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 .
Status of the Claims
Claim 1-6 are pending and examined herein.
Withdrawn Rejections/Objections
The previous objection of claims 3, 4, and 6 is withdrawn in response to Applicant’s amendments to the claims.
The previous rejection of claims 1 and 6 under U.S.C. 112(b) is withdrawn in response to Applicant’s amendments to the claims.
The previous rejection of claim 3 under U.S.C. 103 is withdrawn upon further consideration and in view of Applicant’s arguments.
Priority
This application, filed 10/14/2021, is a 371 of PCT/EP2019/060403 filed on 04/23/2019. This priority is acknowledged and the claims examined herein are treated as having an effecting filing date of 04/23/2019.
Information Disclosure Statement
The Information Disclosure Statement filed 08/15/2025 is acknowledged and has been considered.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by WO 2007/109364 A2 (published 09/27/2007, herein referred to as Weissleder) for reasons of record which are reiterated herein below.
Regarding claim 1, Weissleder teaches a conjugate (Abstract, p. 3, line 23) with a backbone comprising an antigen recognizing moiety (p. 13, lines 29-31, “backbone comprises…antibodies”), an enzymatically degradable spacer (p. 14, lines 24-25) linked to fluorochromes (p. 14, lines 22-24). Weissleder teaches that conjugates have polyethylene glycol (PEG) solubility enhancing groups (p. 15, lines 20-22) linking the fluorochrome to the conjugate (p. 16, lines 2-4). Weissleder teaches PEG chain lengths of 1, 2, and 3, which anticipate the claimed linker units of “one or more” PEG residues (p. 15, lines 30-32). Further, Weissleder teaches that increasing PEG chain length “results in weaker dye aggregation and…higher fluorescence background” (p. 50, lines 25-26) indicating that conjugates with longer PEG chains lack intramolecular quenching and are fluorescent in the absence of enzymatic cleavage of the conjugate. Weissleder teaches that all of the components of the are covalently linked together in the following order: backbone – degradable spacer – PEG chain – fluorophore (Figure 1). Weissleder teaches that the enzymatically degradable spacer can be a polysaccharide or a nucleic acid (p. 14, lines 24-25).
Regarding claim 2, Weissleder teaches that the solubility enhancing groups can comprise PEG with a different polymer such as polyamidoamine, which is a polyamino group (p. 15, lines 28-30).
Regarding claim 3, Weissleder teaches the linker can comprise PEG residue lengths of 2 and 3 (p. 15, lines 30-32) which anticipates the claimed range of 2-500.
Regarding claim 4, Weissleder teaches that the antigen recognizing moiety can be an antibody or fragmented antibody (p. 13, lines 29-31) or nucleic acids (p. 13, lines 21-22).
Regarding claim 5, Weissleder teaches that the fluorescent moiety can be xanthene dyes (p. 23, lines 24-25), rhodamine dyes (p. 17, line 32), and cyanine dyes (p. 19, line 23).
Regarding claim 6, Weissleder teaches that a fluorescent moiety can be attached in a single polypeptide side chain (p. 14, lines 34-36) covalently attached to the backbone (p. 14, line 38) without a PEG linker.
Claims 1, 2, and 4-6 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US 2016/0187326 A1 “CELL DETECTION WITH CONJUGATES HAVING AN ENZYMATICALLY RELEASABLE DETECTION MOIETY” (published 06/30/2016, herein referred to as Dose) for reasons of record which are reiterated herein below.
Regarding claim 1, Dose teaches a conjugate (Abstract. Para. 0018, line 1) with an antigen recognition moiety (para. 0018, line 1-4), an enzymatically degradable spacer (para. 0018, lines 1-3), a fluorescent moiety (para. 0037, lines 1-4), and a linker (para. 0046, lines 8-10) comprising a polyethyleneglycol residue (para. 0047, lines 9-11, “succinimidyl-[(N-maleimidopropionamido) polyethyleneglycol] esters (NHS-PEG-MAL)”). Dose teaches that the components of this conjugate are covalently linked (para. 0031, lines 1-3), including the linker (para. 0046, lines 8-10), in the following order: antigen recognition moiety – degradable spacer – linker – detection moiety. Dose teaches that the enzymatically degradable spacer can be “polysaccharides,…polyesters, nucleic acids, and derivatives thereof” (para. 0049, lines 4-6).
Regarding claim 2, Dose teaches modification of the degradable spacer with amino groups (para. 0051, lines 4-6) upon which the linker (para. 0047, lines 9-11, “succinimidyl-[(N-maleimidopropionamido) polyethyleneglycol] esters (NHS-PEG-MAL)” would be attached via the NHS functional group.
