparticle and able to bind the species; Par. 9: at least partially separating the fluidic droplets containing the cells able to secrete the species from fluidic droplets containing cells not able to secrete the species).
Weitz teaches that the method may comprise manipulation of droplets via a number of different droplet operations, including droplet splitting, but does not explicitly teach the method wherein the test panel of microdroplets is created by splitting a panel of microdroplets, further creating a reference panel of microdroplets, and/or wherein the test panel of microdroplets are split into at least two panels of microdroplets, said panels being a test panel and a reference panel.
Wheeler et al (US 2013/0143312 A1), Pollack et al (US 2009/0155902 A1), Pamula et al (US 2007/0243634 A1), and Srinivasan et al (US 2007/0275415 A1) are also noted as close prior art, all of which teach variations of detection and selection assays performed on microdroplet-encapsulated cells which are merged with reagent-containing microdroplets (see, e.g. Abstracts of each reference). However, like Weitz, they do not specifically teach the method wherein the test panel of microdroplets is created by splitting a panel of microdroplets, further creating a reference panel of microdroplets, and/or wherein the test panel of microdroplets are split into at least two panels of microdroplets, said panels being a test panel and a reference panel.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLIS LUSI whose telephone number is (571)270-0694. The examiner can normally be reached M-Th 8am-6pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached at (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677
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