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 .
Advisory Comment
The incorporation by reference statement of the sequence listing states the file size in KB instead of bytes and the date last modified instead of the date created. Appropriate action in reply to this action is required for sequence compliance. Otherwise, the response to the action will be considered nonresponsive.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. BE2021/5141, filed on 02/26/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/25/2023 and 02/23/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure is being considered by the examiner.
Claim Rejections - 35 USC § 112(b)
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 1-9, 12 and 22 are rejected as indefinite for plurality of peptide epitopes grafted to SEQ ID NO: 1 could be interpreted in two ways such that the metes and bounds of the claim are unclear. It could be interpreted that the plurality of peptide epitopes grafted within the SEQ ID NO: 1 sequence or that the plurality of peptide epitopes are grafted to SEQ ID NO: 1 such that the peptides protrude out from SEQ ID NO: 1. For the purposes of examination, the latter interpretation will be used. Dependent claims 2-10 and 22 are included in this rejection because they do not resolve the indefiniteness recited in claim 1.
Claims 3 and 4 are rejected as indefinite because the claims recite exemplary language in parentheses: “mole peptide epitope: mole SEQ ID NO: 1”. In this case, the phrase provides exemplary structure that describes SEQ ID NO: 1 beyond what is recited by the rest of the claim. According to MPEP 2173.05(d), examples and preferences recited in the claim can lead to confusion over the intended scope of a claim. The metes and bounds of the claim are indefinite because it is unclear if the exemplary structure is a claim limitation.
Claim 16-19 and 23-24 are rejected as indefinite because without a conjunction (i.e. and) recited in claim 16, it is unclear whether all or some of the steps recited in the claims are necessary. Therefore, the metes and bounds of the claim are unclear. Dependent claims 17-19, and 23-24 are included in this rejection because they do not resolve the indefiniteness recited in claim 16. For the purposes of examination, the claim will be interpreted as: “A method of coupling…contacting said activated carrier… and separating the activating carrier…” (emphasis added).
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(s) 1-21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arumugham et al., 2012, US-8227403-B2 (hereafter Arumugham), as evidenced by Reusch, 2013, Peptides & Proteins, Michigan State University pgs. 1-14 ) (hereafter Reusch) (see instant PTO-892).
Regarding claims 1, 10, 13, 14, and 20, Arumugham teaches a composition comprising a CRM197 carrier protein, which is equivalent to instant SEQ ID NO: 1 (see below), to which a plurality (Column 36, lines 5-10) of peptide immunogens (i.e. fragments containing epitopes (Column, 17, lines 28- 35 and 59-64; Column 14 lines 66-67)) comprising a chain of at least 7 amino acids (Column 4, lines 50-54), have been covalently attached (Column 73, Claim 1) to the CRM197 carrier protein. The epitope comprising a chain of at least 7 amino acids that is attached to the CRM197 carrier protein of Arumugham are linked by peptide bonds, as evidenced by Reusch (pg. 2, first paragraph). Regarding Claim 2, Arumugham teaches that the plurality of epitopes are identical by demonstrating increased Aβ1-7 peptide load on the CRM197 carrier; it depicts that multiple of the Aβ1-7 peptides are conjugated to CRM197 (Fig. 4). Regarding claims 3-4, it teaches multiple antigenic peptide (MAP) conjugates, where 3 epitopes are conjugated to the carrier in tandem (Example 8, Table 8). Regarding claim 5, Arumugham teaches that the peptides reacted with the amine group of CRM197 (Fig., 1, and Example 1). Regarding Claim 6, Arumugham teaches a heterobifunctional crosslinking agent, namely bromoacetic acid N-hydroxysuccinimide ester, is used to attached peptide immunogens to the CRM197 carrier (Example 1). Regarding claims 7 and 14, Arumugham teaches the heterobifunctional crossing agent is reactive for an amine and sulfhydryl-reactive group (Column 24, lines 20-25). Regarding claims 8, 9, 14 Arumugham teaches that a cysteine can be added to the C- or N- terminus of the natural (Column 18, lines 44-46) peptide immunogens (Column 22, lines 18-26), which provides a sulfhydryl group on one end of the peptide for conjugation (Column 23, lines 25-30). Regarding Claims 10-11, Arumugham teaches a method of immunization by administering an Aβ/CRM conjugated peptide, as described above, to mice (Column 42, lines 63-67; Table 10); it also teaches administration to humans for treating a degenerative disease (Column 27, lines 20-25). Regarding Claims 12 and 15, it teaches that the composition further comprises an Al(OH)3 adjuvant (Table 10). Regarding Claim 13, it teaches an aqueous solution comprising the peptides or conjugates (Column 28, lines 20-23) and that buffers may be used to ensure a specified pH (Column 28, line 25-26). Claims 14 and 15 recite elements of a kit which are all described above.
