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 .
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.
Claim(s) 1-3, 5, 6, 8-11, 13-18, 22-28, 30, 32, and 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 2022/0047810 (“Park”) in view of in view of U.S. Patent No. 5,011,472 (“Aebischer”), “Control of Gene Expression Using a Red- and Far-Red Light-Responsive Bi-Stable Toggle Switch” (“Muller”), U.S. Publication No. 2022/0325240 (“McFarland”), and U.S. Publication No. 2014/0186850 (“Berniac”).
Regarding Claims 1, 6, 13-18, 22-23, and 26-27 Park discloses a hybrid bioelectric device (100) containing engineered cells for delivery of a therapeutic agent to a subject (Abstract).
Park fails to disclose that the device is “wearable”, but rather suggests that it “may be implanted” (Par. 48). However, Aebischer discloses a similar bioreactor device (20) which likewise comprises a source of engineered cells (30) which are configured to produce a therapeutic agent for delivery to a subject (Abstract). Aebischer discloses that this device could be implanted or provided “worn extracorporeally” (Abstract, Col. 5). It would have been obvious for one having ordinary skill in the art at the time the invention was made to configure the system of Park to be worn, instead of implanted, as disclosed by Aebischer, as an obvious design choice. While Aebischer fails to explicitly disclose any particular or specific benefits to extracorporeal devices versus implanted, the prior art does establish the two configurations to be suitable alternatives to one another, whereby it has been held that simple selection between two particularly recognized alternatives is obvious, requiring only routine and customary skill in the art, see KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007). Furthermore, Examiner notes that the ordinary artisan being a person of ordinary knowledge and creativity would be able to immediately recognize and appreciate various particular benefits to an extracorporeal system versus an implanted system which would flow naturally from such a substitution. For example, an extracorporeal device would eliminate the need for an expensive and invasive surgical procedure to implant the device, would allow the device to be more easily replaced or serviced without surgical revision, would allow the device to be made using different materials and different engineering standards simplifying construction and reducing costs, would allow the device to be larger…etc. Any of these benefits which would be immediately appreciated by the ordinary artisan without express suggestion, directly by the prior art constitutes a sufficient motivation to consider modification of the device of Park to be wearable. Furthermore, Examiner notes that Park, in reciting the device to be implantable, uses the indefinite “may”, i.e. a term used to indicate a possibility or probability. As such, it must be understood that Park does not believe this to be a critical and necessary feature, but rather an optional feature which some clinicians might find desirable, but may be eschewed by others without necessarily departing from the aims and goals of the invention.
Park discloses the device to comprise:
A cell cartridge (120) containing at least one type of engineered cells, wherein each of the engineered cells contains an optogenetic system (Abstract; Par. 15, 51) wherein each engineered cell is configured to produce at least one type of therapeutic agent in response to a first light having a first wavelength (Par. 15, 51, 55, 79);
An optical stimulating system (110) disposed adjacent to the cell cartridge (see Fig. 1), wherein the optical stimulating system has at least one light source, wherein the optogenetic systems of the engineered cells are configured to receive a light generated from the at least one light source such that the generated light operably controls said production of the at least one type of therapeutic agent (Par. 15, 51, 55, 79) wherein the engineered cells start said production of the at least one type of therapeutic agent when the optogenetic systems of the engineered cells receive the generated light having the first wavelength from the optical stimulating system (Par. 15, 51, 55, 79); and
A controller (140) in communication with the optical stimulating system and a sensing system (e.g. 130 – but consider also configurations with additional sensors 660), wherein the controller is configured to control the production of the at least one type of therapeutic agent according to a control algorithm (Par. 6, 7, 53, 54, 70, 82, 83) provided on a memory unit (see generally 650, Par. 97) which calculates, based on sensor information, a current production rate of the therapeutic agent and dynamically adjusts one or more parameters of the optical stimulating system to control the production of the therapeutic agent (Par. 6, 7, 54, 70).
