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 .
Applicant’s arguments and amendments have been thoroughly reviewed and considered. Claims 19, 21, 27, 29, and 32 have been canceled. Claims 18, 20, 22-26, 28, 30-31, and 33-37 are pending and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement filed 5/16/2023 was previously noted in the Non-Final Office Action to not have provided copies of non-patent literature documents 8 and 9 (the International Search Report and Written Opinion for PCT/KR2021/015826). Copies of these documents were submitted in the file wrapper on 5/16/2023, and so these references have now been considered. A newly annotated copy of the Information Disclosure Statement submitted 5/16/2023 with all references fully considered has been provided.
Response to Applicant’s Amendments
Drawings
The drawings were objected to because Figures 8c-e were not legible. In light of Applicant’s amended drawings submitted 3/18/2026, these objections have been withdrawn.
Claim Objections
Claims 18, 24, 31, and 34-35 were objected to due to minor informalities. In light of Applicant’s amendments to the claims submitted 3/18/2026, these objections have been withdrawn.
35 USC 112(b) Rejections
Claims 20-21, 24, 28-29, and 33 were rejected for various indefiniteness issues. In light of Applicant’s amendments to the claims submitted 3/18/2026, these rejections have been withdrawn for all currently pending claims. Claims 21 and 29 have been canceled, and so these rejections have been rendered moot.
35 USC 103 Rejections
Claims 18-37 were rejected as being nonpatentable over Jiang et al. (Analytical Methods, 2014; cited in Applicant’s IDS) in view of Jakobsen et al. (Organic & Biomolecular Chemistry, 2016; cited in Applicant’s IDS).
In light of Applicant’s amendments to the claims submitted 3/18/2026, these rejections have been withdrawn for all currently pending claims. Claims 19, 21, 27, 29, and 32 have been canceled, and so these rejections have been rendered moot. See also “Response to Applicant’s Arguments” and new grounds of rejection below.
Double Patenting Rejections
Claims 18-19, 21-24, 27, 29-32, 34-35, and 37 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-21, 23, 25, 28-29, 31, 33, and 37 of copending Application No. 18/278,584 (reference application).
The terminal disclaimer filed on 3/18/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of the full statutory term of any patent granted on pending reference application 18/278,584 has been reviewed and is accepted. The terminal disclaimer has been recorded.
The terminal disclaimer is also accompanied by a complete reply to the previous Non-Final Office Action. Thus, these rejections have been withdrawn for all currently pending claims. Claims 19, 21, 27, 29, and 32 have been canceled, and so these rejections have been rendered moot.
Response to Applicant’s Arguments
Regarding the 35 USC 103 Rejections presented in the Non-Final Rejection, Applicant first summarizes the differences between each of Jiang and Jakobsen in relation to the instant invention (see the table in the Remarks, pages 15-16). Applicant then states that the present application’s configuration for the hydrogel with the first and second probes within liposomes “prevents premature interaction between probes and suppresses interference noise that would otherwise arise from unintended probe-probe reactions in solution,” (Remarks, page 16).
Applicant states that Jiang “teaches away” from the claimed invention because said reference does not teach does not teach that probes are separated on different liposomes (Remarks, page 17). As Jakobsen does not disclose the use of liposomes with signal generation due to hairpin opening and fluorescence quenching mechanisms, Applicant argues that the liposomes of Jakobsen cannot act as a substrate for the probes of Jiang as this “oversimplifies the technical realities of CHA systems,” and neither reference provides evidence that CHA systems could operate under separate liposome conditions. Jakobsen’s liposomes also act as a detection signal, and the reference does not suggest “decoupling liposome-liposome interaction from signal generation, as required by the claims,” (Remarks, page 18). Applicant also states that the provided motivation is not sufficient to abandon the method of Jiang to include liposome components, and that the references do not provide a reasonable expectation of success (Remarks, page 18).
