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 .
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.
Status of Claims
Claims 1, 3, 5-13 and 19-27 are currently pending. Claims 8 and 11 are withdrawn. Claims 1, 3, 5-7, 9-10, 12-13 and 19-27 are under examination.
Withdrawn Objections/Rejections
In light of the amendments, the 35 U.S.C. 112(b) is hereby withdrawn.
In light of the amendments, the 35 U.S.C. 112(d) is hereby withdrawn
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.
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.
Claims 1, 3, 5-7, 9-10, 12-13 and 19-27 are rejected under 35 U.S.C. 103 as obvious over Dose (US2016/0347907A1, Application No. 14/723,505 was filed on 05/28/2015 (PTO-892 dated 05/08/2025), in view of Kotagiri et al. (“Antibody Quantum Dot Conjugates Developed via Copper-Free Click Chemistry for Rapid Analysis of Biological Samples Using a Microfluidic Microsphere Array System” Bioconjugate Chemistry, vol. 25, pgs. 1272-1281, published 06/09/2014), as evidenced by Creative PEGWorks, retrieved on 03/13/2026.
With respect to claims 1 and 19, Dose teaches that fluorescent dyes such as multi-arm polyethylene glycols are highly fluorescent without noticeable quenching (at para. [0015]). Dose also teaches in the claims the structures of the fluorescent dye conjugate:
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Emphasis added.
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Emphasis added.
Dose discloses in Example 1:
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As discussed above, Dose teaches using maleimide chemistry for conjugation an antibody with a branched PEG construct. Dose also teaches reactive groups R wherein the fluorescent dyes according to the invention are attached to biomolecules (i.e., antibody) via groups R, comprising a reactive group and Groups R shall be capable of forming covalent bonds via the reactive group of the biomolecule and the reactive groups may be active esters, maleimide, hydrazine, alkyne, or alkyl azide (at paras. [0049] and [0053]). Dose teaches the fluorophore F is cyanine dyes (at para. [0037]). Dose teaches the IgG antibody with 2 to 7 fluorescent polyether labels carrying each 4 to 6 fluorophore groups, resulting in fluorophore DOLs of 8 to 40 dye molecules per antibody molecule (at para. [0059]).
Dose does not teach each polymer has a molecular weight of about 10,000 Da (claim 1) or 20,000 (claim 19) nor exemplify the use of azide/alkyne chemistry, which is the elected species (a), a covalent attachment between an azide group of the antibody and a dibenzocyclooctyne (DIBO) group attached to a "20K8 PEG" linker as a mode of attachment of the fluorescent label to an antibody.
Kotagiri teaches an antibody-based technology for cancer diagnostic screening through quantum dot based fluoro-immunoconjugate (at abstract). Fig. 1 shows two reactions of an antibody with alkyne moiety through the reaction of the antibody with maleimide PEG DBCO or NHS PEG DBCO (dibenzocyclooctyne). Additionally, Fig. 1 shows an azide moiety conjugated to PEG spacer and through click reaction the antibody is covalently conjugated to the fluorescently labeled PEG polymer spacer. Kotagiri teaches employing click chemistry reaction through cycloaddition reactions and the rapid, specific, efficient, stable, facile, modular, and aqueous-phase conjugation strategy of click reaction has proven to be a reliable and powerful technique that is employed widely (at pg. 1273, left col., top of para. 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have conjugated together the multi-armed PEG polymer and antibody as taught by Dose through azide-alkyne cycloaddition reaction as taught by Kotagiri because (1) Dose already recognizes alkyne and azide as reactive groups for forming covalent bonds and discloses that a person will have no difficulty in selecting the appropriate chemistry with the reactive groups and (2) Kotagiri teaches that forming covalent bonds through azide-alkyne cyclcoaddition has proven to be a reliable and powerful technique that is widely employed for conjugation. Therefore, it would have been obvious to have employed the alkyne and azide reactive groups of Dose for cycloaddition reaction as taught by Kotagiri because the mechanism of cycloaddition reaction is selective between two recognized reactive groups in forming a reliable covalent bond that is widely employed and recognized. With respect to the elected species, it would have been obvious to the person to have attached azide with the antibody and dibenzocyclooctyne with the 8-Arm PEG of Dose because Kotagiri recognizes azide and dibenzocyclooctyne can be attached to individual PEG groups.
