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 .
This office action is in response filed 2/19/2026.
Claims 1-16 are pending.
This application is a division of U.S. Patent Application No. 15/027,471 filed on April 6, 2016, now U.S. Patent 11,396,012, which is a National Phase of PCT Patent Application No. PCT/IL2014/050889 having International Filing Date of October 7, 2014, which claims the benefit of priority under 35 USC §119(e) of U.S. Provisional Patent Application No. 61/887,457 filed on October 7, 2013.
The priority of the claims has been evaluated by reviewing the priority documents. Applicants have argued that the limitations are found in the PCT application and a thorough search identified the limitations hence, claims 3, 5, 7, 10-12 and 14-16 are supported by U.S. PCT/IL2014/050889 having International Filing Date of October 7, 2014. Claims 1, 2, 4, 6, 8 and 13 are supported by the provisional application.
Response to Amendments
The amendments to the disclosure are sufficient to overcome the objections to the specification. The amendments are sufficient to overcome the rejection under 35 USC 112, second paragraph.
Claim Objections
Claims 1 and 9 are objected to because of the following informalities: these are new observations. Claim 1 recites --a surface of at least a portion of said test chamber—which is fairly redundant. The test chamber has surfaces that should inherently be a portion of the test chamber. It would be remedial to recite simply –wherein a surface of said test chamber--.
In claim 9, the abbreviation (R) should be provided in the first occurrence of hydrodynamic resistance and then used when referencing that term thereafter.
Appropriate correction is required.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first
paragraph, as failing to comply with the written description requirement. The claim(s) contains
subject matter which was not described in the specification in such a way as to reasonably
convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the
inventor(s), at the time the application was filed, had possession of the claimed invention. This rejection is maintained.
The disclosure appears to describe a device comprising a flow through channel also
called a flow through chamber. Further connected are a number of microchannels (which appears
to also be called thin capillaries) that connect the flow through channel to a test chamber. The
two, the microchannel with a test chamber, are called a reaction unit. (Labels added)
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The design of the claims is to allow for diffusion time to be shorter than flow time. The
specification suggests the diffusion is affected by length of the capillary channel length (also
called microcapillary or tiny capillary throughout the disclosure).
[0101] FIGS. 8A-D. GFP calibration and diffusion into the compartments. (A)
Calibration of the concentration of GFP expressed in the microfluidic chamber.
Fluorescent intensity measurements verses protein concentrations. (B) Measurement of
GFP diffusion time along the capillary from the flow channel up to the chamber as a
function of capillary channel length.
FIG. 8B
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Applicants have amended the claims to provide dimensions and these are presumed to provide diffusion to and from the microchannel (see ¶0102 and figure 5). However, there is no discussion of dimensions or conditions for flow except to say that
[0138] According to a particular embodiment, the hydrodynamic resistance of the microchannel is at least 5 or 6 orders of magnitude higher than in the flow-through channel. This reduces the flow in the microchannel by 5 or 6 orders of magnitude compared with the flow in the flow chamber. Furthermore, in the case where the microchannel is connected to the flow channel in one point only, there is no pressure gradient along the micro-channel and therefore there is no flow.
Secondly, claim 4 requires that a protein gradient is formed. The disclosure as above
teaches that this is because of the dimension of the device.
[0028] According to some embodiments of the invention, the device is
of dimensions such that the polypeptide expressed from said nucleic acid forms
a gradient in said reaction chamber.
[0124] The dimensions of the device were such that proteins expressed in the DNA
compartment generated gradient profiles with essentially no flow in the region.
The gradients were created by diffusion of the expressed proteins from the DNA
compartment and into the thin capillary. The thin capillary is connected to a flow through chamber, through which the nutrients and enzymes necessary for expression are continuously flowed. The device was designed in such a way that, in spite of the perfusion flow through the flow-through chamber, there was no flow in the regions where the gradient profiles were established.
The disclosure does not describe these dimensions. Without this information, it is not possible to formulate the device so that the gradients can form.
