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 .
DETAILED ACTION
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 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.
Status of the claims
Applicant’s arguments and amendments filed 12/15/2026 is acknowledged. In the amendments, claims 2 and 12 have been canceled and thus claims 1, 4, 6, 8, 10, 14 and 16 are examined on merits in this office action. See office action of 8/15/2025 for the withdrawal of claims 3, 11, 17, 19, 21, 23, 25, 28-30 from further consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
Claim Rejections - 35 USC § 112
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 1, 4, 6, 8 and 10 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 1 introduces the limitation of divalent nitrobenzene derivative for P1 in the structure of formula (I). It is unclear what derivative of ortho-nitrobenzene is intended to encompass in the claim as derivative of nitrobenzene has not been defined or described in the specification. The only ortho-nitrobenzyl derivative disclosed throughout the application is a methoxy substitution on nitrobenzyl at para position relative to the nitro group (see claim 14). There are no other derivative disclosed or described in the specification and thus it is unclear as to what other derivatives are intended to encompass in the claimed formula (I) by the recitation “ortho-nitrobenzyl derivative”.
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 1, 4, 6, 8, 10, 14 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.
Claim 1 is directed to a photoreactive probe having the structure of Formula (I)
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As claimed, T is a recognition moiety capable of binding a first binding partner, L1 is a bivalent linker, P1 is a divalent ortho-nitrobenzyl derivative, P2 is a photoreactive moiety and R is a detectable moiety or a precursor thereof capable of binding a second binding partner. As claimed, the recognition moiety T encompasses an inordinately a large number of structurally and functionally distinct moiety. As for example, the target recognition moiety encompasses an antibody capable of binding to a protein, a nucleic acid capable of binding to complementary nucleic acid, a lectin capable of binding to a saccharide, an enzyme capable of binding to a substrate and so on. The detectable moiety R group encompasses various compounds, as for example, a detectable proteins, as for example, fluorescent proteins such as GFP and YFP, a detectable antibody capable of detection by binding to a fluorescent protein or other detectable group, a nucleic acid capable of detection by base paring with complementary nucleic acid and so on.
However, throughout the specification, probe comprising trivalent linker is very limited to having small molecules groups for target recognition moiety, and R group very limited to biotin or an alkyne. Throughout the specification, in all the disclosed probes, the T recognition molecule with trivalent linker is strictly limited to
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group (see claim 16 and pages 7-12). There is not a single example of a trivalent linker having orthonitrobenzyl wherein the T is other than the group as described above, as for example, an antibody, an enzyme, a lectin or other groups. Throughout the specification, in all the examples and disclosed structures having trivalent linker with orthonitrobenzyl, the detectable moiety R group is strictly limited to biotin and alkyne (see claim 16 and pages 7-12). There is not a single example of a trivalent linker having orthonitrobenzyl wherein the R is other than biotin or alkyne. There in no disclosed structure of clear description for R group wherein the R group a detectable protein, as for example, fluorescent proteins such as GFP and YFP or a detectable antibody.
MPEP § 2163 states that, for a claimed genus, the written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
Emphasis added.
As described above, there a substantial variation within the genus representing T, R and P2 and disclosing only one of two species of the genus cannot be considered disclosing sufficient variety of species to reflect the variation withing the genus.
Accordingly, the claims do not meet the written description provision of 35 USC 112(pre-AIA ), first paragraph with the scope of probe or prove system represented by the scope of compounds encompassed by each of T, R and P2 .
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 of this title, 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.
Claims 1, 4, 6, 8, 10, 14 are rejected under 35 U.S.C. 103 as obvious over Stewart et al. (Chemical Commun. 2015; Cite # 29 of NPL in the IDS filed 1/23/23) in view of Sefkow et al (WO 2012/156377; cite # 2, Foreign Patent Documents) and Chang et al (Bioorganic & Medicinal Chemistry 2016).
In regards to claim 1, Stewart teaches a photoactive chemical probe or probe system for proximity profiling of biological interactions (abstract, A bicyclo [6.1.0]nonyne (BCN)-based cyclooctyne reagent bearing a photocrosslinking diazirine (DAz) group and a biotin affinity handle, BCN-DAz-Biotin, is reported.
