DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 97-110 are pending. Claims 1-96 are canceled.
3. Claim 97-110 are under examination.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on 8/28/2024 has been considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO’s electronic filing system (see Section I.1 of the Legal Framework for EFS-Web or Patent Center (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via EFS-Web or Patent Center as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via EFS-Web or Patent Center as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
5. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). See the specification, page 11, lines 22-23, page 19, line 25, page 37, line 31 and page 80, line 34 and page 81, line 8 (sequence ERPLVGV)
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
6. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See Figs. 4-9.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
7. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, see pages 35-36, for example. 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 MPEP § 608.01.
Abstract
8. The abstract of the disclosure is objected to because a typographical error. The term “or” before “prostate cancer” in line 4 should be “of”.
Claim Objections
9. Claim 110 is objected to because it recites an amino acid sequences which is not identified by a sequence identifier (SEQ ID NO). In this office action, ERPLVGV is identified by the examiner as residues 339-345 of SEQ ID NO: 35.
Claim Rejections - 35 USC § 112
10. 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.
11. Claims 97-110 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.
Independent claim 97 recites a limitation "the one or more surrogate peptides comprise the amino acid sequence of SEQ ID NO:40 (P2) and/or SEQ ID NO:41 (P4)". With regard to the term “and”, the limitation can be interpreted as one peptide comprises both SEQ ID NO:40 and SEQ ID NO:41. It may also be interpreted as two peptides, one peptide comprises SEQ ID NO:40 and the other peptide comprises SEQ ID NO:41. Because it is unclear if one peptide comprising both SEQ ID NO: 40 and 41, or two separate peptides are being detected, the metes and bounds of the claimed invention is unclear and the claim is indefinite.
Claims 98-110 depend from claim 97 and are rejected for the same reasons.
Claim Rejections - 35 USC § 112
12. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
13. Claims 103, 108 and 110 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
The claims are rejected because the specification lacks adequate written description for a genus of proteins that specifically bind to the sequence of SEQ ID NO:35, and a genus of antibodies that bind to the epitope of ERPLVGV (which is amino acids 339-345 of SEQ ID NO:35).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor, 97 USPQ2d at 1875 (“[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims.”). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity.
Lastly, even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
Claims 103 and 108 recite “a protein that specifically binds to the sequence of SEQ ID NO: 35”. The claims encompass a genus of proteins solely defined by their binding antigen. The specification only discloses three antibodies that specifically bind to the sequence of SEQ ID NO: 35. The specification does not disclose any non-antibody proteins that can bind SEQ ID NO:35.
Claim 110 recites “wherein the antibody binds to an epitope comprising an amino acid sequence of ERPLVGV”. Claim 10 encompasses a genus of antibodies solely defined by their binding epitope. The specification discloses only one antibody, i.e. 6E3 which binds ERPLVGV sequence.
Therefore, the written description is not commensurate in scope with the claimed proteins and antibodies.
MPEP 2163 states “disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).
The interaction of the antibody binding domain with an antigen has been well characterized in the art. For example, Reis et al (Frontiers in Molecular Biosciences, 2022, 9: 945808) teaches that the paratope is the region of the Ab surface that is directly interacting with the corresponding antigen. It usually includes portions of both the light (L) and heavy (H) Ab chains. In particular, the paratope is often assumed to include all of the six CDRs, which are located in the variable domains VH and VL of the respective chains (see Figure 3A). The six CDRs are optimized by our immune system to generate high affinity paratopes for the molecular recognition of a specific target (page 5 under subheading 3.1). In the majority of paratopes (85%), we found the co-participation of framework (Fw) residues. This is an interesting aspect as their main role is to act as a scaffold for the CDRs. In fact, their contribution, while generally less important than that of the CDRs, can account for as much as 30% of the paratope (page 6, para 1). Reis et al. teaches that the epitope is the region of the Ag surface that is directly interacting with the Ab (see Figure 5A). The structural analysis of the antigens in our database shows that on average the epitope contains 14.6 ± 4.9 residues, thus it is similar in size to the paratope (page 7, column 2). Epitopes comprising only one linear amino acid sequence, often called sequential or linear epitopes, are rarely observed. Indeed, epitopes often are conformational, i.e., consisting of portions of the Ag that are discontinuous in sequence and become spatially close only upon folding (page 8, column 1). Abdiche et al. (PLOS ONE, 2017, 0169535) teaches antibodies targeting closely adjacent or minimally overlapping epitopes can displace one another (abstract). Abdiche et al. teaches that structural interpretation of these empiric cross-blocking results suggests that displacement occurs between mAbs that have minimal to no steric clashes or shared epitope contacts, reinforcing our proposed hypothesis of displacement occurring via a transient sandwich complex within which the mAbs kinetically perturb one another, resulting in the complex collapsing by expelling one mAb and retaining the other (page 14). These findings show that antibodies do not need to bind to the same epitope as another antibody to compete with the antibody for binding.