Third, claim 9 requires a hydrodynamic resistance of the microchannel that is 105 times
greater than that of the flow channel. This is also a function without a structure. The specification
teaches how to measure the hydrodynamic resistance but not how to ensure the structure has this
property.
[0134] According to a particular embodiment, the hydrodynamic resistance of the
microchannel is at least 5 or 6 orders of magnitude higher than in the flow-through
channel. This reduces the flow in the microchannel by 5 or 6 orders of magnitude
compared with the flow in the flow chamber. Furthermore, in the case where the
microchannel is connected to the flow channel in one point only, there is no pressure
gradient along the micro-channel and therefore there is no flow.
[0135] For a channel with length L, height h, width W and with a fluid with viscosity n
the hydrodynamic resistance is given by
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It appears that a difference in resistance is created by a difference in depth ratio.
[0139] Resistance of fluid flow through the reaction unit is higher than the resistance in
the flow-through channel. This resistance is typically established by having reaction units
that are substantially and sufficiently shallower and/or narrower than the adjacent flow-
through channels to create resistance such that there is essentially no flow in the reaction
unit. Such parameters can be readily determined by one of ordinary skill in the art using
mathematical or empirical modeling. According to a particular embodiment, the depth
ratio of the reaction unit:flow-through channel is greater than 1:5. Exemplary ratios
include 1:5, 1:6, 1:7, 1:8, 1:9, 1:10 and 1:20.
However, this will not meet the requirements of claim 9 that the difference is at least 10⁵ times
greater.
Hence, the specification teaches a functional requirement of the device but does not
describe how the property is met. To this end, the MPEP provides such guidance (emphasis
added). If the application as filed does not disclose the complete structure (or acts of a process)
of the claimed invention as a whole, determine whether the specification discloses other relevant
identifying characteristics sufficient to describe the claimed invention in such full, clear, concise,
and exact terms that a skilled artisan would recognize applicant was in possession of the claimed
invention. For example, if the art has established a strong correlation between structure and
function, one skilled in the art would be able to predict with a reasonable degree of confidence
the structure of the claimed invention from a recitation of its function. Thus, the written
description requirement may be satisfied through disclosure of function and minimal structure
when there is a well-established correlation between structure and function. In contrast, without
such a correlation, the capability to recognize or understand the structure from the mere
recitation of function and minimal structure is highly unlikely. As the invention is not adequately
described, the claimed method cannot be performed. Consequently, there is no evidence that
Applicant had conception or possession of the method being claimed.
Response to Arguments
Applicants’ amendments are not sufficient to overcome the rejection fully under 35 USC 112, first paragraph. First, there is no indication that flow is defined by dimension in the disclosure. The only factor that is used to define flow is that there must be more than one reaction unit or there is no flow.
[0144] In the case of a single reaction unit, with only one connection to the flow channel, there is no pressure gradient along the microchannel thus there is no flow. In the case of two compartments that are connected by a micro channel in parallel to the flow-channel, there are two points of connection between the main channel and the microchannels. In this case there is a pressure gradient along the microchannel, however diffusion time of a molecule along the microchannel is still shorter than the flow time along the microchannel.
This would allow for it to be longer than diffusion as no flow is longer than any diffusion. However, it is clear that the device requires more than one reaction unit attached to the flow through channel. Hence, it is not clear how the flow time i s modified by dimension given that the disclosure does not provide for this factor.
Secondly for both claim 4 and claim 9, the properties are functional as recited. It appears that the structure recited in claim 1 is all that provide for these functions and hence claim 4 and 9 lack description other than what is recited in claim 1.
Conclusion
Claims 7 and 9 are free of the art as the art does not teach use of tissue specific promoters in such methods where compositions are used in microfluidic devices for expression of peptides and the use of the hydrodynamic resistance is not shown in the art to lead to resistance in a microchannel that is 105 higher than the flow channel.
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 MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached on 8 am - 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARIA MARVICH/ Primary Examiner, Art Unit 1633
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