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.
Response to Restriction/Election
Applicant’s election of with traverse of Group I, claims 1-16 and 45-46 drawn to a composition, in response to restriction requirement of 09/08/2025, is acknowledged. Applicant’s election of an “microbeads” for a single species of a “substrate”, “glycan” as a single species of a “binding moiety”, “mannose and mannose derivatives” a single species of “glycan”, “bifunctional PEG compound” as a single species of a “spacer” , “peptide bond” as a representative species for “first bond” and “glycoside” as the species of “second bond”, is also acknowledged. Applicant’s traversal is on the ground that the groups are directed to a single inventive concept and therefore are linked inventions. The above arguments have fully been considered bur are not found persuasive. The technical feature is the composition of claim 1 which links Groups I-III and the composition of claim 1 comprises a glycan covalently linked to a chemically modified substrate through a cross-linker/spacer. However, as described in the restriction/election requirement mailed on 09/08/2025, the technical feature is disclosed in D1 (US 2007/0281865A1) and thus there is lack of unity a posteriori, since the technical feature is not a technical feature that defines a contribution over the prior art. In regards to Applicant’s traversal for election of species requirements, it is noted that under PCT Rule 13.2, the requirement of a technical interrelationship and the same or corresponding special technical features shall be considered to be met when the alternatives are of similar nature. Alternative chemical compounds shall be regarded as being of similar nature where the following criterial are fulfilled: (A) all alternative have a common property or activity; and (B) (1) a common structure is present, i.e., a significant structural element is shared by all of the alternatives; or (B) (2) in cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains. As described in the restriction/election requirement mailed on 9/8/2025, each of the “substrate”, “binding moiety”, “linker”, “glycan”, “spacer’, “first bond” and “second bond” as disclosed throughout the claims and as described in the specification, encompasses various divergent alternative structures wherein the alternatives are not of similar nature or common property and the alternative structures/compound does not have a common structure of significant structural elements shared by all alternative. The they are deemed to lack unity of invention.
Therefore, the restriction/election requirement is deemed proper and is made FINAL.
Therefore, claims 17 and 43 are withdrawn from further consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. Applicants preserve their right to file a divisional on the non-elected subject matter.
Status of the claims
Claims 1-16, 45 and 46 are examined on merits in this office action.
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 11, 13 and 14 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 14, which is dependent on the spacer of claim 13, recites “wherein the spacer is selected from the group consisting of 2-(2-(2-(2- aminoethoxy)ethoxy)ethoxy)ethanol (
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) or 4,7,10- trioxa-1,13-diaminotridecane (
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)”. The term “spacer” in the specification refers to any chemical moiety bound to the substrate which however, does not comprise a glycan binding moiety (page 16 of the specification). Specification recites “the wording “linker” refers to an at least bifunctional (bidentate) chemical moiety (i.e. a chemical moiety having at least two functional groups) capable of 'linking' a substrate with a binding moiety. The linker may act as a bridging group between the substrate and the binding moiety”. Claim 1 defined binding moiety comprising a glycan.
However, as claimed in claim 12 (which is directed to the linker) and claim 14 (which is directed to the spacer), the same compound 4,7,10- trioxa-1,13-diaminotridecane (
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) is claimed for a linker and for a spacer, which is confusing. The compound
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comprises two functional amine group (i.e. a bifunctional amine) (See claim 11, which claim bifunctional amine as linker) and thus claiming a bifunctional amine for spacer makes it confusing as to what compound is intended to encompass by the terms “linker” and “spacer” and how they are distinct in structures as defined in the specification. Moreover, the compound
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of claim 14 comprises two functional groups, an amine group and a hydroxyl group, which is also a bifunctional linker ( see the linkers 7-aminoheptanol, 10-aminodecanol of claim 12 linker, which comprises an amine group and a hydroxyl group). Thus it is unclear how is the linker is separate from the spacer as claimed.
Furthermore, claim 11 recites “a carboxylic acid” for linker. A carboxylic acid encompasses a single carboxylic group in the compound, which is contrary to the definition of “linker” in the specification as the specification defines “linker” as having at least two functional group. Thus, claiming of a carboxylic acid for the linker in claim 11, makes the claim confusing.
Claim 12 directed to some linkers for claim 1 linker and recites “carboxylated variants thereof”. “Carboxylated variant” has not been clearly defined or described in the specification and thus it is unclear what variants with carboxylic acid are intended for the cited compounds? As for example, replacing hydroxyl group or azide group of 2-azidoethanol or introducing additional carboxylic group on the compound 2-azidoethanol and if introducing additional hydroxyl group, at what position? There is direction or clear description for carboxylated variants and thus it is unclear what compounds are intended by carboxylated variants of the cited compounds by the recitation “carboxylated variants thereof”.