Park, as modified, discloses the invention substantially as claimed except that that the system is configured such that the engineered cells stop production of the therapeutic agent in response to a second light having a second wavelength, the optogenetic system being configured to generate the light having the second wavelength from the optical stimulating system. While Park does contemplate that the system may generate a plurality of different wavelengths of light to different effect (see e.g. Par. 73), Park does not explicitly contemplate using a second wavelength of light to explicitly stop production of the therapeutic agent. However, Muller discloses that in the field of genetically engineered, optogenetically responsive cells it is known to engineer the cells such that they can have production of a therapeutic agent selectively turned on and off, wherein a first wavelength of light activates the cells to produce the agent of interest and exposure of the cells to a second, different wavelength of light deactivates the cells to stop production of the therapeutic agent immediately (Abstract; Box 3, Protocol). It would have been obvious for one having ordinary skill in the art at the time the invention was made to configure the cells and system of Park to immediately cease production of the therapeutic agent when exposed to a second wavelength of light produced by the optical stimulating system, as disclosed by Muller, in order to more accurately provide release of the therapeutic agent by using the second wavelength to immediately cease production of the agent ensuring no additional agent is produced by the cells during a ramp-down period associated with ceasing exposure of the cells to the first wavelength of light.
Park discloses the invention substantially as claimed except that optogenetically engineered cells also release a “reporter agent”. In the instant case, lacking any reference to the utility of the “reporter agent” it is submitted that such a “reporter agent” could logically be considered to comprise any molecule other than the specific therapeutic agent of interest. For example, Park discloses that in some instances the cells may be stimulated to secrete insulin (Par. 52 – among other drugs), but also suggests that the cells could ALSO be stimulated to secrete glucagon (Par. 73). In such instances it is submitted that insulin could be considered the “therapeutic agent” and glucagon could be considered a “reporter agent”. However, other molecules understood to be released during production of the therapeutic agent of interest, e.g. inactive waste products and analytes (e.g. C-terminus basic amino acids) indicative of insulin synthesis and activation.
However, should Examiner’s arguments not be found persuasive the following is presented. McFarland discloses a related bioreactor device (Fig. 1A) wherein along with the molecule/therapeutic agent of interest the cells may be configured to produce a “detectable label” (e.g. a reporter agent) along with therapeutic in order to allow detection of the target molecule more easily by the sensor arrangement to determine the levels of produced therapeutic agent (Par. 117). It would have been obvious for one having ordinary skill in the art at the time the invention was made to configure the cells of Park to product a detectable, reporter agent along with the therapeutic agent, as disclosed by McFarland, in order to permit a secondary method by which production of the therapeutic can be confirmed and quantified, thereby helping to assist with accurate and effective dosing allowing the device to start and stop agent synthesis dependent upon confirmation (see also Park, Par. 54 with photosensor determination of agent production supplemented by any of the various detectable labels suggested by McFarland inclusive to biochemical signals and fluoro-tags).
In the instant case McFarland fails to explicitly suggest that the ratio of reporter/labels to the therapeutic is produced specifically at a “fixed ratio”. Although given that the production of the labels along with the production of the agent is incident to the degree of light exposure it follows that the ratio will be fixed based on the specific chemical pathways of the cell incident to the light exposure. However, Berniac discloses that such labels/tags can be made at “a fixed molar ratio (e.g. a 1:1 ratio by end labeling) to allow the number of tether molecules to be determined” (Par. 99). It would have been obvious for one having ordinary skill in the art at the time the invention was made to configure the system of modified Park to produce the agent and label/reporter at a fixed ratio, as disclosed by Berniac, so that the reporter/label/tag can be used to accurately correlate and measure the exact payload/therapeutic agent produced by the sensor system.
Park discloses the invention substantially as claimed except that device further comprises a “media cartridge” in fluid communication with the cell cartridge providing cell media to the cell cartridge. Rather Park (and Aebischer) suggests that endogenous bodily fluids could supply the cells with the necessary media for their metabolism (Par. 61. However, as discussed above, McFarland discloses a similar bioreactor for using bioengineered cells to produce various agents (Abstract). McFarland discloses that the device may have a media module/cartridge (178) integrated therewith (Par. 516) which can supply the cell source/cartridge with necessary cell media (180) to permit their cell metabolism and production of the agent of interest (Par. 93, 159, 244, 614), the device comprising a pump (160 – Par. 519, 384) in fluid communication with the media cartridge and the cell cartridge, wherein the pump is configured to pump the cell media from the media cartridge into the cell cartridge. It would have been obvious for one having ordinary skill in the art at the time the invention was made to configure the system of modified Park to include a media cartridge and pump, as disclosed by McFarland, in order to provide the cells with any additional nutrients, reagents…etc. that they might need for optimal cell maintenance and product of the therapeutic agent thereby supplanting the need to utilize endogenous bodily fluids for cell metabolism.