Regarding the assertion that Jiang “teaches away” from the claimed invention, this is not an accurate use of the phrase. MPEP 2145 X (D) 1 states, “‘the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….’ In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). See also UCB, Inc. v. Actavis Labs, UT, Inc., 65 F.4th 679, 692, 2023 USPQ2d 448 (Fed. Cir. 2023) ("a reference does not teach away if it merely expresses a general preference for an alternative invention but does not criticize, discredit or otherwise discourage investigation into the invention claimed.") (internal quotations omitted) (quoting DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed. Cir. 2009)); and Schwendimann v. Neenah, Inc., 82 F.4th 1371, 1381, 2023 USPQ2d 1173 (Fed. Cir. 2023).” Jiang does not discuss the use of liposomes, and so does not discourage or disparage such use. The fact that the reference teaches the use of catalyzed hairpin assembly without liposomes alone does not provide evidence that the reference teaches away from the use of such liposomes.
Applicant’s discussion of the implications of the claimed invention extends beyond the scope of the currently claimed invention. Claims 18, 20, 22-26, 28, and 34-37 are product claims, and do not have any requirements for how they must be used. Though reporters and quenchers are present and the probes may be recited as hairpins, there is no particular fluorescence detection recited. Claims 30-31 and 33 are method claims, but all they require is using the composition of claim 18 with a sample and surfactant, with no particular detection methods described. Therefore, the detection applications described by Applicant in their Remarks (see pages 12-13, section (1), the table of pages 15-16, and page 18, paras. 2-3) are not currently applicable to every embodiment of the claimed invention, regardless of the benefits of particular embodiments of the invention described by the instant specification (see MPEP 2111.01 II, which notes that it is improper to import claim limitations from the specification).
In claims 18, 30, and 34, the first and second probes must be “supported on a first/second liposome.” In claim 23, the first and second probes are “supported” by the first and second liposomes. There is no requirement that the probes must be inside the liposomes, as Applicant argues in the table on pages 15-16 of their Remarks. For example, the probes may be attached to the outside of the liposomes, as shown in the probes/liposomes of Jakobsen. There is also no claimed requirement that the probes must be so far away from one another that they are spatially separated and cannot react with one another “prematurely.” Additionally, no liposome degradation is explicitly required by the claims, nor is the actual binding of a probe to a target nucleic acid. Though the spatial separation described by Applicant’s Remarks (see section B on page 16) may be achieved in some embodiments of the instant invention, these are not currently explicitly claimed. The statement of such benefits in some embodiments provided by the specification is not sufficient to read such benefits/embodiments alone into the instant claims (see MPEP 2111.01 II, which states that it is improper to import claim limitations from the specification).
Regarding the combination of Jiang in view of Jakobsen, Jiang teaches CHA methods with probes that have the claimed structure of the first and second probes. It is noted that the newly amended claims all require that the second probe also have a hairpin, and Jiang was already used to teach such structure in the Non-Final Rejection (see para. 24). Jakobsen is then used to teach methods of probe attachment to liposomes, where said probes are on the outside of the liposomes and are capable of attachment to both each other and a target sequence (something the probes of Jiang are also capable of), and where each probe used may be different (see para. 26 of the Non-Final Rejection).
In the combination of these references (para. 27), it is stated that liposomes can be used to attach to the probes of Jiang. Jakobsen teaches that their method is useful for diagnostic assays, and provides benefits over other types of such assays. Jiang also teaches that their probes can be used for detecting targets in biological samples, thus providing relevance to diagnostics as well (see para. 27 of the Non-Final Rejection). The ordinary artisan would be capable of utilizing ordinary knowledge, skill, and creativity in the art to realize the benefits of performing diagnostic assays (e.g. more accurate pathogen/mutation detection and potentially earlier diagnosis to improve disease prognoses; see MPEP 2141.03 I). Though the detection methods of Jakobsen alone do involve absorbance measurements (see Figure 3 for example), as the probes of Jiang contain fluorophores and quenchers, these absorbance detection methods would not be needed. As Jakobsen also notes that probe anchors to liposomes can be placed anywhere on the probe sequence, they can be placed so as to not interfere with the probe activity of the probes of Jiang.
