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 .
Sequence Compliance
Claim 13 contains 6 sequences that have 4 or more fully defined amino acids, which are designated SEQ ID NO: 1-6 in the sequence listing. These peptides must also have the sequence numbers in the claims, in accordance with WIPO ST.26, paragraph 3(k), provides that “specifically defined” means any nucleotide other than those represented by any amino acid other than those represented by the symbol “X.” Additionally, 37 CFR 1.831(c) requires that each nucleotide and/or amino acid sequence set forth in a "Sequence Listing XML" in accordance with 37 CFR § 1.831(a) must be referenced by a sequence identifier as defined in 37 CFR 1.832(a), preceded by the notation "SEQ ID NO:" or the like, when the sequence appears in the description or claims (see MPEP § 2412.05(a)).
As such, the claim 13 must contain SEQ NOs: 1-6, identifying each peptide linker with a distinct sequence. Additionally, the specification must be amended to incorporate these identifiers throughout. For example, at page 5, 16 and 17, FIG. 8, etc.
Note that the examiner called applicants on 05/21/26 to resolve these sequence issues and request an Examiner’s Amendment and Terminal Disclaimer to place this case in condition for allowance.
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.
Claim 26 is 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.
Regarding claim 26, the phrase “e.g.,” (for example) renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 1-6 and 8-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,396,649. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1 teaches “a method for the conjugation of a peptide linker comprising a lysine and/or a glutamine residue to an antibody, or an antigen-binding fragment thereof, using a microbial transglutaminase (MTG), the method comprising: a) mixing the antibody, or the antigen-binding fragment thereof, the peptide linker and the MTG within a fluid under determined conditions, thereby conjugating the peptide linker to the antibody, or the antigen-binding fragment thereof, under the catalyzing effect of the MTG; and b) extracting the conjugate obtained in step (a) from the fluid.” This meets the limitations of instant claim 1, except that the instant claims are drawn to .5x TO 50x molar ratio of linker to antibody or antigen-binding fragments. Similarly, claims 2 teaches a concentration of .01mg to 10mg/ml of MTG in the solution. However, it would have been obvious to one of ordinary skill in the art to have optimized the amounts of linker and antibody/antigen-binding fragments and the concentration of MTG through routine experimentation.
The MPEP 2144.06 states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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 Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.” Here, the amount of linker, antibody/antigen binding fragment and MTG in the liquid for the method of conjugation are obvious to optimize based on the ‘649 teaching of the same components in the same method of conjugation with the same materials.
As to the limitations of instant claim 3, the same method is taught by the claims of ‘649, which would thus inherently produce the same conjugation efficiency. Here, the same steps are performed with the same components, and would be expected to achieve the same efficacy.
Claim 4 is met because claim 7 of ‘649 teaches linkers having peptides comprising a lysine. Instant claims 5 and 6 are met because claims 10 and 11 teach an aqueous buffer solution comprising NaCl and Tris. Instant claims 8 and 9 are met by claims 2 and 3, which teach the same immunoglobulin antibodies and Fab antigen binding fragments. Instant claim 10 is met by claim 4, which teaches that same method of conjugating and with the same endogenous glutamine or lysine and artificial or genetic induction into the antibody/antigen fragment. Instant claim 11 is met by claim 5 of ‘649 teaching peptide linker comprising a fluorescent dye/label, a cell-cytotoxic or influencing moiety, a metal-chelator a functional peptide, a chemical moiety and/or a spacer moiety with Cn >20. Instant claim 12 is met by claim 6 of ‘649 teaching an enzymatically cleavable peptide sequence. Instant claims 13 is met by claim 13 teaching the same linker sequences. Instant claim 14 is met by claim 8 teaching a self-immolative group. Instant claim 15 is met because claim 9 teaches PAB as the self-immolative group. Instant claim 16 is met by claim 12 of ‘649 that the antibody is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human antibody or a bispecific antibody, and/or wherein the antibody is deglycosylated or non-glycosylated containing a mutation at residue N297 in the EU numbering scheme. Instant claim 17 is met by claim 13 of ‘549, which teaches that the attached cell-cytotoxic or influencing moiety is a toxin or an immune cell immunomodulatory/stimulating compound; and/or wherein the metal-chelator is suitable for SPECT/PET or MRI; and/or wherein the chemical moiety comprises a reactive group suitable for a click reaction; and/or wherein the spacer moiety comprises an alkyl or heteroalkyl chain, or a derivative thereof, or a poly ethylene glycol moiety. Claim 18 is met because claim 13 teaches that the toxin is MMAE; and/or wherein the reactive group suitable for a click reaction comprises an azide moiety, a cyclooctyne moiety, a tertrazine moiety, a trans-cyclooctene moiety, or a derivative thereof. Claim 19 is met by claim 15, teaching that the fluid comprises up to 60% of glycerol and/or an organic solvent. Claim 20 is met by claim 16 of ‘649, which teaches that the lysine peptide has a size of (C+N)n>20 and said glutamine peptide has a size of 1<(C+N)n<200. Instant claims 21-23 are met by claims 17-19 of ‘649, which teach the MTG conjugated to a polymer on a microbeads, where the microbeads are glass, nickel, polyethylene, polypropylene, poly(4-methulbutene), polystyrene, polyacrylate, polyethylene terephthalate, rayon, nylon, poly(vinyl butyrate), polyvinylidene difluoride (PCDF), silicones, polyformaldehyde, cellulose, cellulose acetate, nitrocellulose, gelatin, polysaccharides, polycaprolactone (PCL), polyacrylamide, polyacrolein, polydimethylsiloxane, polyvinyl alcohol, polymethylacrylate, perfluorocarbon, inorganic compounds, or copolymers consisting of any combination of two or more naturally occurring polymers, synthetic polymers or inorganic compounds and/or wherein the size of the microbead varies from 1 nm to 1000 μm. Claim 20 of ‘649 teaches that the polysaccharide may be agarose, alginate, carrageenan, chitin, dextran or starch; and/or wherein the inorganic compound is silica, glass, kieselguhr, alumina, gold, iron oxide, graphene, graphene dioxide or another metal oxide, meeting instant claim 24. Instant claims 25 and 26 are met by claim 21 and 22 of ‘649, which teach the same polymers and linkers between the MTG and polymer. Instant claim 27 is met because claim 23 of ‘649 teaches that the MTG polymer conjugate is retained in an active flow reactor.
Claims 1-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 11,396,649 in view of Protocols Online (hereinafter ‘Protocols’ TBS, 2012; https://www.protocolsonline.com/recipes/buffers/tris-buffered-saline-tbs/).
The difference between the ‘649 claims and the instant claims is that the claims of ‘649 do not teach a pH of 7.6.
The teachings of ‘649 have been described supra.
Protocols teaches that TBS is a common Tris/NaCl buffer because it is similar to human or animal physiological conditions. This reference teaches that a common “standard” formulation for 1X TBS is considered to be a solution that contains 0.05 M Tris and 0.15 M sodium chloride, pH 7.6, at 25 °C (as evidenced by Protocols Online, p. 1).
It would have been obvious at the filing date of the invention to have optimized the solution to pH 7.6 because the pH value Tri/NaCl buffer is slightly alkaline. One would have been motivated to use NaCl and Tris buffer because they are taught by Protocols to be at pH of 7.6 at 25 °C, which is useful in physiological conditions. There is a reasonable expectation of success that the claimed method of conjugation can be achieved under physiological conditions at a slightly alkaline pH of 7.6.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654
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