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
This office action is a response to applicant’s communication submitted March 7, 2026, wherein claims 1, 5, 17, and 21 are amended and claim 18 is canceled. This application is a continuation of US application 16/183583, now US patent 11780863, filed November 7, 2018, which is a continuation of US application 15/246430, now US patent 10168336, filed August 24, 2016, which is a continuation of PCT/EP2015/053556, filed February 20, 2015, which claims benefit of provisional application 61/943940, filed February 24, 2014.
Claims 1-5, 9-13, 15-17, and 19-25 are pending in this application.
Claims 1-5, 9-13, 15-17, and 19-25 as amended are examined on the merits herein.
Withdrawn Rejections
Applicant’s amendment, submitted March 7, 2026, with respect to the rejection of claims 1-4 under 35 USC 112(b) for including the word “and” in what appears to be an alternative listing, has been fully considered and found to be persuasive to remove the rejection as the claims have been amended to replace “and” with “or”. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted March 7, 2026, with respect to the rejection of claims 18 under 35 USC 112(d) for failing to include all of the scope of base claim 17, has been fully considered and found to be persuasive to remove the rejection as claim 18 has been canceled. Therefore the rejection is withdrawn.
Applicant’s arguments, submitted March 7, 2026, with respect to the rejection of claim 1 under 35 USC 102(a)(1) for being anticipated by Jerussi et al., have been fully considered and found to be persuasive to remove the rejection as claim 1 does in fact require that n be at least 2. Therefore the rejection is withdrawn.
Applicant’s arguments, submitted March 7, 2026, with respect to the rejection of claim 1 under 35 USC 102(a)(1) for being anticipated by Davioud et al., have been fully considered and found to be persuasive to remove the rejection as claim 1 does in fact require that n be at least 2. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted March 7, 2026, with respect to the rejection of claim 5 under 35 USC 102(a)(1) for being anticipated by Cincotta et al., has been fully considered and found to be persuasive to remove the rejection as claim 5 has been amended to specify the identity of LG. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted March 7, 2026, with respect to the rejection of claims 17, 18, and 20 under 35 USC 102(a)(1) for being anticipated by Tsai et al., has been fully considered and found to be persuasive to remove the rejection as claim 17 has been amended to require that the sugar be selected from one of a number of sugars not including glucose. Therefore the rejection is withdrawn.
Applicant’s amendment, submitted March 7, 2026, with respect to the rejection of claims 21, 23, and 24 under 35 USC 102(a)(1) for being anticipated by Renoux et al., has been fully considered and found to be persuasive to remove the rejection as claim 17 has been amended to require that the linker RR be a chemical moiety other than a direct bond. Therefore the rejection is withdrawn.
The following rejections of record in the previous office action are maintained:
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.
Claim 5 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chu et al. (Reference of record in previous action)
Claim 5 is directed to a compound having a specific structure including a core phenyl ring with several attachments, in particular a cyclic phosphodiester. Chu et al. discloses the compound:
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(p. 2842 figure 1) This compound can be seen as falling within the first structure pictured in claim 5, wherein R10 is R3R4, with R3 being a bond and R4 being the rest of the molecule which is a fluorophore due to the presence of the FMOC group. Therefore Chu et al. anticipates claim 5.
Response to Arguments: Applicant’s arguments, submitted March 7, 2026, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant argues that Chu does not describe a group “LG” which is a halide, azide, or sulfate ester. However, the formula
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recited in claim 5 does not include the group LG. Therefore the amendment made to the identity of LG is not relevant to whether the compound described by Chu anticipates the present claims. Applicant further argues that Chu’s compounds are not described as quinine methide precursor compounds. However, what is objectively claimed is a particular structure, not the structure’s intended use or properties. Any compound falling within the scope of the claimed structure anticipates the claim, whether or not the art describes it as a quinine methide precursor.
For these reasons the rejection is deemed proper and maintained.