Such a combination of references in the context of obviousness rejections is described in MPEP 2143 I (A), which states, “The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art.” The functions of the probes and liposomes would not be altered, as the probes would still be capable of functioning as in Jiang and the liposomes would still be capable of holding probes and being used in target detection assays as is shown in Jakobsen, and the results of the combination would thus be predictable.
Furthermore, MPEP 2143.01 V states, “Although statements limiting the function or capability of a prior art device require fair consideration, simplicity of the prior art is rarely a characteristic that weighs against obviousness of a more complicated device with added function." In re Dance, 160 F.3d 1339, 1344, 48 USPQ2d 1635, 1638 (Fed. Cir. 1998) (Court held that claimed catheter for removing obstruction in blood vessels would have been obvious in view of a first reference which taught all of the claimed elements except for a "means for recovering fluid and debris" in combination with a second reference describing a catheter including that means. The court agreed that the first reference, which stressed simplicity of structure and taught emulsification of the debris, did not teach away from the addition of a channel for the recovery of the debris.). Similarly, in Allied Erecting v. Genesis Attachments, 825 F.3d 1373, 1381, 119 USPQ2d 1132, 1138 (Fed. Cir. 2016), the court stated "[a]lthough modification of the movable blades may impede the quick change functionality disclosed by Caterpillar, ‘[a] given course of action often has simultaneous advantages and disadvantages, and this does not necessarily obviate motivation to combine’" (quoting Medichem, S.A. v. Rolabo, S.L., 437 F.3d 1157, 1165, 77 USPQ2d 1865, 1870 (Fed. Cir. 2006).” Thus, while the solution-based probes of Jiang may be simpler than the combination of Jiang in view of Jakobsen, this does not obviate the obviousness to combine these two references. The addition of the liposomes in Jiang in view of Jakobsen would also provide its own advantages – as probes attached to liposomes may be easily gathered and manipulated by manipulating the liposome, without also manipulating non-probe or non-target nucleic acids that may also be present in a sample or solution.
Regarding Applicant’s point in the context of discussing reasonable expectation of success that “this does not address whether the catalyzed hairpin assembly mechanism of Jiang, whose signal amplification depends on rapid, repeated probe interactions in solution, would remain operative when the probes are immobilized on separate liposomes,” this signal amplification is based on free target nucleic acid in solution being capable of generating a fluorescent signal in the probes based on hybridization patterns. Such amplification is taken at a single point after incubation, and so once the fluorescent signal is generated due to the hybridization of two probes, that signal generally remains unless further manipulation of the reaction occurs (see Jiang Figure 1 and pages 9478-9479, “Standard procedures of the CHA-based miRNA assay” and “Principle of the CHA-based MiRNA assay”). Thus, as the hybridization of the probes is not impacted by combining Jiang in view of Jakobsen, the signal generation of the probes would also not be affected, particularly in light of the flexible probe anchoring of Jakobsen. As this is fluorescence detection, this can easily be distinguished from liposome-liposome interactions, which do not rely on fluorescence. The combination of Jiang in view of Jakobsen presented in the Non-Final Rejection does not suggest that the detection of Jakobsen be utilized.
Finally, as to Applicant’s argument that neither Jiang nor Jakobsen provide evidence that CHA could operate under separate liposome conditions, it is noted that for an obviousness rejection, no conclusive proof of efficacy is required, nor is an absolute predictability of success (see MPEP 2143.02 I-II). While combining the teachings of Jiang in view of Jakobsen in the manner described in the Non-Final Rejection may require optimization, such optimization is possible for one of ordinary skill in the art – as exemplified by Jiang, whose teachings additionally show that CHA methods are viable under a variety of buffer concentrations, temperatures, probe ratios, target types and concentrations, and fluorescence wavelengths (Figures 2-7). These data provide evidence that the CHA method of Jiang is robust, and that there would be a reasonable expectation of success in modifying it.
It is noted that all claims now require the use of a hydrogel in which the liposomes are disposed. A hydrogel was initially taught in the Non-Final Rejection by Gaillard. Applicant does not specifically point out supposed deficiencies in the rejection of Jiang, in view of Jakobsen, and in view of Gaillard, nor do Applicant’s Remarks discuss Gaillard in detail.