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BCN-DAz-Biotin is capable of simultaneously delivering photocrosslinking and affinity tags to azidelabeled biomolecules, enabling photoactivated capture and enrichment/detection of interacting species in native contexts.), wherein the photoactive chemical probe or probe system comprises a target recognition moiety capable of specifically binding a first binding partner associated with a biological target of interest (BTOI), optionally wherein the first binding partner is a peptide or-protein tag attached to the BTOI (pg 17601, col 2, para 1, First, M. smegmatis was treated with 6-TreAz, leading to efficient azide-labeling of glycolipids. The cells were then reacted with varying concentrations of BCN-DAz-Biotin (1-100 mM) for 30 minutes followed by incubation with avidin-488. Analysis of cellular fluorescence confirmed that BCN-DAz-Biotin was delivered to glycolipids in an azide- and concentration-dependent manner (Fig. 2).); a detectable moiety or precursor thereof (pg 17602, col 1, para 1, The ligation product was then incubated with BSA and irradiated at 365 nm for 20 min (or left non-irradiated). SOS-PAGE followed by in-gel fluorescence analysis confirmed that photocrosslinking occurred between BCN-DAz-Biotin and BSA only when exposed to UV light.); and at least one photoactive moiety (Fig. 1, photocrosslinking diazirine.). Thus, Stewart teaches a photoactive probe having a structure of Formula (I): T-L2-(P2)(R); wherein:
T is a target recognition moiety capable of specifically binding a first binding partner (Fig. 1 B, BCN-DAZ-Biotin; the biotin moiety),
L2 Is a trivalent linker moiety (Fig. 1 B, BCN-DAZ-Biotin; the lysine scaffold);
P2 is a photoreactive moiety (Fig. 1 B, BCN-DAZ-Biotin; the diazine moiety); and
R is a detectable moiety or a precursor thereof (Fig. 1 B, BCN-DAZ-Biotin; the azide-reactive cyclooctyne moiety; Fig. 3, N3-Az488.)
Stewart however, do not teach that there are at least two photoactive moieties, wherein one of said photoactive moieties is a photocleavable or photocatalytic moiety.
Sefkow teaches a photoactive chemical probe or probe system for proximity profiling of biological interactions (abstract, a method for separating protein molecules, and compounds for use therein. A sample is contacted with a first compound of general formula (I): (Y-S-)(X -S-)-2-S-D.; pg 6, In 10-26, In one embodiment, X is an aryl trifluoromethyl diazirine or alkyl diazirine, an aryl azide or a benzophenone. The selectivity function Y in principle may be any molecular moiety with affinity to target (off- target-) proteins in the micromolar, nanomolar or sub-nanomolar range. Interaction of Y with a target protein will restrict linkage of the first compound (I) to certain proteins . The reactivity function X upon activation forms a covalent bond to any protein in its proximity. The selectivity function restricts the linkage of the capture compound to such proteins that specifically interact with the selectivity function Y.) comprising at least two photoactive moieties, wherein one of said photoactive moieties is a photocleavable or photocatalytic moiety (pg 3, In 7-19, Subsequent to said first binding step, said mixture is contacted with a second compound (II) described by a general formula E-S-F-S-Q in a second binding step, F is cleaved by exposure to light, thereby severing the covalent link between the (target/off-target) protein and a, and in a second isolation step, removal of molecules comprising Q from the reaction fraction renders isolated proteins.).
Chang teaches photoactive chemical probe comprising a target recognition moiety (e.g. galactose; i.e. a ligand) capable of specifically binding a first binding partner associated with a biological target of interest (BTOI), and a binding partner (e.g. cyclooctyne) capable of binding to complementary azide binding group:
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Chang teaches utilization of the probe for specific binding to target via the ligand and cross-linking via diazirine photolabile group for covalent capture of the protein complex (Abstract) Change teaches conjugating the crosslinked probe to a biotin having a photocleavable linker through the alkyne group of the probe
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, which enable specific presentation of the conjugate on streptavidin coated beads, and the photolabile linker allows the release of the labeled proteins (Abstract and Fig. 1).
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Therefore, from the description in mind of Stewart, Sefkow and Chang, it would have been obvious to one of ordinary skill in the art to have applied a photocleavable linker linking the target protein, which is released from the complex following photocleavage allowing subsequent isolation of photocrosslinked protein. Note that biotin can also be considered as a detectable moiety as biotin allows detection utilizing streptavidin containing fluorescent moiety or fluorescent beads. Chang teaches photocleavable site
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and since the basic concept of specific binding, cross-linking by photoactive group and separation utilizing complementary binding groups including utilizing photocleavable linkage has been described in the references, one of ordinary skilled in the art can easily envisage introducing the site at different position of the probe for optimization and depending on the need with a reasonable expectation of success. Since Stewart teaches biotin probe BCN-DAz-Biotin and since change teaches photocleavable linker in biotin probe useful for immobilization on avidin surface and release of labeled protein or target molecules, one of ordinary skilled in the art from the description in mind of the references, can easily envisage introducing the photocleavable site in the trivalent linker of Stewart with the expectation of expanding the arsenal of trivalent linker probe useful for target isolation and release with a reasonable expectation of success.
In regards to claims 4 and 6, as described above, the probes as described above comprises biotin and alkyne.
In regards to claim 8, as described above, stewart and Chang discloses diazirine for photoactive photolabile group for covalent cross-linking.
In regards to claim 10, Chang discloses linker comprising -NH-C(=O)-alkylene (Fig.1 (b)) and Stewart also teaches linker comprising -NH-C(=O)-alkylene.