Claims 17, 19, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhu et al. (NPL reference 2 cited in 8/11/2023 PTO-1449) as evidenced by Jia et al. (Reference of record in previous action)
Independent claim 17 is directed to compound (VI) which comprises a phenyl ring attached to an enzymatically cleavable group, a methine bearing a leaving group, and a detectable label. Dependent claims 18 and 20 further define the identities of the variables R3 and LG in this structure.
Zhu et al. discloses a fluorescent activity-based probe targeting phosphatases. (p. 2669 figure 1, p. 2670 scheme 1) This compound has the same substituted phenyl structure recited in present claim 17. Furthermore the phosphate group falls within the scope of enzyme cleavable groups recited in the present claims, the fluoromethylene group falls within the scope of leaving groups, and the Cy3 and attached linking structure falls within the scope of detectable labels or chromophores recited in the present claims. Regarding the group R3 recited in claim 17, the structure described by Zhu et al. falls within an embodiment wherein R3 is C(O)N(H)(CH2CH2O)n, for example, and the fluorophore is -CH2CH2N(H)C(O)-Cy3. Regarding claim 19, Jia et al. confirms that the absorption spectrum of Cy3 is between 500 and 600 nm, which is within the visible spectrum, making this molecule a chromophore. (see p.1594 figure 1) Therefore Zhu et al. anticipates the claimed invention.
Response to Arguments: Applicant’s arguments, submitted March 7, 2026, with respect to the above ground of rejection, have been fully considered and not found to be persuasive to remove the rejection. Applicant argues that the examiner’s interpretation of which parts of the structure fall within “R3” and “R4” is improper, and that the structure must be interpreted in such a way as that the portion of the structure mapped to “R3” is not one of the specific definitions of R3 recited in claim 17. However, this is an overly narrow reading of the claimed structure. As written, R4 is defined in claim 17 as a detectable label, with no further structural or functional limitation. As written, pretty much any conceivable chemical structure could fall within the scope of R4. Seen in this context, the structure -CRa(LG)-R3R4 appearing in claim 17 is, in its broadest reasonable interpretation, infringed by any structure wherein the atoms most directly connected to the carbon atom in -CRa(LG)- compose one of the specific structures recited for R3, regardless of whether or not the chemical structure contains further atoms which bear resemblance to an embodiment of R3 previously canceled form this claim. So long as R4 is not given a limiting structural definition, any reallocation of structural elements between R3 and R4 is appropriate.
Furthermore upon additional consideration, so long as R3 is defined as including “a bond” as one option, any chemical structure at that position could be interpreted as infringing the claims, being simply a bond connecting a detectable label to the methide carbon atom.
Applicant further argues that the fluoro group appearing in Zhu’s structure somehow does not fall within the leaving group “LG” appearing in formula (VI) in claim 7. Applicant repeats the following argument:
Applicant further submits that the Patent Office's "fluoromethylene" leaving group theory does not establish the claimed "LG" limitation arranged as in Formula (VI). (Id.). The Patent Office asserts that "the fluoromethylene group falls within the scope of leaving groups" and cites Zhu's Scheme 1. Applicant understands the Patent Office to be relying on Zhu's reported alcohol- to-fluoride conversion (using DAST) as support for the presence of a fluoride-related feature in Zhu. However, Zhu's description of that synthetic conversion does not, by itself, establish that Zhu discloses a leaving group "LG" located at the methine carbon and arranged as required by Formula (VI). Indeed, the claim requires a leaving group "LG" in a specific structural position within the Formula (VI) scaffold. A synthetic step used to prepare a probe does not substitute for disclosure of the claimed "LG" limitation arranged as in the claim.