Thus, Applicant’s arguments are not considered persuasive to obviate the use of the previously cited references in the context of obviousness rejections. In light of Applicant’s amendments to the claims, new grounds of rejection are required, but the relevant portions of the rejections presented in the Non-Final Rejection are reiterated below.
Claim Interpretation
Regarding claims 18 and 34, both the first and second probe must be “configured to hybridize with the target nucleic acid.” However, as these claims are product claims, no specific method is required that mandates such hybridization occur for each probe. Thus, these limitations will be considered to be met if prior art teaches two probes that contain regions that are capable of hybridizing to a target nucleic acid, even if said hybridization is not taught by said prior art.
Regarding claim 36, it is noted that “a house-keeping gene sensing part” is not specifically defined in the instant specification. Though this part is noted in the claim to be “for detecting a house-keeping gene,” there does not appear to be any particular structure of the part that limits or specifies its use for specifically detecting a house-keeping gene. Therefore, any sensor which contains a part that would be capable of detecting a house-keeping gene, even if it is not described as specifically for detecting a house-keeping gene, will be considered to meet this claim limitation.
Claim Rejections - 35 USC § 112(a)
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 18, 20, 22, 30-31, and 33-37 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 18 and 34 recite that the second probe is “configured to hybridize with the target nucleic acid.” As stated in the “Claim Interpretation” section above, this indicates that the second probe is capable of hybridizing to the target nucleic acid, even if such hybridization does not actually occur. However, such a feature of the second probe is not recited in the instant specification, and in Figure 1, Probe B (analogous to the second probe as claimed) contains regions a*, b*, and c. The target nucleic acid contains b*, which is the same as a portion of Probe B. Probe B itself does not appear to contain a region that can hybridize to the target nucleic acid, and no such hybridization is shown in the figure. This is corroborated by para. 52 of the instant specification, which states that the second probe may comprise the target sequence.
Thus, the disclosure of a second probe that is “configured to hybridize with the target nucleic acid” Is considered new matter. Claims 20, 22, 30-31, 33, and 35-37 are rejected due to their dependence on rejected claims 18 and 34.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 22, 31, and 35 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 22 depends on claim 18 and states that a “hydrogel composition” is required. However, claim 18 has been amended to state that a hydrogel is provided in the composition. As claim 22 does not describe any additional structure or function of the hydrogel of claim 18, claim 22 is considered to fail to further limit the subject matter of the claim upon which it depends.
Claim 31 depends on claims 18 and 30 and states that the liposomes that support the first and second probes are simultaneously contained within a hydrogel. Claim 30 recites a method that utilizes the composition of claim 18, and claim 18 requires that the first and second liposomes are already both contained within the hydrogel. Thus, claim 31 is considered to fail to further limit the subject matter of the claims upon which it depends.
Claim 35 depends on claim 34 and states that the composition of the claim is in the form of a hydrogel in the sensing part of the sensor. However, claim 34 already states that the composition is in the sensing part and that the composition contains a hydrogel where the liposomes are situated. Thus, claim 35 is considered to fail to further limit the subject matter of the claims upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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.
Claims 18, 20, 22-24, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al. (Analytical Methods, 2014; cited in Applicant’s IDS), in view of Jakobsen et al. (Organic & Biomolecular Chemistry, 2016; cited in Applicant’s IDS), and in view of Gaillard et al. (US 2019/0307691 A1).
Jiang teaches a fluorescence assay for detecting miRNA involving catalyzed hairpin assembly. In this assay, two hairpin probes are used, one of which has a fluorophore/quencher pair that is quenched when the stem of the hairpin is in place, and the other which does not have a fluorophore or quencher (Abstract). The two hairpins also have sequences that are complementary to each other (page 9478, column 1, para. 1). The hairpin with the fluorophore/quencher (hereafter called the first probe) contains a sequence that is complementary to a target (see 1, 2, 3, of P1 in Figure 1, that is complementary to 1*, 2* and 3* of an miRNA), as well as a portion that is not complementary to the target (see 4* of P1). The hairpin without the fluorophore/quencher (hereafter called the second probe) contains a portion that is complementary to the target sequence (see 3 of P2), a sequence that is complementary to the off-target sequence of the first probe (see 4 of P2), and a sequence that is complementary to the on-target portion of the first probe (see 2* and 3*; instant claim 20). The first probe contains a FAM reporter and a black hole quencher (BHQ; see Figure 1 caption).
