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
Election/Restrictions
Applicant's election with traverse of Species (Group C - claims 21 & 23 and Group D - claim 9) in the reply filed on 7/6/26 is acknowledged. The traversal is on the ground(s) that groups A, B, and C merely recite alternative preparation techniques that are used within the same overall assay methodology. That is, each species operates within the same inventive concept, preparation of a protein sample followed by hydrolysis and analysis to obtain information regarding the protein. The claimed denaturation conditions, acidic/chaotropic hydrolysis conditions, and protease-treatment conditions represent alternative embodiments of the same process.
Additionally, Applicant contends that groups D and E represent optimization or variation of operating parameters within the same digestion-buffer preparation process. And the Office Action does not explain why searching all the claims would require a materially different field of search or different prior art. To the contrary, both claims arise from the same technological subject matter and would reasonably be expected to involve substantially overlapping prior art.
This argument was carefully considered but is not found persuasive because the claimed species are not obvious variants of each other. And the generic claims recite or encompass such a multiplicity of species that an unduly extensive and burdensome search would be necessary to search the entire scope of the claim. See MPEP § 803.02 and § 809.02(a).
Additionally, Applicant’s argument is not found persuasive because the Restriction Requirement dated 5/4/26 has established proper restriction according to MPEP§821.04(a) and MPEP§806.05(h). Although the species may have overlapped subject matter or are alternative embodiments they are not totally inclusive of all the species.
Each of the Species’ inventions require separate search and considerations of the prior art. The search required for each Species invention - is not totally encompassing of each other. Therefore, there is a burden to search all the inventions together. Due to the divergent subject matter the species are deemed a search burden.
Restriction is only proper when there would be a serious burden as evidenced by separate classification, status, or field of search even though the claims include independent or distinct inventions (MPEP 808.02).
Applicant has requested reconsideration at the proper time in accordance with the rejoinder provisions of the MPEP. Examiner acknowledges the provision and will reconsider rejoinder at the proper time.
2. The requirement is still deemed proper and is therefore made FINAL.
3. Claims 2, 3, 14, 16, 39-42, and 44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/6/26. Currently claims 1, 5, 8, 9, 11, 12, 21, 23, 24, 25, 27, 29, and 30 are under consideration.
Priority
4. The instant application has a priority date of January 28, 2020. This application claims benefit of U.S. Provisional Application Serial No. 62/966,731 filed January 28, 2020.
Information Disclosure Statement
5. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other
Information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the examiner on form PTO-892 or applicant on form PTO-1449 lists the references, they have not been considered. See references listed throughout the disclosure.
6. The information disclosure statement filed 1/2/26 has been considered as to the merits prior to First Action on the Merits.
Specification
7. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See page 40 and 42. MPEP § 608.01.
Abstract
8. This application does not contain an abstract of the disclosure as required by 37 CFR 1.72(b). An abstract on a separate sheet is required.
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.
9. Claims 11 and dependent claim 12 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.
A. Regarding claim 11, the phrase "optionally" renders the claim(s) indefinite because the claim(s) include(s) elements which may not be intended in the claim limitation. Will the follow up required by the claim or not, thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d).
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.
10. Claim(s) 1, 5, 11, 21, 23, 24, 25, 27, 29, and 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hunt (US 2016/0349269) in view of Biswas et al. (Contrasting Effects of Guanidinium Chloride and Urea on the Activity and Unfolding of Lysozyme, ACS Omega. 25 October 2018, Vol. 3, No. 10; pages 14119-14126).
Hunt disclose, compositions, methods, systems, and apparatuses for rapid sequence analysis of proteins, including location of post-translational modifications and disulfide bonds. Limited digestion of fully denatured antibody occurs in seconds by flowing sample in 8 M urea at constant pressure through a micro column reactor containing immobilized aspergillopepsin I (SEQ ID NO:1), resulting in a product mixture containing 3-10 kDa peptides, which is then fractionated by capillary column chromatography and analyzed by both electron transfer dissociation (ETD) and collision activated dissociation mass spectrometry.
This method provides 95% sequence coverage of a mAb and detects numerous post-translational modifications. For disulfide bond location, native mAb is subjected to longer digestion times. Release of disulfide containing peptides from accessible regions of the folded protein occurs with short digestion times.