Regarding Claim 16, Arumugham teaches (a) identifying Aβ peptides comprising at least 7 amino acids and an -SH group, (b) obtaining the CRM197 protein carrier, (c) activating the carrier with a heterobifunctional crosslinking agent, namely bromoacetic acid N-hydroxysuccinimide ester, which is reactive for an -NH2 and -SH group, (d) purifying the activated carrier protein to cause a plurality of -NH2 groups of SEQ ID NO: 1 to react with the heterobifunctional crosslinking agent (e) mixing Aβ peptides with activated carrier that is reactive for the -SH group of the peptides, and (f) purifying the peptide immunogen-carrier protein with dialysis (Fig. 1, Examples 1-3; Column 27, 14-20). Regarding Claim 17, it teaches that the free amino groups of CRM197, namely the 39 lysine residues, are reacted by adding an excess of the heterobifunctional crosslinking agent (Column 31, lines 5-20). Regarding Claims 18 and 19, Arumugham teaches dissolving peptide immunogen-carrier protein in an aqueous solution (Column 28, lines 20-23) comprising a buffer (Column 28, line 25-26) to ensure a specified pH and amino acid analysis (Example 2). Arumugham teaches lyophilization of an aqueous solution comprising the peptide immunogen-carrier protein (Column 28, lines 28-30).
Regarding claims 1 and 20, the compositions taught by Arumugham are pharmaceutical compositions (Column 28, lines 20-24; Column 28, lines 33-50). Regarding Claim 21 Arumugham teaches the composition further comprises an Al(OH)3 adjuvant (Table 10).
Instant SEQ ID NO: 1 identical to Arumugham SEQ ID NO: 40:
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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.
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Arumugham, as evidenced by Reusch, as applied to claim 1 above, and further in view of Crouzet et al., 2016 WO2016184963A1 (herafter Crouzet) (see instant PTO-892).
The teachings of Arumugham are described above.
However, Arumugham does not teach explicitly teach that the plurality of epitopes are hydrophobic.
Crouzet teaches a composition comprising an antigenic peptide, such as SEQ ID NO: 9 linked to a CRM197 protein carrier (pg. 47, lines 4-12) for treating an HIV-infected individual (abstract). According to the definition of hydrophobic in the instant specification (pg. 9, lines, 11-16), SEQ ID NO: 9 is hydrophobic. Crouzet teaches that administration of the composition comprising SEQ ID NO: 9 attached to a CRM197 carrier with a cross linker resulted in immune restoration in the responder group (Examples 2 and 3). Therefore, Crouzet teaches that hydrophobic peptide epitopes can be covalently attached to CRM197 successfully, and that these compositions can treat individuals with HIV.
It would have been obvious to one of ordinary skill in the art that the peptide epitopes in Arumugham’s composition could be changed, even to peptides that are hydrophobic, based on Couzet’s teachings. Since epitope sequences are specific to each target, one of ordinary skill in the art would be motivated to modify the peptide epitopes in Arumugham’s composition to make it effective for a wide variety of conditions. One of ordinary skill in the art would have had a reasonable expectation of success attaching a hydrophobic peptide epitope to the carrier based on Crouzet’s results, namely immune restoration to patients. Both sources are in the same field of endeavor, namely vaccine development.
Claim(s) 23-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Arumugham, as evidenced by Reusch, as applied to claim 16 above, and further in view of Heinrikson et al., Amino Acid Analysis by Reverse-Phase High Performance Liquid Chromatography: precolumn Derivatization with Phenylisothiocyanate, 1983, Analytical Biochemistry 1984 pgs. 65-74 (hereafter Heinrikson) (see instant PTO-892).
