DETAILED ACTION
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 .
Claims 1-20 are pending in the application. No Requirement for Restriction/Election has been mailed.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application claims the benefit of US Provisional Application No. 63/409,812 filed on 25 September 2022.
Claims 1-20 have an effective US filing date of 25 September 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7 April 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
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 1-20 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.
Claims 1, 3 and 13 are indefinite wherein they recite elements that are described by not what they are materially/structurally but by what they do. Claim 1 states “a high-affinity monomeric biotin-binding protein” and Claim 3 This is merely functional language and MPEP 2173.05(g) states that, without recitation of some structure, “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim’ and thus be indefinite. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971)”. Such is the case here where it is unclear what materials are encompassed by these terms of the claim. Since the independent claims are rejected, this affects the scope of all depending claims.
Claims 5-6, 8-9, 11-12, 15-16, 18, and 20 are rejected for recitation of an intended result/effect without conferring any structural/material difference on the elements of the parent claim, nor imposing a manipulative difference on the scope of the parent claim. These claims recite: a dissociation constant of the high-affinity monomeric biotin-binding protein; or, a biotin rate constant of dissociation (Koff). Since materials cannot be separated from their properties (MPEP 2144.09), these recitations do not further limit the materials recited in the parent claim. Additionally, these recitations render indefinite the scope of the claim because is unclear if assessing the dissociation constant or rate constant of dissociation is required for infringement since there are no positively stated active method steps for determining dissociation.
Claim Rejections - 35 USC § 103
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 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.
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.
Claim 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Guardigli et al., J Histochem and Cytochem, Vol. 53(12): 1451-1457, 2005 and Howarth et al., Nature Methods, 3(4): 267-273, 267-273, April 2006.
Regarding Claim 1, the Guardigli et al. prior art teaches reacting a tissue samples, specifically, tissue samples obtained by diagnostic liver needle-biopsy (pg. 1452, Samples), with a reagent containing a high-affinity biotin-binding protein, specifically, the HRP-streptavidin conjugate (pg. 1453, Reagents and Immunocytochemistry). The method of Guardigli reacts the tissue sample with a primary antibody to an analyte under investigation (anti-MRP monoclonal mouse antibody, see pg. 1453, Reagents). Then Guardigli et al. react the tissue sample with a secondary antibody containing biotin, specifically, a biotinylated species-specific secondary antibody (pg. 1453, Reagents and Immunocytochemistry). The method of Guardigli et al. react the tissue sample with a biotin-binding protein that is linked with an enzyme, namely the horse radish peroxidase conjugated streptavidin. Lastly, the prior art teaches ; and - reacting the tissue sample with a substrate/chromogen reagent to the enzyme; namely, the prior art teaches colorimetric detection of bound HRP using the HRP chromogen 3,3’-diaminobenzidine (pg. 1453, Colorimetric Detection).
Regarding claim 2, the method of Guardigli et al. teach a peroxidase enzyme, namely, horst radish peroxidase (HRP) (pg. 1453, Colorimetric Detection).
Regarding claim 3, the method of Guardigli et al. prior art teaches the tissue sample is reacted with the reagent containing a high-affinity biotin-binding protein (HRP-streptavidin conjugate) and with a peroxidase-blocking reagent wherein it teaches “Endogenous peroxidase
activity was blocked using 0.3% H2O2 in methanol for 30 min (pg. 1453, Immunohistochemistry).
While Guardigli et al. prior art teaches is a high-affinity biotin-binding protein, specifically HRP-streptavidin, it does not teach monomeric biotin-binding protein of instant claim 1 or the monovalent avidin of instant claim 4 and instant claim 7. The Howarth et al. prior art, however, remedies this deficiency by teaching the development of monomeric/monovalent streptavidin variants (Abstract).
A person having ordinary skill in the art, before the effective filing date of the application, to substitute the monovalent streptavidin, as taught by Howarth, in the method of Guardigli et al. Motivation to do so is explicit within the Howarth reference wherein it teaches “multimerization can interfere with normal biomolecule function or trafficking, or complicate affinity measurements, limiting the applications of this system” (pg. 1, first paragraph) whereas a monovalent streptavidin has a single femtomolar biotin binding site, and it can be applied to “cross-linking–free labeling of biotinylated cell-surface proteins” on the surface of living neurons (pg. 2, first full paragraph). Given the guidance in the references, a person having ordinary skill would have been able to make this substitution with predictable success. In KSR International Co. v. Teleflex, Inc., the Supreme Court has stated that combining prior art elements according to known method to yield predictable results is prima facie obvious if the following rationale can be applied:
(1) the prior art includes each element claimed though not necessarily in the same reference.
(2) it was within the technical grasp of one of ordinary skill in the art to combine the elements as claimed by known methods, and that in combination, each element merely would have performed the same function as it did separately.
(3) one of ordinary skill in the art would have recognized that the results of such combination were predictable.
(KSR International Co. v. Teleflex, Inc. 127 S. Ct. 1727, 82 USPQ2d 1385, Supreme Court, April 30, 2007).