The identity of peptides connected by a disulfide bond is determined using ETD and ion-ion proton transfer chemistry. See abstract and Summary.
The invention provides advantages over the art, including easy, precise control of digestion time to generate desired fragment lengths that facilitate LC-MS based sample analysis. See Summary.
As per claim 1, Hunt discloses a method for characterizing a protein (a method for characterizing a protein molecule; paragraph [0007]; claim 1), said method comprising: disposing said protein in a digestion buffer (a method for characterizing a protein, said method comprising dissolving said protein in a digestion buffer, passing the digestion buffer comprising said protein through a reaction chamber comprising at least one hydrolyzing agent, wherein said protein contacts said hydrolyzing agent and is present in the chamber for a period of time t sufficient to produce protein fragments and digestion of said protein occurs in the chamber, wherein the passing of the digestion buffer comprising the protein through the chamber is done at an adjustable flow rate, and performing multi-segment liquid chromatography tandem mass spectrometry LC MS/MS to characterize the protein; paragraph [0011]; claim 1); disposing a hydrolyzing agent inhibitor in the digestion buffer (protein is exposed to the hydrolyzing agent under chaotropic conditions, chaotropic agent is guanidinium chloride, where guanidinium chloride is the hydrolyzing agent inhibitor, paragraphs [0121], [0170]); passing the digestion buffer comprising said protein and said hydrolyzing agent inhibitor through a reaction chamber comprising at least one hydrolyzing agent, wherein said protein contacts said hydrolyzing agent in the presence of said inhibitor (protein is exposed to the hydrolyzing agent in guanidinium chloride, which is the hydrolyzing agent inhibitor,
paragraphs [0121], [0170]) and is present in the chamber for a period of time t sufficient to produce protein fragments and provide digestion of said protein in the chamber, wherein the passing of the digestion buffer comprising the protein and the hydrolyzing agent inhibitor through the chamber is done at an adjustable flow rate; and performing multi-segment liquid chromatography tandem mass spectrometry LC MS/MS to characterize the protein (a method for characterizing a protein, said method comprising dissolving said protein in a digestion buffer, passing the digestion buffer comprising said protein through a reaction chamber comprising at least one hydrolyzing agent, wherein said protein contacts said hydrolyzing agent and is present in the chamber for a period of time t sufficient to produce protein fragments and digestion of said protein occurs in the chamber, wherein the passing of the digestion buffer comprising the protein through the chamber is done at an adjustable flow rate, and performing multi-segment liquid chromatography tandem mass spectrometry LC MS/MS to characterize the protein, protein is exposed to the hydrolyzing agent in guanidinium chloride, which is the hydrolyzing agent inhibitor, paragraphs [0011], [0121], [0170]; claim 1).
Hunt does not disclose a motivation to select guanidinium chloride from the list of other useful agents.
However, Biswas discloses the motivation to select guanidinium chloride from the list of other useful agents (guanidinium chloride GdmCl denatures lysozyme with the disulfide bonds intact in the protein, whereas urea denatures the protein only when the disulfide bonds are broken; abstract).
It would have been obvious to a person of ordinary skill in the art, before the filing date of the invention, to have modified the method, as previously disclosed by Hunt, in order to have provided for the motivation to select guanidinium chloride from the list of other useful agents, as previously disclosed by Biswas (Biswas; abstract), to produce the digested protein with intact disulfide bonds, or protein with limited digestion (Biswas; abstract) (Hunt; abstract), which would provide more reliable results in identification of the disulfide bonds in the protein compared to the methodology of adjustment of the digestion times of the protein (Hunt; abstract). Further, provided that Hunt and Biswas both disclose the methodology of identification of disulfide bonds in protein structure or active sites through denaturation (Hunt; abstract; paragraphs [0240]) (Biswas; abstract; page 14119, figure 1; page 14119, first column, first paragraph; page 14122, first column, first paragraph), the modification to Hunt method, of providing for the motivation to select guanidinium chloride from the list of other useful agents, would provide the benefit of producing the digested protein with intact disulfide bonds, or protein with limited digestion (Biswas; abstract) (Hunt; abstract), which would provide more reliable results in identification of the disulfide bonds in the protein compared to the methodology of adjustment of the digestion times of the protein (Hunt; abstract).