With respect to the functional recitation of fluorescent ratio, since the fluorescent dyes conjugated to the multi-armed polyethylene glyco polymers have the same structural elements as the instantly claimed fluorescently labeled multi-armed polyethylene glycol polymer, it would reasonably exhibit and possess the functional characteristics as claimed. In particular, Dose teaches the IgG antibody with 2 to 7 fluorescent polyether labels carrying each 4 to 6 fluorophore groups (at para. [0059]).
With respect to the limitations of molecular weight of about 10K Da or about 20K Da, Dose has recognized that the length of PEG is modifiable wherein n, m, or p is from 2 to 500 (see above). Meanwhile, the instant specification used PEG4 (see Tables). Because the range overlaps with the range disclosed by the prior art, a prima facie case of obviousness exists. Also, Creative PEGWorks has indicated that 8-Arm PEG has a MW 20K without fluorescent dyes.
Meanwhile, Applicant is reminded that, according to MPEP § 2112.01 “Product and apparatus claims — when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent”, or a prima facie case of obviousness has been established:
“Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp.v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).
See also In re Ludtke, 441 F.2d 660, 169 USPQ 563 (CCPA 1971) (Claim 1 was directed to a parachute canopy having concentric circumferential panels radially separated from each other by radially extending tie lines. The panels were separated “such that the critical velocity of each successively larger panel will be less than the critical velocity of the previous panel, whereby said parachute will sequentially open and thus gradually decelerate.” The court found that the claim was anticipated by Menget. Menget taught a parachute having three circumferential panels separated by tie lines. The court upheld the rejection finding that applicant had failed to show that Menget did not possess the functional characteristics of the claims.); Northam Warren Corp.v.D. F. Newfield Co., 7 F.Supp. 773, 22 USPQ 313 (E.D.N.Y. 1934) (A patent to a pencil for cleaning fingernails was held invalid because a pencil of the same structure for writing was found in the prior art.).” Emphasis in the original.
Also, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable in producing high quantum yield and fluorescence through a plurality of fluorescent labels and PEG linkers. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed how the molecular weight (MW) concentrations by itself in the claims affected the outcome function (e.g., reduce quenching). It would have been obvious for the person of ordinary skill to discover the optimum effective conjugate of PEG linkers with fluorescent labels to produce high quantum yield and fluorescence.
With respect to the elected species (a), Dose (at paras. [0007] and [0040]) teaches that it is particularly advantageous to use fluorescent dyes with sulfonate substituents, such as dyes of the Alexa fluor family provided by Thermo Fisher Scientific Inc. and that “The use of sulfonated dyes compared to unsulfonated dyes leads to even brighter conjugates of fluorophores multimerized on a polyether scaffold as can be seen in FIG. 2: T helper cells stained with a CD4 conjugate of Alexa Fluor 488 multimerized on a branched PEG (PEG-AF488).” Therefore, it would have been prima facie obvious for the person to have made and used the commercially available Alexa fluor family as taught by Dose to compare the degree of brightness in the conjugate.
The person would have reasonably expected success in using azide and alkyne as the reactive moieties for covalent attachments and 10K Da or 20K Da polymer because Dose recognizes PEG armed conjugates and azide and alkyne reactive groups and Kotagiri recognizes using azide and alkyne reactive groups in the presence of maleimide group.
With respect to claims 3 an 20, Dose teaches the IgG antibody with 2 to 7 fluorescent polyether labels carrying each 4 to 6 fluorophore groups, resulting in fluorophore DOLs of 8 to 40 dye molecules per antibody molecule (at para. [0059]).