It is unclear how this argument relates to present claim 17 or to the rejection made above, as it appears to assume that Zhu does not disclose a structure containing a fluorine atom. The rejection does not rely on the alcohol-to-fluoride conversion in scheme 1 for disclosure of the leaving group. Rather, the product of scheme 1 in Zhu’s disclosure is Probe 1:
. This compound has a fluoro group attached to the methine directly attached to the phenyl ring. This fluorine atom falls within the scope of “LG” as it appears in this claim. This interpretation is supported by p. 7 lines 10-17 of the specification, which states:
LG may be any suitable leaving group, such as a halide, sulfate ester, carboxylate, inorganic ester, thiolate, amine, aryloxy, alkoxy, or heteroaryl. In some embodiments, LG is fluoride, chloride, azide, acetate, methoxy, ethoxy, isopropoxy, phenoxide, -OS(O)2CH3, -OS(O)2C6H4CH3, -OS(O)2C6H5, -OS(O)2C6H4CX3, -OC6H5, -N2+, -NH3+, -NC5Hs*, -O-alkyl, -OC(O)alkyl, -OC(O)H, -N(R)3+ or 1,4- diazabicyclo[2.2.2]octane (DABCO),”
From this passage it is clear that as defined in the present specification, a fluorine atom attached to a methylene carbon is a leaving group. Because claim 17 is directed to a chemical compound and not to a method of carrying out a chemical reaction, it is irrelevant to questions of anticipation whether a particular reference that teaches a claimed structure also describes the same functional limitations recited in the present claims.
For these reasons the rejection is deemed proper and maintained.
The following new grounds of rejection are introduced:
Claim Rejections - 35 USC § 112
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.
Claim 11 is 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 11 depends from claim 5, and contains a limitation further defining the group “LG” as one of 21 different chemical structures. However, as currently amended, the base claim 5 defines LG more narrowly, as only a halide, azide, pr sulfate ester. Since claim 11 allows for LG to have other structures besides these three, for example acetate, alkoxy, phenoxy, or amino, claim 11 fails to include all of the limitations of claim 5. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 17 and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lo et al. (Reference included with PTO-892)
Independent claim 17 is directed to compound (VI) which comprises a phenyl ring attached to an enzymatically cleavable group, a methine bearing a leaving group, and a detectable label. Dependent claim 20 further define the identity of the variables LG in this structure.
Lo discloses the compound
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R = dansyl
R = biotinyl (p. 38 scheme 2)
This compound anticipates claim 17, for reasons similar to those recited previously with respect to the reference Zhu et al. It is further remarked that structural fragments containing either Dansyl or biotinyl are detectable labels according to claim 17.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shen Yumei et al. (Foreign publication CN104292117A, Reference and English machine translation included with PTO-892, herein referred to as Yumei)
Independent claim is directed to a compound of the following formula (III):
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Shen Yumei discloses an acid-sensitive linking unit for use in DNA sequencing. (p. 10 paragraph 6) The linker is an acetal linker having the formula:
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. (p. 10 paragraph 9) In a specific embodiment the full conjugate has the structure:
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. (p. 66 paragraph 554) Considering that claim 1 allows for -Z-R1 to be lower alkoxy, the methoxy groups are reasonably considered to be embodiments of -Z-R1. The left portion of the molecule containing the nucleotide:
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is reasonably considered to be a substituted alkoxy, and therefore within the scope of “LG”. The right portion of the molecule:
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is reasonably considered to be an embodiment of -R3R4 wherein R3 is -O-(CH2)2-NH- and R4 is a fluorophore. Therefore Yumei anticipates the present claims.
It is further noted that Yumei has a publication date of January 21, 2015. While the present application claims benefit of provisional application 61/943,940, filed February 24, 2014, a review of the disclosure of 61/943,940 indicates that this provisional application does not provide written description under 35 USC 112(a) for claim 1 as presently pending. In particular, while the provisional application discloses generic structures such as
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, (top of p. 3) and several specific embodiments
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, (p. 16 paragraphs 62-63) none of these structures describe the essential feature of present claim 1 wherein a -Z-R1 and a -C(LG)(R5)(R3R4) are o- or m- oriented with respect to one another. Therefore the effective filing date of present claim 1 is seen to be February 20, 2015, and Yumei is properly applied as prior art.