As shown by these prior art, the interaction of the antibody binding domain with antigen and identifying potential epitopes on proteins have been well characterized. However, the prior art does not teach how to predict the structural features of the antibodies that bind to a disclosed epitope. Thus, one still cannot predict the structural or functional features of plethora of antibodies that bind to a disclosed antigen or epitope, or compete with another antibody for binding to an epitope. These and other studies on antibody epitopes do not provide sufficient information for a skill artisan to predict the structural and functional properties of a genus of antibodies that bind to a particular antigen or epitope based on the disclosure of an antibody epitope or species of antibodies that bind to a particular epitope.
The specification discloses three antibodies 2C12, 3F4 and 6E3 which can bind SEQ ID NO:35. Among them, only one antibody 6E3 can bind ERPLVGV sequence. From the specification's disclosure, there is no basis by which the artisan would expect that antibodies 2C12, 3F4 and 6E3 are representative number of species for the genus of antibodies that bind SEQ ID NO:35, much less proteins that bind SEQ ID NO: 35, and the antibody 6E3 is representative number of species for the genus of antibodies that bind ERPLVGV sequence. Neither do the disclosed antibody provides a structure that would be expected to be common to the members of the genus.
Without further testing, one cannot envision the structures of all proteins that can bind SEQ ID NO:35, and all antibodies which can bind the ERPLVGV sequence. The specification does not purport to describe any correlation between a particular protein or antibody structure and the claimed binding function. Accordingly, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
It is noted that, “[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Claim Rejections - 35 USC § 102
14. 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.
15. Claims 97-98 and 100 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pierce et al. (WO2013019634A1, pub. date: 2/7/2013, IDS filed on 8/28/2024).
Regarding claims 97, 100, Pierce et al. teaches a method comprising detecting FLNA peptide #43 (AGVAPLQVK, the instant SEQ ID NO:40) and FLNA peptide #54 (YNEQHVPGSPFTAR, the instant SEQ ID NO:41) by nano-ESI-RPLC-MSMS in trypsin digested samples of human patients having breast cancer (Fig. 15(c), Fig. 16(u) and 16(v), p50, para 2).
Regarding claim 98, Pierce teaches that the sample is serum (page 44, lines 10-11 and page 50).
16. Claims 97, 100-101 and 105 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Grote et al. (WO2016/196522A1, pub. date: 12/8/2016, filing date: 5/31/2016, effectively filed date: 5/29/2015, IDS filed on 8/28/2024).
Regarding claims 97, 100-101, Grote et al. teaches a method of detecting and quantifying a signature peptide, including FLNA peptides AGVAPLQVK (SEQ ID NO:243, which is 100% identical to instant SEQ ID NO:40) and YNEQHVPGSPFTAR (SEQ ID NO:225, which is 100% identical to instant SEQ ID NO:41) (page 107), in a trypsin digested sample by SRM mass spectrometry (MS) (Example 2, page 102, Fig. 4, claim 22). Grote et al. teaches that SRM is also known as MRM ([0091]).
Regarding claim 105, Grote et al. teaches that the sample was spiked with an internal standard peptide (Fig. 4 and claims 21-22), and the internal standard peptide is a synthetic stable isotope labeled version of a target signature peptide and is added in known amount to serve as an internal standard quantification ([0235]).
Claim Rejections - 35 USC § 103
17. 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.
18. Claims 97, 99, 100-103, 105 and 107-109 are rejected under 35 U.S.C. 103 as being unpatentable over Grote et al. (WO2016/196522A1, pub. date: 12/8/2016, filing date: 5/31/2016, effectively filed date: 5/29/2015, IDS filed on 8/28/2024), in view of Lin et al. (J Proteome Res., 2013, 12:5996-6003, IDS filed on 8/28/2024), and Castoria et al. (PLoS ONE, 2011, 6(2): e17218).
The teaching of Grote have been set forth above as they apply to claims 97, 100-101 and 105.
Regarding claims 102 and 107, Grote et al. teaches their method of quantifying a polypeptide in a sample comprising using an antibody with SISCAPA (Stable Isotope Standards and Capture by Anti-Peptide Antibodies). SISCAPA applies existing mass spectrometry quantitation methods (e.g., MRM) to the measurement of signature peptides of protein biomarkers. It improves sensitivity by capture of these signature peptides on immobilized anti-peptide antibodies ([0232]). Grote et al. teaches the sample is less complex after immunoprecipitation (page 35, line 5 from the bottom).