Claim 45 discloses a structure for the linker of claim 1 as copied below:
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. In the structure, R’ is not defined and thus it is unclear what compound is intended to represent by R’. Moreover, it is unclear what is intended for the wavy line in the structure as the wavy line has not been defined. Furthermore, last line of the claim recites “or combination thereof” and it is unclear combination with what compound with the structure in intended for by the recitation “or combination thereof”.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 6-11, 13, 15-16 and 46 are rejected under 35 U.S.C. 102(a1) as being anticipated by Blixt et al. (US2007/0281865A1; Cite # 1; IDS of 11/4/2022).
In regards to claims 1, 8 and 13, Blixt teaches that the invention related to a bi-functional spacer (i.e. linker) molecule with two reactive moieties, a first moiety with selected reactivity for attachment to the terminus of glycan amine molecules without significant alteration of the glycan structure and a second reactive moiety that facilitates linkage of spacer-derivatized glycans to other entities such as solid supports. Blixt teaches that the spacer molecules of the invention are therefore useful for making arrays of immobilized glycan molecules (Abstract and para [0010]). Blixt teaches that the solid support is chemically derivatized with various functional groups, as for example, NHS, amine (-NH2) and hydroxyl to provide a chemically derivatized substrate for immobilization of glycan probe (paragraph [0025]). Blixt discloses a glycan (i.e. binding molecule) array and kit composition comprising a chemically modified solid support (paragraphs [0022]; [0025] and [0149]) and a library of glycan molecules covalently attached to the solid support via a spacer (i.e. a linker) (para [0022] and claim 16).
In regards to claims 2, 3 and 10, Blixt teaches that glycan molecules are printed onto an N-hydroxysuccinimide derivative (NHS) derivatized solid support (claim 17 and Fig.1) and immobilization of glycans having amine group (-NH2) through an peptide bond (amide bond) (Fig. 1). It is noted that claim 1 is not limited to any type of bond and the peptide bond (amide bond) reads on the first bond or the second bond as claimed separately in claims 1 and 3.
In regards to claims 6, Blixt teaches derivatizing the solid surface with trialkoxysilane bearing reactive moieties such as NHS or amino (-NH2) group (paragraph [0025]).
In regard to claim 7, Blixt teaches mannose containing (para [0029]) and galactose containing (claim 18) glycans.
In regards to claim 9, Blixt teaches Neuraminic acid, N-acetylneuraminic acid, D-galactoronic acid, and D-glucoronic acid, which are considered as sugar acids (Table 1).
In regards to claim 11, Blixt teaches bifunctional spacer of Formula IB (see claim 1 of the reference) wherein R3 is an amine (see claim 3 of the reference).
In regards to claim 13, Blixt teaches ethanolamine for blocking remaining NHS group of the solid surface and ethanolamine would be considered as a spacer as ethanolamine binds to the substrate having the NHS group but does not bind to glycans.
In regards to claim 46, Blixt teaches defined glycan probe location each with one type of glycan molecules and the “one type of glycan molecules” employed can be a group of substantially structurally identical glycan molecules (paragraph [0063]).
In regards to claims 15 and 16, the cellular targets are considered not a part of the composition and the preamble “for detection of target cellular material” is considered as an intended method process utilizing the composition and since the composition as described above by Blixt are the same composition as claimed in claim 1, the composition of Blixt would be capable of detection of cellular targets. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In a claim drawn to a process of making, the intended use must result in a manipulative difference as compared to the prior art. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458, 459 (CCPA 1963).
Claims 1-8, 10-11, 15-16 and 46 are rejected under 35 U.S.C. 102(a1) as being anticipated by Galan et al. (WO2019/134897A1).
In regards to claim 1 Galan discloses a composition comprising a chemically modified amine substrate, a binding moiety comprising glycan and a linker covalently linked to the substrate and the binding moiety by a first and second bond (Example 13, page 29):
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. In the above scheme,
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is a chemically modified nanodot having an amine group (CND-NH2) ,
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is a binding moiety comprising glycan and succinic anhydride is a linker covalently linking to the substrate amine group and the amine group of the glycan
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. Therefore, the reference is deemed to anticipate claim 1 limitations as claimed.
In regard to claims 2, 3 and 10, as described above the succinic anhydride group links the substrate amine group through an amide and the amine group of the glycan through an amide bond and the amide bond is considered as a peptide bond because amino acids are conjugated in peptide through amide bonds.
In regards to claims 4-5, as described above, Galan discloses carbon nano dot (CND) chemically modified with amine group and the carbon nano dot is considered as a particle.
In regard to claim 6, as described above, Galan discloses carbon nano dot (CND) chemically modified with amine group.