However, Jiang does not teach that each probe is supported on a separate liposome, nor the use of hydrogels.
Jakobsen teaches methods of probe attachment to liposomes (Abstract). These probes are intended to detect disease related genetic markers (page 6985, column 1, para. 1), and are attached to liposomes through anchors that that can be attached anywhere in a nucleotide sequence (page 6986, column 2, para. 2). Though the probes taught by Jakobsen are DNA probes (see Table 1), RNA targets can still be detected (page 6988, columns 1-2 joining para.). Jakobsen shows probe designs where it is possible for probes to hybridize to one another and to a target sequence, where differently designed probes are present on different liposomes (Figure 8). Jakobsen teaches that this method is simple, is not sensitive to the presence of sequences related to the target, and can be used with biological samples. The probes can also easily be attached without the use of long-linkers, and the method is low-cost (page 6993, “Conclusion).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to combine the teachings of Jiang and Jakobsen to arrive at the probe and liposome combination of instant claim 18. Jiang tests their probes in vitro with serial dilutions of an miRNA target (page 9478, column 2, para. 1), but by utilizing the liposomes of Jakobsen, these probes could be incorporated into a simple, low-cost, effective detection assay that can detect targets in biological samples, thus making the probes of Jiang relevant to diagnostic assays. Jiang notes that their probes may prove useful for clinical diagnosis (page 9481, column 2, para. 1), so by incorporating them into a method such as Jakobsen’s that performs such diagnoses, the research presented by Jiang would be advanced. Jakobsen utilizes liposomes as an alternative to traditional gold nanoparticles for molecular diagnostics, as attachment of probes to liposomes allows for more strong attachments while maintaining full lateral probe mobility (page 6985, column 2, para. 1). These reasons would motivate the ordinary artisan to combine these references. There would be a reasonable expectation of success as Jakobsen teaches that probes anchors can be placed anywhere on the probe sequences (so they can be designed so as to not interfere with intended probe hybridization), shows that differently designed probes would be separated on different liposomes, and shows hybridization of probes to one another and a target, providing evidence that the function of the probes of Jiang could be maintained.
However, neither reference teaches that the liposomes can be situated in a hydrogel.
Gaillard teaches compositions for releasing molecules through hydrogels containing liposomes (Abstract). The reference teaches that hydrogels can be used for diagnostic purposes, where liposomes entrapped in hydrogels can contain fluorescently labeled probes. These hydrogels can be used in vivo by being injected into a subject (para. 216).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Gaillard to attach the liposome composition of Jiang in view of Jakobsen to a hydrogel to arrive at the invention of claims 18 and 22. Gaillard teaches that hydrogels containing a composition with probes and liposomes can be used for diagnostic purposes, which is in line with the goals of Jiang and Jakobsen described above. Gaillard teaches that these methods can be minimally-invasive for a subject, and this allows for an in vivo diagnostic method, which may be more accurate or relevant to a patient than in vitro methods, such as those of Jiang in view of Jakobsen. This would be motivating to the ordinary artisan. There would be a reasonable expectation of success as Gaillard is mainly directed to the use of hydrogels with liposomes, and teaches their combination with fluorescent probes, which would encompass those of Jiang in view of Jakobsen.
Thus, claims 18, 20, and 22 are prima facie obvious over Jiang, in view of Jakobsen, and in view of Gaillard.
Instant claims 23 and 28 require the same limitations as instant claims 18 and 20 respectively, with the exception that the second probe of claims 23 and 28 need not be configured to hybridize to the target nucleic acid. However, such a configuration is not prohibited by said claims. Thus, Jiang, in view of Jakobsen, and in view of Gaillard would read on these claims for the same reasons described above for claims 18 and 20.