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, 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 21, 23, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Graham. (US pre-grant publication 2006/0003383, cited in PTO-892)
Independent claim 21 claims a compound having a structure selected from one of two options including:
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. Dependent claims 23 and 24 further define the identities of -Z-R1 as a sugar moiety. Dependent claim 25 defines the structure of the fluorophore.
Graham discloses a substrate for detecting a molecule of interest comprising a hydrophobic moiety, a fluorescent moiety, and a trigger moiety, wherein activation of the trigger induces a spontaneous rearrangement which causes the release of one of the hydrophobic or fluorescent moiety. (p. 1 paragraph 4) In a particular embodiment the trigger is cleaved by a specific enzyme, for example a carbohydrate cleaved by a galactosidase or glucuronidase, for example a glucuronyl or galactosyl. (p. 1 paragraph 10, p. 13 table 2) In a particular embodiment the three moieties are attached to a central phenyl ring, similar to the structure recited in present claim 21. (p. 12 paragraph 124) According to p. 17 table 5, one of the possible arrangements of moieties is
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wherein -L-T is the trigger moiety that can be the sugar, D is the dye, and R is the hydrophobic moiety which can in this invention be considered to function as the leaving group LG in the structure of present claim 21. (See also p. 18 paragraph 150) Specific compounds described include:
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, which is described in figure 8B of Graham. This compound differs from the compound of present claim 25 in that it has the hydrophobic leaving group in the o- position and the fluorescent group in the p-position. However, it would have been obvious to one of ordinary skill in the art at the time of the invention to make a derivative of the aforementioned compound wherein the fluorescent group is at the o- position and the hydrophobic leaving group is at the p- position, as recited in present claim 21. One of ordinary skill in the art would have seen the disclosure of Graham as suggesting that either of these functional groups could be in either of these positions.
Therefore the invention taken as a whole is prima facie obvious.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Graham as applied to claims 21, 23, and 24 above, and further in view of Shen Yumei et al. (Foreign publication CN104292117A, Reference and English machine translation included with PTO-892, herein referred to as Yumei)
The disclosure of Graham is discussed above. Graham does not disclose the specific fluorescent dye structures recited in present claim 25. However, Graham does disclose that a wide variety of fluorescent structures can be used. (p. 7 paragraph 78)
As discussed previously, Yumei discloses fluorescent dye conjugates which use the fluorescent structure
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which is a tautomer of the structure
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appearing in present claim 25. (e.g. p. 6 paragraph 554) Yumei also discloses other conjugates comprising a Cy5 moiety:
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. (p. 56 paragraph 465) It would have been obvious to one of ordinary skill in the art at the time of the invention to use one of these fluorescent moieties from Yumei in the structures described by Graham. One of ordinary skill in the art would have seen Graham’s disclosure of various classes of fluorescent structures as suggesting looking to the art for any known fluorescent structures used for the same purpose as conjugated fluorescent labels.
Therefore the invention taken as a whole is prima facie obvious.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Graham as applied to claims 21, 23, and 24 above, and further in view of Cavalli et al. (NPL reference 4 cited in 8/11/2023 PTO-1449)
The disclosure of Graham is discussed above. Graham does not disclose the specific fluorescent dye structures recited in present claim 25. However, Graham does disclose that a wide variety of fluorescent structures can be used, including cyanines. (p. 7 paragraph 78)
Cavalli discloses an activity-based probe for autotaxin wherein the detectable fluorescent label is Cy5. (p. 2312 scheme 1) It would have been obvious to one of ordinary skill in the art at the time of the invention to use Cy5 as the fluorescent moiety in the probes described by Graham. One of ordinary skill in the art would have seen the disclosure of Cavalli et al. as indicating that Cy5 was usable for the same purpose as a fluorescent label, and therefore would have seen the two structures as interchangeable.
Therefore the invention taken as a whole is prima facie obvious.
Conclusion
Claims 1, 5, 11, 17, 19-21, and 23-25 are rejected. Claims 2-4, 8-10, 12-13, 15-16, and 22 are objected to for depending from a rejected base claim but would be allowable if rewritten in independent form incorporating all the limitations of the rejected base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 5/8/2026
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