Grote does not specifically mention immunoprecipitation MRM.
Regarding claims 99, Grote does not teach detecting FLNA in the sample of a subject having or being suspected of having prostate cancer.
Lin et al. teaches detecting biomarkers in plasma sample by combining protein immunoprecipitation with MRM (IP-MRM) (abstract). Lin et al. teaches that IP-MRM with high-quality capture antibodies provides an effective alternative method to ELISA for protein quantitation in biological fluids (abstract). Lin et al. teaches that a key advantage of IP-MRM is the ability of the assay platform to perform multiplexed protein capture especially when amounts of plasma or serum samples are limited (page 6001, column 2, para 2).
Castoria et al. teaches immunoprecipitation of FLNA using a rabbit polyclonal antibody that binds specifically to FLNA (page 14, column 1). Castoria teaches that FLNA and its proteolytic fragments directly interact with AR, thereby modulating nuclear translocation and transcriptional action of AR as well as androgen dependence of prostate cancer LNCaP cells. Further, cytoplasmic localization of FLNA has been correlated with metastatic and hormone-refractory phenotypes in human prostate cancer, suggesting that intracellular localization of FLNA orchestrates invasiveness and even hormone responsiveness of prostate cancers [12].
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Grote to use IP-MRM MS to detect the FLNA peptides in view of Lin. One would have been motivated to do so because Grote et al. teaches the sample is less complex after immunoprecipitation (page 35, line 5 from the bottom), and Lin et al. teaches how to detect biomarkers in plasma sample by combining protein immunoprecipitation with MRM (IP-MRM) (abstract) and teaches that a key advantage of IP-MRM is the ability of the assay platform to perform multiplexed protein capture especially when amounts of plasma or serum samples are limited (page 6001, column 2, para 2). One would have had a reasonable expectation of success because Castoria et al. teaches immunoprecipitation of FLNA using a rabbit polyclonal antibody that binds specifically to FLNA (page 14, column 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have detected FLNA in the sample of a subject having or being suspected of having prostate cancer in view of Castoria. One would have been motivated to do so with a reasonable expectation of success because Castoria teaches that cytoplasmic localization of FLNA has been correlated with metastatic and hormone-refractory phenotypes in human prostate cancer.
Regarding claims 103 and 108-109, Grote et al. teaches that the signature peptide and internal standard were captured with an antibody that binds to the signature peptide (claim 22). MS signals of the signature peptide and internal standard were detected and quantified (claim 22). An antibody that binds to the signature peptide such as AGVAPLQVK (instant P2) or YNEQHVPGSPFTAR (instant P4) would bind to instant SEQ ID NO:35 because instant SEQ ID NO:35 comprises instant P2 and P4.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the antibody that binds AGVAPLQVK or YNEQHVPGSPFTAR for IP-MRM MS to capture and detect the FLNA peptides in view of Grote and Lin. One would have been motivated to do so with a reasonable expectation of success because Grote et al. teaches that the signature peptide and internal standard were captured with an antibody that binds to the signature peptide (claim 22), and Lin et al. teaches how to detect biomarkers in plasma sample by combining protein immunoprecipitation with MRM (IP-MRM) (abstract) and teaches that a key advantage of IP-MRM is the ability of the assay platform to perform multiplexed protein capture especially when amounts of plasma or serum samples are limited (page 6001, column 2, para 2).
19. Claims 97-98, 100-101 and 105 are rejected under 35 U.S.C. 103 as being unpatentable over Grote et al. (WO2016/196522A1, pub. date: 12/8/2016, filing date: 5/31/2016, effectively filed date: 5/29/2015, IDS filed on 8/28/2024), in view of Pierce et al. (WO2013019634A1, pub. date: 2/7/2013, IDS filed on 8/28/2024).
The teaching of Grote have been set forth above as they apply to claims 97, 100-101 and 105.
Regarding claim 98, Grote does not teach detecting FLNA peptides in serum.
Pierce et al. teaches a method comprising detecting FLNA peptide #43 (AGVAPLQVK, the instant SEQ ID NO:40) and FLNA peptide #54 (YNEQHVPGSPFTAR, the instant SEQ ID NO:41) by nano-ESI-RPLC-MSMS in trypsin digested sample of human patients having breast cancer (Fig. 15(c), Fig. 16(u) and 16(v), p50, para 2, wherein the sample is serum (page 44, lines 10-11 and page 50).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have detected FLNA peptides in serum in view of Pierce. One would have been motivated to do so with a reasonable expectation of success because Pierce teaches that FLNA peptides can be detected in serum.