Regarding claim 24, Gaillard teaches examples where the hydrogel is made of a polyacrylic acid mixture or polyacrylamides (paras. 158 and 217), a hyaluronic acid mixture (para. 158), polylactic acid (para. 217), soluble celluloses (para, 218), and poly(ε-caprolactone) (para. 218). As the hydrogel of Gaillard is used in the combination of Jiang, in view of Jakobsen, and in view of Gaillard, it would be prima facie obvious to have this hydrogel be made of materials also taught by Gaillard.
Claims 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al. (Analytical Methods, 2014), in view of Jakobsen et al. (Organic & Biomolecular Chemistry, 2016), in view of Gaillard et al. (US 2019/0307691 A1), and further in view of Rotem et al. (US 2019/0125937 A1).
Jiang, in view of Jakobsen, and in view of Gaillard teaches the inventions of claims 18, 20, 22-24, and 28, as described above. And though Gaillard teaches materials for the hydrogel, they do not teach that the hydrogel is photocured or a mixture of polyethylene glycol (PEG) and polyethylene glycol diacrylate (PEG-DA).
Rotem teaches creating composite membranes via the use of polyethers and a photoinitiator (Abstract). A matrix made of hydrogels can be created, where the hydrogel can be a combination of PEG and PEG-DA (para. 70). Rotem notes that liposomes can be incorporated into the hydrogel (para. 85). The membrane can be photocured with the photoinitiator via exposure to UV light (para. 7), and Rotem specifically teaches performing this utilizing PEG-DA (para. 114). The reference teaches that their membranes can have medical uses, such as implantation into a subject (paras. 2 and 12).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the hydrogel of Rotem in the method of Jiang, in view of Jakobsen, and in view of Gaillard. This would amount to simple substitution of the hydrogel material and method of creation. MPEP 2143 I (B) states, “The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art.” Making hydrogels with PEG and PEG-DA and utilizing photocuring were known in the art, as evidenced by Rotem, and this substitution would yield predictable results, as the hydrogel would still be able to include liposomes and be capable for use within a subject, as in the case of Jiang, in view of Jakobsen, and in view of Gaillard, as these aspects are also taught by Rotem.
Thus, claims 25-26 are prima facie obvious over Jiang, in view of Jakobsen, in view of Gaillard, and further in view of Rotem.
Claims 30, 31, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al. (Analytical Methods, 2014), in view of Jakobsen et al. (Organic & Biomolecular Chemistry, 2016), in view of Gaillard et al. (US 2019/0307691 A1), and further in view of Lopez et al. (Langmuir, 2018).
Jiang, in view of Jakobsen, and in view of Gaillard teaches the inventions of claims 18, 20, 22-24, and 28, as described above. However, none of these references teach the use of a surfactant.
Lopez teaches general design and use for liposomes linked to DNA (Abstract). Figure 2C shows that the addition of a surfactant such as Triton X-100 can rupture a liposome, releasing contents. Figure 10B shows such a surfactant treatment when DNA is attached to a liposome surface, and Lopez teaches that this can release fluorescent cargo (page 15008, column 2, para. 3). Additionally, Lopez teaches that DNA aptamers can bind to cells, such as cancer cells (page 15002, column 2, para. 1), and that DNA conjugated to a liposome can be delivered into cancer cells (page 15003, column 1, para. 1 and page 15008, column 1, para. 4). This method in particular can be used for drug delivery where drug molecules can be stored within the liposome (page 15008, column 1, para. 3).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Lopez with the hydrogel-liposome composition of Jiang, in view of Jakobsen, and in view of Gaillard to develop a method for target detection and drug delivery using liposomes by adding a sample, such as cancer cells, and a surfactant to said liposome composition. By combining these methods, it would allow for diagnosis and treatment of a sample, which would be beneficial in that it could provide information on if a patient’s particular condition is associated with a target biomarker, and if said condition is responsive to a particular treatment. This could be done in a minimally invasive way utilizing tumor biopsy tissue already taken from a patient, preventing the need for taking additional samples. By obtaining treatment efficacy information for a patient before treatment begins, this could save time and resources that may otherwise be spent on treatments a patient is not responsive to, which would be motivating to the ordinary artisan. There would be a reasonable expectation of success as cancer samples and surfactants are well-known in the art, as evidenced by Lopez, and this reference cites several studies that successfully utilized liposomes for specific targeting and drug delivery with cancer cells (page 15008, “Drug Delivery”). Furthermore, the hydrogel itself is injectable (see para. 216 of Gaillard), and so could easily be injected onto a sample. The hydrogel would also provide additional stability for the liposome composition, so that a majority of degradation/lysis would only occur upon exposure to the surfactant. This injection capability could then be utilized upon finding an effective treatment for a patient, as said treatment could be injected into a patient via the hydrogel liposome composition. There would be a reasonable expectation of success because, as described above, Gaillard teaches a hydrogel containing probes and liposomes, and the addition of the hydrogel would not affect the use of the sample or the surfactant in the method of Jiang, in view of Jakobsen, in view of Gaillard, and further in view of Lopez.