Park discloses the invention substantially as claimed except that that the device comprises a “cannula” for affecting delivery. Park does not explicitly discuss how the agent is secreted into the blood stream. However, as discussed above, Aebischer discloses a similar bioreactor (20) which likewise uses engineered cells to produce therapeutic agents. Aebischer discloses the device to comprise a cannula (re: catheter 22) having a first cannula end in fluid communication with the cell cartridge (see Fig. 2) and a second cannula end configured to be in fluid communication with the subject (see Fig. 1). It would have been obvious for one having ordinary skill in the art at the time the invention was made to utilize a catheter/cannula to convey the agent between the cell cartridge and the subject in the device of Park, as disclosed by Aebischer, in order to utilize a known component which has been appreciated by the prior art for such a utility thereby solving the generic disclosure of Park via a known, predictable solution to obtain only an expected outcome via a system with which the ordinary artisan would be reasonably familiar.
Regarding Claims 2 and 24, Park discloses a filter (re: “selective membrane”) disposed between the cell cartridge and the agent outlet (re: the second end of the cannula as modified in view of Aebischer), wherein the filter is configured to selectively permit the at least one type of therapeutic agent passing through the filter and entering into the subject's body through the second end of the cannula (Par. 16, 51, 61).
Regarding Claims 3 and 28, Park discloses a battery (550) configured to provide power supply to the device. While such a power source is only explicitly discussed with respect to the embodiment 500, Examiner submits that inclusion of such a power supply to power the electronic components of the other embodiments of Park is both obvious and expected (see Par. 94).
Regarding Claim 5, the sensing system of Park (130), as modified in view of McFarland, is configured to detect a fluorescent signal or bioluminescence signal generated by the reporter agent (see McFarland – Par. 117, e.g. “fluorescent molecules such as fluorophores”), wherein the engineered cells stop the production of the at least one type of therapeutic agent when the sensing system detects a predetermined level of the fluorescent signal or bioluminescence signal generated by the reporter agent (see Park, Par. 53-54, 82, 83 – with consideration as to modifications by McFarland and Berniac to measure the expression of the label/tag molecule produced in a fixed ratio in association with the therapeutic agent to determine the volume of therapeutic agent produced).
Regarding Claims 8 and 30, Park discloses the invention substantially as claimed except that the media cartridge is refillable. However, Park does suggest refilling of the drug cartridge (Par. 85). As such, it would have been obvious for one having ordinary skill in the art at the time the invention was made to also permit refilling of the media cartridge of modified Park, as discussed in association with the cell cartridge, in order to ensure that the cells are provided with a sufficient source of media to permit agent production.
Regarding Claims 9 and 25, Park, as modified (see McFarland as applied above), provides for the pump to create a pressure necessary for the at least one type of therapeutic agent passing through the filter and entering into the subject's body through the second end of the cannula.
Regarding Claims 10 and 32, Park, as modified, discloses the invention substantially as claimed except that the device further comprises an intake cannula in fluid communication with the subject and is configured to receive body fluid from the subject. Park does suggest that bodily fluids can be conveyed to the system, but does not particularly disclose a specific means to do so. However, Aebischer discloses that such systems may be configured with a portal (104) for permitting the introduction of bodily fluids into the system, wherein pumps can be used to affect the drawing of such fluids into the system. While Aebischer does not explicitly recite a cannula associated with that particular inlet, Examiner submits that it would have been obvious to utilize an additional catheter/cannula (see e.g. 22), particularly in instances where the system is provided extracorporeally. It would have been obvious for one having ordinary skill in the art at the time the invention was made to configure the device of Park to include an inlet cannula/catheter, in order to permit the drawing of various bodily fluids into the device for purposes of analyte sensing, distribution of nutrients, etc.
Regarding Claims 11 and 33, Park, as modified by Aebischer, discloses the intake cannula is in fluid communication with the cell cartridge, wherein in use, the received body fluid enters into the cell cartridge, wherein the cell cartridge is configured to collect, expand, and prime cells in the body fluid of the subject (see generally Fig. 2 and 5 – Aebischer).
Claim(s) 7, 12, 29, and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 2022/0047810 (“Park”) in view of in view of U.S. Patent No. 5,011,472 (“Aebischer”), “Control of Gene Expression Using a Red- and Far-Red Light-Responsive Bi-Stable Toggle Switch” (“Muller”), U.S. Publication No. 2022/0325240 (“McFarland”), and U.S. Publication No. 2014/0186850 (“Berniac”) as applied above, and further in view of U.S. Publication No. 2019/0090801 (“Rogers”).