With respect to claims 5 and 21, Dose does not teach an average brush distance of 200 to 800 angstrom as claimed. However, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable of degree of labeling an antibody for detection. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the limitations in claim 5 are for any particular purpose or solve any stated problem, and Dose teaches the results of degree of labeling the antibody with the 8-arm PEG polymer (see Example 1). Absent of unexpected results, it would have been obvious to the person of ordinary skill in the art to discover the distance between fluorescent labels on a multi-arm PEG to produce optimum degree of labeling results.
With respect to claims 6 and 22, Dose teaches in Figs. II and III that Z groups are separated with at least 16 covalent bonds, wherein Z is either a fluorophore F group or reactive R group to the antibody (at para. [0036] and Example 1).
With respect to claims 7 and 23, Dose teaches in Figs. II and III that Z groups are separated within 16 to 800 covalent bonds, wherein Z is either a fluorophore F group or reactive R group to the antibody (at para. [0036] and Example 1).
With respect to claims 9 and 24, Dose teaches the fluorophore F is cyanine dyes (at para. [0037]). Dose also teaches AF488 dye (at Example 1), which would read on a fluorescein dye derivative thereof.
With respect to claims 10 and 25, Dose teaches the fluorophore F is cyanine dyes (at para. [0037]). Dose also teaches AF488 dye (at Example 1), which would read on the labels comprising a moiety of xanthene or cyanine.
With respect to claims 12-13 and 26-27, Dose teaches the IgG antibody with 2 to 7 fluorescent polyether labels carrying each 4 to 6 fluorophore groups, resulting in fluorophore DOLs of 8 to 40 dye molecules per antibody molecule (at para. [0059]). Dose teaches in Fig. II of eight Z groups on the PEG conjugate, wherein Z has a plurality of fluorophore F groups or at least one reactive R group to the antibody (at para. [0036]).
Also, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable in producing high quantum yield and fluorescence through a plurality of fluorescent labels and PEG linkers. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed how the molecular weight (MW) concentrations by itself in the claims affected the outcome function. It would have been obvious for the person of ordinary skill to discover the optimum effective conjugate of PEG linkers with fluorescent labels to produce high quantum yield and fluorescence.
Response to Arguments
Applicant's arguments filed 07/22/2026 have been fully considered but they are not persuasive under 35 U.S.C. 103. Note that the rejection has been modified in view of Applicant’s amendments.
Applicant argues 6-9 that the recited four and eight -armed polyethylene glycol polymers were critical in achieving the unexpected superior results exhibited by Applicant’s conjugates. Applicant further argues that claim 1 exhibited superior reductions in quenching. Applicant argues that Dose merely provides a very broad genus of eight-armed polymers and does not provide any data or information motivating a POSITA to utilize eight-armed polymers having a molecular weight of about 20K.
The arguments are not found persuasive for the following reasons. To provide a showing of unexpected results, Applicant must provide claims that are commensurate in scope with the results that are provided form specification other than just the generically reciting the conjugated antibody with a MW of 10K Da or 20K Da. In particular, Applicant must show what is the structural construction of the PEG polymer having either 10K Da or 20K Da with generic fluorescent labels in the conjugate antibody that would reduce quenching to provide the superior results as claimed. Note that the written description was withdrawn based on the knowledge of the art and the Affidavit filed 12/17/2025.
With the knowledge, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable in producing high quantum yield and fluorescence through a plurality of fluorescent labels and PEG linkers. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed how the molecular weight (MW) concentrations by itself in the claims affected the function. It would have been obvious for the person of ordinary skill to discover the optimum effective conjugate of PEG linkers with fluorescent labels to produce high quantum yield and fluorescence.
Thus, Applicant has not provided claims that are commensurate in scope with the showing of the unexpected and/or superior results from the present application.
Conclusion
No claim is allowed.
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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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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