Regarding claims 5 and 6, since these claims only recite the properties (dissociated constant or dissociated rate) of the high-affinity monovalent avidin of claim 4, then the Howarth monovalent avidin inherently teaches these properties. Specifically, Howarth et al. teach: “We determined a Kd of 4.8 × 10−14 ± 0.5 × 10−14 M (s.e.m.) for monovalent A1D3” (pg. 3, third paragraph). The Howarth prior art goes on to say: “A1D3 also had a comparable off rate to wild-type streptavidin for [3H]biotin itself (Fig. 3d). The measured off rates were 5.2 × 10−5 ± 0.3 × 10−5 s−1 (s.e.m.) for wild-type streptavidin and 6.1 × 10−5 ± 0.2 × 10−5 s−1 (s.e.m.) for A1D” (pg. 3, fourth paragraph). Thus the monovalent avidin used in Howarth teaches a Kd of less than 10 nM as required by instant claim 5 and a Koff rate of less than 10 X 10-3 minutes-1, as required by instant claim 6.
Regarding claims 8 and 9, since these claims only recite the properties (dissociated constant or dissociated rate) of the high-affinity monovalent avidin of claim 7, then the Howarth monovalent avidin inherently teaches these properties. The monovalent avidin used in Howarth has a Kd of 4.8 × 10−14 M, which is less than 10 nM as required by instant claim 8. The monovalent avidin used in Howarth has a Koff rate of 6.1 × 10−5 10−5 s−1, which is less than 10 X 10-3 minutes-1, as required by instant claim 9.
Regarding claim 10, the monovalent avidin taught by Howarth et al. is an “avidin family high-affinity monovalent biotin-binding protein”.
Regarding claims 11 and 12, since these claims only recite the properties (dissociated constant or dissociated rate) of the high-affinity monovalent avidin of claim 7, then the Howarth monovalent avidin inherently teaches these properties. The monovalent avidin used in Howarth has a Kd of 4.8 × 10−14 M, which is less than 10 nM as required by instant claim 11. The monovalent avidin used in Howarth has a Koff rate of 6.1 × 10−5 10−5 s−1, which is less than 10 X 10-3 minutes-1, as required by instant claim 12.
Regarding claims 13-20, the Guardigli et al. prior art reference teaches a biotin blocking method comprising the steps of: reacting a liver tissue sample (pg. 1452, Samples) simultaneously with a reagent containing a high-affinity biotin-binding protein and with a primary antibody to an analyte under investigation, specifically, the HRP-streptavidin conjugate (pg. 1453, Reagents and Immunocytochemistry) and a primary antibody to an analyte under investigation (anti-MRP monoclonal mouse antibody, see pg. 1453, Reagents). The method of Guardigli et al. further requires reacting the tissue sample with a secondary antibody containing biotin - a biotinylated species-specific secondary antibody (pg. 1453, Reagents and Immunocytochemistry). Lastly the prior art reference teaches reacting the tissue sample with a substrate/chromogen reagent to the enzyme namely, the prior art teaches colorimetric detection of bound HRP using the HRP chromogen 3,3’-diaminobenzidine (pg. 1453, Colorimetric Detection).
While Guardigli teach a high-affinity biotin-binding protein it does not teach the monomeric high-affinity biotin-binding protein of instant claims 13-20. As stated above, the Howarth et al. prior art remedies this deficiency by teaching the development of monomeric/monovalent streptavidin variants (Abstract). Since claims 15-16 and 18-20 only recite properties (dissociated constant or dissociated rate) of the high-affinity monovalent avidin of claim 13, then the Howarth monovalent avidin inherently teaches these properties. The monovalent avidin used in Howarth has a Kd of 4.8 × 10−14 M, which is less than 10 nM as required by instant claims 15 and 18. The monovalent avidin used in Howarth has a Koff rate of 6.1 × 10−5 10−5 s−1, which is less than 10 X 10-3 minutes-1, as required by instant claims 16 and 20. The monovalent avidin taught by Howarth et al. is an “avidin family high-affinity monovalent biotin-binding protein”, as required by claim 19.
A person having ordinary skill in the art, before the effective filing date of the application, could have substituted the monovalent streptavidin, as taught by Howarth, in the method of Guardigli et al. Motivation to do so is explicit within the Howarth reference wherein it teaches “multimerization can interfere with normal biomolecule function or trafficking, or complicate affinity measurements, limiting the applications of this system” (pg. 1, first paragraph) whereas a monovalent streptavidin has a single femtomolar biotin binding site, and it can be applied to “cross-linking–free labeling of biotinylated cell-surface proteins” on the surface of living cells (pg. 2, first full paragraph). Given the guidance in the references, a person having ordinary skill would have been able to make this substitution with predictable success. In KSR International Co. v. Teleflex, Inc., the Supreme Court has stated that combining prior art elements according to known method to yield predictable results is prima facie obvious if the following rationale can be applied:
(1) the prior art includes each element claimed though not necessarily in the same reference.
(2) it was within the technical grasp of one of ordinary skill in the art to combine the elements as claimed by known methods, and that in combination, each element merely would have performed the same function as it did separately.
(3) one of ordinary skill in the art would have recognized that the results of such combination were predictable.
(KSR International Co. v. Teleflex, Inc. 127 S. Ct. 1727, 82 USPQ2d 1385, Supreme Court, April 30, 2007).
Thus, the invention of the claims is obvious in view of what was known in the prior art regarding monovalent avidin mutants and combining known elements according to known methods. Claims 1-20 are rejected under 35 U.S.C. 103.
Conclusion
No claim is allowed.
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/STACEY N MACFARLANE/Examiner, Art Unit 1675