Regarding claim 4, Dose teaches that the antigen recognizing moiety can be an “antibody, fragmented antibody, or fragmented antibody derivatives” (para. 0055, lines 1-3) and “peptide/MHC-complexes targeting TCR molecules, cell adhesion receptor molecules, receptors for costimulatory molecules, artificially engineered binding molecules, e.g., peptides or aptamers” (para. 0055, lines 12-15).
Regarding claim 5, Dose teaches that the fluorescent moiety can be “polymeric, such as polyfluorenes, small organic molecule dyes, Such as xanthenes, like fluorescein, or rhodamines, cyanines, oxazines, coumarins, acridines, oxadiazoles, pyrenes, pyrromethenes” (para. 0039, lines 2-5).
Regarding claim 6, Dole teaches that the fluorescent moiety can be attached via covalent bond (para. 0046, lines 1-5) to the enzymatically degradable spacer without the use of the linker.
Response to Arguments
Applicant's arguments filed 08/15/2025 have been fully considered but they are not persuasive for the following reasons:
Regarding the rejection of the claims under 35 U.S.C. 102 over Weissleder, on page 7 Applicant argues that claims 1 and 2 of Weissleder does not anticipate the conjugate of the instant application.
This argument is not persuasive. The entirety of Weissleder’s disclosure is considered for analysis of anticipation. In particular, Weissleder does disclose a conjugate with an antigen-recognizing moiety in the claimed covalent configuration. Weissleder teaches a conjugate (Abstract, p. 3, line 23) with a backbone comprising an antigen recognizing moiety (p. 13, lines 29-31, “backbone comprises…antibodies”), an enzymatically degradable spacer (p. 14, lines 24-25) linked to fluorochromes (p. 14, lines 22-24) See grounds of rejection under U.S.C. 102 above.
Regarding the remarks at page 7, Applicant argues that the conjugate of Weissleder has a protease-cleavable spacer, but fails to disclose a polysaccharide, polyester, or nucleic acid spacer that is degradable by enzymes. Applicant recognizes that Weissleder mentions a polysaccharide or nucleic acid spacer (p. 14, lines 24-25) but argues that Weissleder does not teach their cleavage.
This argument has been fully considered but is not persuasive. Weissleder teaches “a spacer molecule is a peptide, oligopeptide, polysaccharide, a nucleic acid, or a synthetic cleavable moiety” (p. 14, lines 24-25). Examiner interprets this statement to be a list of cleavable moieties, i.e. a peptide cleavable moiety, an oligopeptide cleavable moiety, a polysaccharide cleavable moiety, etc; therefore, Weissleder does disclose a cleavable polysaccharide and cleavable nucleic acid spacer as claimed.
Regarding the remarks at page 7, Applicant argues that the disclosure of 1, 2, or 3 PEG units in the conjugate of Weissleder does not anticipate the range of 2 to 500 PEG units of claim 3.
This argument is not persuasive. The disclosure of 2 or 3 PEG units falls squarely within the range of 2-500 PEG units and clearly anticipates the claimed range of 2-500. “[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (citing In re Petering, 301 F.2d 676, 682, 133 USPQ 275, 280 (CCPA 1962)) (emphasis in original)” See MPEP 2131.03.
Regarding the rejection of the claims under 35 U.S.C. 102 over Dose, on page 8 Applicant argues that the conjugate taught by Dose does not anticipate the claimed invention because Dose teaches that the conjugate fluoresces after cleavage whereas the claimed invention fluoresces before cleavage due to the PEG linker.
This argument is not persuasive. The claimed apparatus is examined on the merits of its structure alone. Any structure that satisfies the claims is assumed to function or be capable of functioning in a manner consistent with the claimed invention. Additionally, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the feature upon which applicant relies (i.e., the fluorescence of the conjugate before cleavage) is not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Regarding the argument on p. 8 that Dose does not teach a non-protease-cleavable spacer. This is not persuasive. Dose does teach “suitable as enzymatically degradable spacer P are, for example, polysaccharides, proteins, peptides, depsipeptides, polyesters, nucleic acids, and derivatives thereof” (para. 0049, lines 3-6).
Upon reconsideration and in view of Applicant’s arguments on p. 8 regarding the rejection of claim 3 under 35 U.S.C. 103, the rejection is withdrawn.
For the reasons above, the claims remain rejected and no claims are allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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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/C.E./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 August 28, 2025