The teachings of Arumugham are described above.
Arumugham does not teach that the aqueous solution of Claim 18 comprises about 10-50 vol% of acetonitrile.
Heinrikson teaches amino acid analysis conducted with an aqueous solution comprising an ammonium acetate buffer used to ensure a specified pH and 50% acetonitrile by volume (Table 1).
Arumugham teaches amino acid analysis, but does not explicitly teach that this step comprises an aqueous solution comprising a buffer and about 10-50% acetonitrile. However, it would have been obvious to one of ordinary skill in the art to combine Arumugham’s teaching of an amino acid analysis step with Heinrickron’s protocol for amino acid analysis, which requires an aqueous solution comprising 50% acetonitrile and a buffer. One of ordinary skill in the art would have been motivated to implement Heinrickson’s protocol because Heinrickson teaches that this method is rapid, accurate, and allows for reproducible quantification of amino acids at picomole concentrations (pg. 72, right side, first paragraph). Furthermore, one of ordinary skill in the art would have a reasonable expectation of success because Heinrickson teaches this method is comparable in sensitivity and precision to other amino acid analysis methods (abstract).
Double Patenting
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 14-20 of copending Application No. 18/278,985 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other, as evidenced by Reusch and Blalock et al., WO-2007108808-A1 (hereafter Blalock).
Instant claims are recited above.
Copending claims 1-7, 18 recite pharmaceutical compositions comprising peptide epitopes SEQ ID NOs: 2, 3, 4 and/or 5; claims 2-7, and 18 specifically recite that the peptide epitopes are covalently coupled to one or more free -NH2 residues of SEQ ID NO: 1. Copending claims 8, 9, and 19 recite methods of using the composition of copending claim 1. Copending claims 14-17 and 20 recite a method of making the composition of copending claim 2.
The carriers recited in the composition claims of both applications are identical. The difference between the instant composition claims (1-9, 12-15 and 22) and the copending composition claims (1-7,18) is that the instant claims recite that the peptide epitopes comprise a chain of at least 7 amino acids and are hydrophobic, while the copending claims recite specific peptide epitope sequences, SEQ ID NOs: 2, 3, 4 and/or 5. The chain of amino acids in the copending application are linked by peptide bonds, as evidenced by Reusch (pg. 2, first paragraph). It would be obvious to one of ordinary skill in the art that the instant and copending claims are not patentably distinct because the peptide epitopes recited in the copending claims have at least 7 amino acids and according to the definition in the instant specification, at least SEQ ID NO: 3 is hydrophobic. In other words, it would be obvious to one of ordinary skill in the art that the instant composition claims, which recite any peptide epitope, encompass the more specific composition claims of the copending application.
The only differences between the instant method of use claims (10-11) and copending method of use claims (8, 9, 19) is that (a) the composition administered to a patient in the copending claims has specific peptide epitopes SEQ ID NOs: 2, 3, 4 and/or 5, which for the reasons discussed above is not a patentable distinction, (b) the recited disease is specifically myasthenia gravis. However, it would be obvious to one of ordinary skill in the art that these limitations are not patentably distinct because myasthenia gravis is an autoimmune disease as evidenced by Blalock (pg. 1, lines 10-15). Therefore, it would be obvious to one ordinary skill in the art the instant method of use claims encompass the more specific method of use claims in the copending application.
Lastly, the only difference between the instant method of production claims (Claims 14-19) and the copending method of production claims (14-17 and 20) is that steps in the copending method require peptide epitopes SEQ ID NOs: 3 or 5 while the instant claims broadly recite a peptide epitope comprising a free -SH group. However, SEQ ID NOs: 3 and 5 both have a cysteine end and therefore comprise a free -SH group. Therefore, it would be obvious to one of ordinary skill in the art that these claims are patentably indistinct.
Therefore, instant claims 1-22 are rejected as being unpatentable over the co-pending Application No. 18/278,985 claims 1-20. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
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/MICHELLE CALLAHAN BUCCINI/Examiner, Art Unit 1675
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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