Thus, claims 30-31 are prima facie obvious over Jiang, in view of Jakobsen, in view of Gaillard, and further in view of Lopez.
Instant claim 33 requires the same limitations as instant claim 20 within the method of instant claim 30. Thus, Jiang, in view of Jakobsen, in view of Gaillard, and further in view of Lopez would read on this claim for the same reasons as described above.
Claims 34-37 are rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al. (Analytical Methods, 2014), in view of Jakobsen et al. (Organic & Biomolecular Chemistry, 2016), in view of Gaillard et al. (US 2019/0307691 A1), and further in view of Craighead et al. (US 2012/0028811 A1).
Jiang, in view of Jakobsen, and in view of Gaillard teaches a liposome/probe composition as recited in instant claim 34, as this is the same composition taught in instant claim 18. However, none of these references teach a sensor as claimed in claim 34, though it is noted that Jakobsen does teach that their liposomal methods can easily be used with chip methods by immobilizing the liposomes and attached DNA (page 6993, column 1, para. 3).
Craighead teaches methods associated with microfluidic chips and their use in detection methods (Abstract and para. 3). The microfluidic device can contain fluid channels between an inlet and an outlet (para. 38). Each fluid channel can contain two or more separate chambers for different target molecules (para. 52). The reference also shows the use of positive controls (para. 33 and Figure 12A) and specifically states that a control chamber can be used (para. 53). Targets can be identified by their binding to macromolecules, such as liposomes (para. 64). Craighead specifically states that use of liposomes would require immobilization within a sol-gel matrix, where such a matrix can be a hydrogel (paras. 55 and 64). Use of fluorescent detection methods in the chip are also recited (e.g. paras. 86 and 90). The reference teaches that the use of this chip is high-throughput, can be multiplexed, and decreases time, sample volume, and cost (para. 19).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to combine the teachings of Craighead with those of Jiang, in view of Jakobsen, and in view of Gaillard to arrive at the sensors of claims 34-37. Craighead teaches many benefits of the use of their chip, and by incorporating the hydrogel-liposome composition of Jiang, in view of Jakobsen, and in view of Gaillard, it would allow for easier and more effective assaying with said composition. Craighead also teaches the use of multiplexing and control chambers, so multiple target groups and a control group could be analyzed simultaneously, allowing for more accurate results and the ability to analyze multiple samples quickly. The ordinary artisan would also be motivated to utilize the hydrogel-liposome composition of Jiang, in view of Jakobsen, and in view of Gaillard in the chip of Craighead, as hydrogels are one of the matrices taught by Craighead that would be needed in order for the liposomes to function. There would be a reasonable expectation of success as Craighead teaches that hydrogels and liposomes may be used in their chip, and teaches that fluorescence can be detected.
Thus, claims 34-37 are prima facie obvious over Jiang, in view of Jakobsen, in view of Gaillard, and further in view of Craighead.
Conclusion
No claims are currently allowable.
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.
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/F.F.G./Examiner, Art Unit 1681 /GARY BENZION/Supervisory Patent Examiner, Art Unit 1681
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