In regards to claim 7, Galan discloses glucose functionalized CND (Examples 18 and 19) and lactose-CNDs (page 30, line 32) and instant claim 7 recites Glycan is Glc, or Lac.
In regards to claims 8 and 46, the process as disclosed in Galan (page 29, Example 13), would link plurality of the same glycan molecules through plurality of linkers absent showing otherwise by applicant.
In regards to claim 11, as described above, hydrolysis of succinic anhydride provides a carboxylic acid linker.
In regards to claims 15 and 16, the cellular targets are considered not a part of the composition and the preamble “for detection of target cellular material” is considered as an intended method process utilizing the composition and since the composition as described above by Galan are the same composition as claimed in claim 1, the composition of Galan would be capable of providing the intended process. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In a claim drawn to a process of making, the intended use must result in a manipulative difference as compared to the prior art. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458, 459 (CCPA 1963).
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 1-11, 13, 15-16 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Blixt et al. (US2007/0281865A1) alone or further in view of Purohit et al Nature communications).
Blixt has been described above anticipating the composition of claims 1-3, 6-11, 13, 15-16 and 46. Blixt teaches that the invention related to a bi-functional spacer (i.e. linker) molecule with two reactive moieties, a first moiety with selected reactivity for attachment to the terminus of glycan amine molecules without significant alteration of the glycan structure and a second reactive moiety that facilitates linkage of spacer-derivatized glycans to other entities such as solid supports. Blixt teaches that the spacer molecules of the invention are therefore useful for making arrays of immobilized glycan molecules (Abstract and para [0010]). Blixt teaches that the solid support is chemically derivatized with various functional groups, as for example, NHS, amine (-NH2) and hydroxyl to provide a chemically derivatized substrate for immobilization of glycan probe (paragraph [0025]). Blixt discloses a glycan (i.e. binding molecule) array and kit composition comprising a chemically modified solid support (paragraphs [0022]; [0025] and [0149]) and a library of glycan molecules covalently attached to the solid support via a spacer (i.e. a linker) (para [0022] and claim 16).
Blixt as described above teaches immobilization of Glycans on chemically modified solid substrate but does not mention immobilization of Glycans on a bead or a particle as claimed in claims 4 and 5.
However, Blixt describes that in some embodiment, the spacer of the invention also has a dye or a label (paragraph [0081]) and examples of dyes or labels that can be attached include fluorescent agents, enzymes, colloidal gold particles and colored latex particles. Therefore, attachment of various detectable particles including gold particles, gold nanoparticles, colored latex particles or colored beads to spacer of Blixt would be obvious to one of ordinary skilled in the art.
Purohit teaches glycan bead array for high throughput and high content analyses of glycan binding proteins. Purohit discloses conjugation of Glycans to beads using a bifunctional linker (Fig.1). Purohit teaches that Glycan arrays have been used in a variety of studies and have greatly enhanced our understanding of glycan functions. Purohit teaches flat surface glycan array is technically challenging and cannot be easily made available to non-experts and is difficult to translate flat surface microarray into a clinical tool due to the technical difficulties and long turn-around time of the assay and furthermore, the flat surface array does not allow rapid analyses of large numbers of samples required by many studies (page 3, 1st col.). Purohit teaches multiplex glycan bead array (MGBA), which is based on Luminex bead array technology and to create the MGBA, they covalently attach one glycan per bead region, creating a panel of 184 beads corresponding to 184 glycans used in this study. This high throughput and high-content platform allows rapid and economic analyses of large numbers (thousands) of glycans and large number of samples (thousands to tens of thousands). Purohit teaches carboxylated Luminex beads and immobilization of Glycan to beads using EDC activation (page 4, 1st col.). Purohit teaches that the manufacturing of the glycan-conjugated beads is a routine chemical reaction that can be adopted in almost all research and medical laboratories with basic training in biochemistry and immune assays. The assay uses inexpensive equipment that is certified for clinical use, requires small sample volume and has a relatively fast turnaround time, 4 h for lectin/anti-glycan antibodies assays and for measurement of anti-glycan antibodies in serum. Therefore, it can be easily adopted by medical laboratories for clinical services. Because of these advantageous attributes of MGBA, we believe that it will become a method of choice to investigate glycan-GBP interactions and significantly advance glycobiology (page 10, 2nd para of 1st col.).
Therefore, given the teaches of Purihit that utilizing bead instead of flat surface as solid support allows rapid and economic analyses of large numbers (thousands) of glycans and large number of samples, it would be obvious to one of ordinary skilled in the art to easily envisage utilizing Luminex beads and various other know beads, as for example, magnetic beads, latex beads, and microbeads for the solid support of Blixt, with the expectation of expanding the arsenal of solid support with rapid and multiplex analyses of samples with a reasonable expectation of success.
Conclusion
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678