Regarding Claims 7 and 29, Park, as modified, discloses the invention substantially as claimed except that the media cartridge is replaceable and detachable (as opposed to merely refillable). However, McFarland discloses “in various embodiments, cartridges can be replaced…” (Par. 115). Furthermore, Rogers discloses a similar optogenetic bioreactor where “replaceable fluid-containing cartridges (analogous to ink jet printer cartridges) might represent an attractive future design feature. As such, it would have been obvious for one having ordinary skill in the art at the time the invention was made to configure the media cartridge of Park to be detachable and replaceable, as disclosed by Rogers, in order to ensure that a sufficient supply of cell media is provided at all times. It has been held that constructing a device of a plurality of separable and replaceable parts is obvious and predictable, see In re Dulberg, 289 F.2d 522, 523, 129 USPQ 348, 349 (CCPA 1961).
Regarding Claims 12 and 31, Park suggests that the cell cartridge may be replaceable (Par. 10, 17), although this recitation might only suggest refilling of the drug reservoir when it recites “replace” (see Par. 22 and 85). However, McFarland discloses “in various embodiments, cartridges can be replaced…” (Par. 115). Furthermore, Rogers discloses a similar optogenetic bioreactor where “replaceable fluid-containing cartridges (analogous to ink jet printer cartridges) might represent an attractive future design feature. As such, it would have been obvious for one having ordinary skill in the art at the time the invention was made to configure the cell cartridge of Park to be detachable and replaceable, as disclosed by Rogers, in order to ensure that a sufficient supply of cell media is provided at all times. It has been held that constructing a device of a plurality of separable and replaceable parts is obvious and predictable, see In re Dulberg, 289 F.2d 522, 523, 129 USPQ 348, 349 (CCPA 1961).
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 2022/0047810 (“Park”) in view of in view of U.S. Patent No. 5,011,472 (“Aebischer”), “Control of Gene Expression Using a Red- and Far-Red Light-Responsive Bi-Stable Toggle Switch” (“Muller”), U.S. Publication No. 2022/0325240 (“McFarland”), and U.S. Publication No. 2014/0186850 (“Berniac”) as applied above, and further in view of U.S. Publication No. 2009/0311133 (“Pang”).
Regarding Claim 19, Park, as modified, discloses the invention substantially as claimed except that the sensing system comprises a photodiode. While both Park and McFarland disclose that photosensors can be used to detect reporter agents/detectable tags, use of a “photodiode” is never explicitly suggested. However, Pang discloses that such photosensing arrangements can be affected by a photodiode (Par. 151). It would have been obvious for one having ordinary skill in the art at the time the invention was made to utilize a photodiode, as disclosed by Pang, as the photosensor of modified Park, in order to sense the presence of various detectable tags (see e.g. McFarland), and permit control of therapeutic generation response to the sensed agent/tag (see Park), in order to utilize a known, specific species of solution in replace of a generic recitation to obtain a known, predictable, and expected outcome.
Response to Arguments
Applicant's arguments filed with respect to the claims have been fully considered but they are not persuasive or are moot in view of the new ground(s) of rejection.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant's argument that Aebishcer fails to provide sufficient direction as to the modification of Park to be wearable versus implantable, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Furthermore, Examiner submits that “wearable” is only recited in the preamble of the instant claims and not provided in association with any specific physical structure or hardware found in the body of the claims. When reading the preamble in the context of the entire claim, the recitation of “wearable” is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02.
Additionally, it is submitted that the implantable may reasonably be considered a sub-species of “wearable”, wherein an implantable device is effectively worn internally of the body, the phrase “wear” being defined as “to bear or to have on the person” or “to carry on the person”, see Merriam-Webster’s Online Dictionary. But even presuming that wearable is interpreted to relate to ONLY extracorporeal constructions, Examiner submits that such a broad limitation is obvious in light of the prior art, whereby there presents a clear and distinct benefit to perform any of the necessary product redesign and configurations as an extracorporeal device would eliminate the need for an expensive and invasive surgical procedure to implant the device, would allow the device to be more easily replaced or serviced without surgical revision, would allow the device to be made using different materials and different engineering standards simplifying construction and reducing costs, would allow the device to be larger…etc. Any of these benefits which would be immediately appreciated by the ordinary artisan without express suggestion, directly by the prior art constitutes a sufficient motivation to consider modification of the device of Park to be wearable.
Conclusion
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 WILLIAM R CARPENTER whose telephone number is (571)270-3637. The examiner can normally be reached Mon. to Thus. - 7:00AM to 5:00PM (EST/EDT).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, KEVIN SIRMONS can be reached at (571) 272-4965. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM R CARPENTER/Primary Examiner, Art Unit 3783 10/07/2026