Claim 16 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Response to argument
Applicant's arguments and amendments filed 12/15/2026 have been fully considered but are persuasive to overcome the rejection under 35 USC 103. Moreover, Applicant’s amendments necessitated modifying the rejection to address amendments and applying new grounds of rejection under 35 USC 112(a) as described above.
In regards to rejection under 35 USC 103, Applicant argued that claim 1 has been amended to recite the subject matter of claim 2 and recite the P1 comprises a divalent ortho-nitrobenzyl derivative and thus the cited combinations of the reference are not believed to support the rejection under 35 USC 103 with respect to presently presented claim 1. Applicant argued that the presently disclosed subject matter provides in some embodiments a strategy, including methods and compositions, that can be used to profile biological interactions, e.g., protein-protein interactions, protein-metabolite interactions, protein-drug interactions, cell-cell interactions, nucleic acid-drug interactions, etc. The strategy can be used to profile such interactions in or on live cells, which can serve to eliminate biases against low concentration biological entities, weak interaction affinities, and false-positive interactions caused when studying biological interactions in lysed cells. Thus, this strategy, as reflected in claim 1, is believed to represent a novel and inventive advance over the cited art of record. Indeed, as set forth above, it is respectfully submitted that the presently claimed subject matter cannot be provided with a reasonable expectation of success based upon the cited combination of references. Indeed, it is respectfully submitted that the cited combinations of references at best provide recognition of unsolved problems in the field without sufficient guidance that they might be combined as suggested by the Patent Office with a reasonable expectation of success. Applicant argued that the cited combinations of the references provide merely and invitation to experiment that without the use of impermissible hindsight would not have led one of ordinary skill in the art to instantly claimed subject matter.
The above arguments have fully been considered but are not found persuasive to overcome the rejection. Claim 1 is a product claim directed to a compound/conjugate represented by Formula (I) and is not a process claim. If the product is obvious from the combination of the references, then it meets the limitation. The references may be combined for a different reason than Applicant’s. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) (“One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.”). See also In re Linter, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972); and In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). In the instant case, the motivation arises from the fact the from Stewart’s disclosure, one of ordinary skilled in the art clearly sees a probe having trivalent linker having three functional moieties, a photoreactive moiety (diazirene), a biotin moiety that can be considered a detectable moiety or a moiety capable of binding to complementary binding partner, as for example, avidin and an affinity group (alkyne group) capable of binding/detection/enrichment to corresponding azide containing biomolecules. Sefkow discloses capture compound biotin linked to azide through a light cleavable ortho-nitrobenzyl group
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(scheme 3). Sefkow teaches that capture compound is for capturing protein an biotin can be utilized as sorting function, which binds to streptavidin and capture protein can be isolated from mixture by attachment to streptavidin-coverd magnetic particle which allows for the captured proteins' selective and careful disassociation from the matrix by cleaving the cleavable group. Chang also discloses biotin capture probe having cleavable linker for capturing and isolating capture protein by cleaving the cleavable moiety. Chang discloses capture probe
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having the photo cleavable moiety.
Therefore, from the description in mind of Seflow and Chang, one of ordinary skill in the art can readily understand the by introducing a photocleavable moiety/photocleavable site in a biotin containing probe, one can utilize the probe for isolation/enrichment of target protein immobilization and selective cleavage. Since Stewart teaches biotin probe BCN-DAz-Biotin and since Seflow and Chang teach photocleavable linker in biotin probe useful for immobilization on avidin surface and release of target molecules, one of ordinary skilled in the art from the description in mind of the references, can easily envisage introducing the photocleavable site in the trivalent linker of Stewart with the expectation of expanding the arsenal of trivalent linker probe useful for target isolation and release with a reasonable expectation of success.
A person of ordinary skill in the art, using common knowledge and common sense, is capable of fitting the teachings of multiple references together like pieces of a puzzle, regardless of the specific problem being addressed by the individual references. A person of ordinary skill in the art is also a person of ordinary creativity. obviousness can only be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See: In re Nomiya, 184 USPQ 607 (CCPA 1975); In re Fine, 837 F.2d 1071, 5USPQ2d 1596 (Fed. Cir. 1988); or, In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir.1992). However, there is no requirement that a motivation to make the modification be expressly articulated. The test for combining references is what the combination of disclosures, taken as a whole, would suggest to one of ordinary skill in the art. See: In re Keller, 642 F.2d413,208 USPQ 871 (CCPA 1981); or, In reMcLaughlin, 170 USPQ 209 (CCPA 1971).References are evaluated by what they suggest to one versed in the art, rather than by their specific disclosures. See: In re Bozek, 163 USPQ 545 (CCPA 1969). In this case, for the reasons of record, ample motivations to combine the references has been set forth and the combination of the reference provides obviousness of the probe compounds having the divalent ortho-nitrobenzyl cleavable moiety as claimed.
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 SHAFIQUL HAQ whose telephone number is (571)272-6103. The examiner can normally be reached on Mon-Fri 8-4:30.
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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