20. Claims 97, 100-101 and 104-106.are rejected under 35 U.S.C. 103 as being unpatentable over Grote et al. (WO2016/196522A1, pub. date: 12/8/2016, filing date: 5/31/2016, effectively filed date: 5/29/2015, IDS filed on 8/28/2024), in view of van Platerink et al. (J Chromatography B, 2006, 830:151-157, IDS filed on 8/28/2024).
The teaching of Grote have been set forth above as they apply to claims 97, 100-101 and 105.
Regarding claims 104, Grote does not teach that the range of detection for P2 (SEQ ID NO:40) is 62.5 pg/ml to 1500pg/ml and for P4 (SEQ ID NO:41) is 563 pg/ml to 27000pg/ml.
Van Platerink shows that the detection limit of HPLC-MRM-MS for peptides in human plasma is 0.01 ng/ml and the quantification limit is between 0.05 and 0.2 ng/ml (abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the HPLC-MRM-MS of van Platerink to detect the FLNA peptides in view of van Platerink. One would have been motivated to do so with a reasonable expectation of success because van Platerink shows that the detection limit of HPLC-MRM-MS for peptides in human plasma is 0.01 ng/ml and the quantification limit is between 0.05 and 0.2 ng/ml (abstract).
Regarding claim 106, Grote does not teach that the one or more mass transitions m/z are selected from the group consisting of: 441.7 (M+2H)2+ [Wingdings font/0xE0]*84.5 (ys1+) for P2; 535 (M+3H)3+->832.4 (y81+) for P4, 445.5 (M+2H) 2+ [Wingdings font/0xE0]592.1 (ys1+) for P2 internal standard (P2_IS), and 538.4 (M+3H)3+->842.5(y81+) for P4 internal standard P4_IS.
However, the determination of useful transitions for the claimed peptides appears to fall within the scope of routine optimization. See MPEP 2144.05.
“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the recited transitions for detecting and quantitation of the FLNA peptides in view of Grote. One would have been motivated to do so because Grote teaches quantitating six transitions of each FLNA peptides using MRM MS and selecting the transition with the strongest peak area to represent the peptide ([0323] and [0336]). The same FLNA peptide would have generated same transitions including the recited ones. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected different transitions including those recited in the claims for the purpose of finding an optimum transition to detect the FLNA peptides.
Double Patenting
21. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
22. Claims 97-110 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,866,487B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
The claims of the patent disclose a method for detecting and/or quantifying the level of FLNA in a sample, comprising contacting the sample with an antibody construct, or antigen-binding fragment thereof, capable of binding filamin A (FLNA) under conditions such that the antibody construct or antigen-binding fragment thereof binds to FLNA in the sample, to thereby detect and/or quantify the level of FLNA in a sample,
wherein the method comprising detecting and/or quantifying one or more surrogate peptides in a protein digest prepared from said sample using mass spectrometry, wherein the mass spectrometry is multiple reaction monitoring (MRM) mass spectrometry,
wherein the MRM is immunoprecipitation-multiple reaction monitoring (IPMRM) comprising a FLNA immunoprecipitation step,
wherein the one or more surrogate peptides comprise the amino acid sequence of SEQ ID NO:40 (P2) and/or SEQ ID NO:41 (P4),
wherein the range of detection for P2 is 62.5 pg/mL to 1500 pg/mL and the range of detection for P4 is 563 pg/mL to 27000 pg/mL,
wherein a P2 internal standard (P2_IS) and/or a P4 internal standard (P4_IS) is also detected,
wherein the MRM comprises monitoring one or more mass transitions m/z selected from the group consisting of: 441.7 (M+2H)2+ [Wingdings font/0xE0]584.5 (Y5 1+) for P2, 535(M+3H)3+[Wingdings font/0xE0]832.4 (Y8 1+ ) for P4, 445.5 (M+2H)2+[Wingdings font/0xE0]592.1 (Y5 1+) for P2 internal standard (P2_IS), and 538.4 (M+3H)3+[Wingdings font/0xE0]842.5 (Y8 1+ ) for P4 internal standard P4_IS,
wherein the antibody comprises a heavy chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 21, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 20, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 19, and a light chain variable region comprising a CDR3 domain comprising the amino acid sequence set forth in SEQ ID NO: 24, a CDR2 domain comprising the amino acid sequence set forth in SEQ ID NO: 23, and a CDR1 domain comprising the amino acid sequence set forth in SEQ ID NO: 22. This antibody binds to epitope ERPLVGV, as evidenced by the instant specification (page 80).
Conclusion
23. No claims are allowed.
24. Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG SANG whose telephone number is (571)272-8145. The examiner can normally be reached Monday-Friday 8am-5pm.
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/HONG SANG/Primary Examiner, Art Unit 1646
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