As per claim 5, Hunt and Biswas, Hunt further discloses wherein said protein is selected from the group consisting of an antibody, an antibody-like molecule, an antibody light chain, an antibody heavy chain, or biologically active fragments and homologs thereof (the protein is selected from the group consisting of an antibody, an antibody-like molecule, an antibody light chain, an antibody heavy chain, or biologically active fragments and homologs thereof; paragraph [0022]).
As per claim 11, Hunt discloses a hydrolyzing agent inhibitor; paragraphs 0121 and 0170.
As per claims 21, 23, and 24, Hunt discloses the immobilization of a proteases; paragraph 0019 and 0030.
As per claim 25, Hunt discloses t ranges from 0.25-20seconds; paragraph 0015-0017.
As per claim 27, Hunt discloses adjustable flow rates; paragraph 0020.
As per claim 29, Hunt fragment sizes ranging from 3KDa-10KDa mass; paragraph 0013.
As per claim 30, Hunt analyzes the protein fragments; paragraph 0007.
11. Claim(s) 8, 9, and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hunt (US 2016/0349269) in view of Biswas et al. (Contrasting Effects of Guanidinium Chloride and Urea on the Activity and Unfolding of Lysozyme, ACS Omega. 25 October 2018, Vol. 3, No. 10; pages 14119-14126) and further in view of Cao et al., (Characterization and analysis of scFv-lgG bispecific antibody size variants, MABS. 20 September 2018, Vol. 10, No.8; pages 1236-1247).
Please see Hunt (US 2016/0349269) in view of Biswas et al. (Contrasting Effects of Guanidinium Chloride and Urea on the Activity and Unfolding of Lysozyme, ACS Omega. 25 October 2018, Vol. 3, No. 10; pages 14119-14126)as set forth above.
Hunt (US 2016/0349269) in view of Biswas et al. (Contrasting Effects of Guanidinium Chloride and Urea on the Activity and Unfolding of Lysozyme, ACS Omega. 25 October 2018, Vol. 3, No. 10; pages 14119-14126) differ from the instant invention in not specifically teaching a bispecific antibody bsAb.
However, Cao discloses wherein said antibody is a bispecific antibody bsAb (bispecific antibodies comprise single-chain variable fragments scFv linked to different locations of an intact immunoglobulin with intrachain or intermolecular disulfide bonds formed by cysteines of scFv, intermolecular disulfide bonds lead to the formation of highly stable dimers and aggregates; abstract).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the invention, to have modified the method, as previously disclosed by Hunt in view of Biswas et at., in order to have provided for wherein said antibody is a bispecific antibody bsAb, as previously disclosed by Cao (Cao; abstract), to provide additional information on type of the antibodies that can be characterized by the method (Hunt; paragraphs [0011], [0022]; claim 1). Further, provided that Hunt, Biswas, and Cao disclose the methodology of characterization of antibody through digestion followed by analysis by mass-spectrometry (Hunt; abstract; paragraphs [0011], [0022]; claim 1) (Cao; abstract; page 1238, figure 3), the modification to Hunt method, of providing for wherein said antibody is a bispecific antibody bsAb, would provide the benefit of providing additional information on type of the antibodies that can be characterized by the method (Hunt; paragraphs [0011], [0022]; claim 1).
Absent evidence to the contrary to characterization of known antibody configuration in the methods disclosed in the prior art (Hunt in view of Biswas et al.) is deemed an obvious design choice demonstrated by the prior art.
KSR forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See recent Board decision Ex parte Smith,--USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007)(citing KSR, 82 USPQ2d at 1396).
As per claims 9 and 11, the optimization of the digest buffer concentration and the hydrogen agent inhibitor preference (protamine) are obvious. Absent criticality it is obvious to adjust concentrations and starting reagents in the assays disclosed by the prior art as a means of optimization.
12. For reasons aforementioned, no claims are allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LISA V COOK whose telephone number is (571)272-0816. The examiner works a flexible Part-Time schedule but can normally be reached on Monday, Thursday, and Friday from 9am to 5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached on 571-270-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Lisa V. Cook
Patent Examiner
Art Unit 1641
Hoteling
9/19/26
/LISA V COOK/Primary Examiner, Art Unit 1641
Prosecution Insights