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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 18, 2025 has been entered.
Status of the Claims
Claims 1-21 were originally filed March 25, 2021.
The preliminary amendment received March 25, 2021 amended claims 3-8, 10-12, 14-16, and 18-21.
The amendment received February 27, 2024 fails to show status identifiers and all of the amendments made. Claims 1 and 2 are amended as marked up. However, the claim set has deleted the amendments made in the preliminary amendment received March 25, 2021 without marking up the claims. Please review MPEP § 714 for how to properly amend the claims.
The amendment received September 13, 2024 amended claims 1, 2, 6, 11, and 13-15 and canceled claims 3, 5, 12, and 16-21. Please note: claims 4, 7, 8, and 10 were also amended without marking up the amendments in the claims. Applicants’ representative continues to make amendments without marking up the claims (see, at least, claims 1, 2, etc.; claim 1 “cysteine-linked” is now cysteine linked. “is described” was not shown to be deleted, etc.; claim 2 deleted “wherein the bottom segment”, etc.). Various claims did not mark up the dependency correctly (see claims 4, 6-8, 10, 11, and 13-15). Please review MPEP § 714 for how to properly amend the claims. If the next claim amendment is missing any mark ups, a request for information will be sent out and prosecution will be halted until the amendments are clearly marked. See MPEP § 704.11(b). The claim set received on February 27, 2024 should have been utilized to markup ALL claim amendments.
The amendment received March 24, 2025 amended claims 1, 4, 7, 8, 10, and 13-15 and canceled claims 2, 6, and 11.
Claims 1, 4, 7-10, and 13-15 are currently under consideration.
Claims 1, 7-9, 13, and 15 are currently under consideration.
Election/Restrictions
Applicants elected, with traverse, SEQ ID NOs: 4, 18, and 41 (please note: applicants should always refer to the SEQ ID NO: when discussing a specific sequence with a SEQ ID NO:) wherein SEQ ID NO: 18 is present at 0.1 to 2 parts per weight relative to 1 part by weight of SEQ ID NO: 4-SEQ ID NO: 41, HP-b-CD at 0.2 to 5 parts per weight relative to 1 part by weight of SEQ ID NO: 4-SEQ ID NO: 41, methionine at 0.01 to 1 parts per weight relative to 1 part by weight of SEQ ID NO: 4-SEQ ID NO: 41, tartaric acid at 0.01 to 1 parts per weight relative to 1 part by weight of SEQ ID NO: 4-SEQ ID NO: 41, and Montanide™ at 1 to 100 parts per weight relative to 1 part by weight of SEQ ID NO: 4-SEQ ID NO: 41 as the species in the reply filed on February 27, 2024. The traversal is on the grounds that Li et al. do not teach cyclodextrin and Barner et al. do not teach a lyophilized preparation comprising SEQ ID NOs: 3, 18, and 41 or SEQ ID NOs: 4, 18, and 41. This is not found persuasive because one cannot traverse Lack of Unity by attacking references individually where the Lack of Unity is based on the combination of references. In addition, please see the prior art of record below. The requirement is still deemed proper and is therefore made FINAL.
Claims 4, 10, 14, and 18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on February 27, 2024.
Priority
The present application is a 371 (National Stage) of PCT/JP2019/038223 filed September 27, 2019 which claims foreign priority to JP 2018-185532 filed September 28, 2018.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome any rejection of record because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Drawings
No Drawings are present.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3.
Withdrawn Objections
The objection to claim 1 regarding “3:” is duplicated in line 9 is withdrawn in view of the claim amendments received March 24, 2025 and entered with the RCE filed April 18, 2025.
The objection to claim 2 regarding “the top segment comprises SEQ ID NO: 4” should read “the bottom segment comprises SEQ ID NO: 4” is withdrawn in view of the cancellation of the claim in the claim amendment received March 24, 2025 and entered with the RCE filed April 18, 2025.
The objection to claim 2 regarding “the top segment comprises SEQ ID NO: 41” is missing from the claim is withdrawn in view of the cancellation of the claim in the claim amendment received March 24, 2025 and entered with the RCE filed April 18, 2025.
The objection to claim 6 regarding “wherein the cyclodextrin comprises at least selected from the group consisting of” should read “wherein the cyclodextrin is one or more selected from the group consisting of” is withdrawn in view of the cancellation of the claim in the claim amendment received March 24, 2025 and entered with the RCE filed April 18, 2025.
Maintained Objections
Claim Objections
Claim 1 is objected to because of the following informalities: an embedded period is present in line 13 (after “(SEQ ID NO: 18)”). Appropriate correction is required.
Arguments and Response
Applicants’ arguments directed to the objection for claim 1 were considered but are not persuasive for the following reasons.
Applicants contend that the amended claims address the objection.
Applicants’ arguments are not convincing since the embedded period is still present in the claim.
New Objections
Claim Objections
Claim 1 is objected to because of the following informalities: “cysteine linked” should read “a cysteine linked” (see line 4). Appropriate correction is required.
Claim 1 is objected to because of the following informalities: “SEQ ID NO” should read “SEQ ID NO:” (see line 5). Appropriate correction is required.
Claim 7 is objected to because of the following informalities: “according clam 1” should read “according to claim 1”. Appropriate correction is required.
Withdrawn Rejections
The rejection of claims 1, 2, 6-9, 11, 13, and 15 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 is withdrawn in view of the amendment received March 24, 2025 and entered with the RCE filed April 18, 2025.
The rejection of claims 1, 2, 6-9, 11, 13, and 15 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 is withdrawn in view of the amendment received March 24, 2025 and entered with the RCE filed April 18, 2025.
The rejection to claim 11 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of the cancellation of the claim in the amendment received March 24, 2025 and entered with the RCE filed April 18, 2025.
Maintained Rejections
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.
Claims 1, 7-9, 13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. U.S. Patent Application Publication 2015/0080321 published March 19, 2015; Tiwari et al., 2010, Cyclodextrins in delivery systems: Applications, J Pharm Bioallied Sci, 2(2): 72-79; and Mehmood et al., 2015, Excipients Use in Parenteral and Lyophilized Formulation Development, Open Science Journal of Pharmacy and Pharmacology, 3(3): 19-27.
For present claims 1, 7-9, 13, and 15, Li et al. teach SEQ ID NO: 3 (CMTWNQMNL) or SEQ ID NO: 4 (CYTWNQMNL) (i.e. same as present SEQ ID NOs: 3 and 4) linked via a disulfide bond between the N-terminal cysteines to CRMFPNAPYL/SEQ ID NO: 13 (i.e. present SEQ ID NO: 41) and SEQ ID NO: 244 (i.e. present SEQ ID NO: 18), tartaric acid at about 0.5 to about 2 equivalents, and adjuvants including Freund’s adjuvants (complete or incomplete) and Montanide™ in a 1:1 ratio (i.e. equal amount) (please refer to the entire specification particularly paragraphs 7, 32-37, 114, 115, 125, 129, 161-163, 172, 174; Examples; claims).
However, Li et al. do not teach cyclodextrin.
For present claims 1, 7-9, 13, and 15, Tiwari et al. teach that cyclodextrins including HP-b-CD/HP-bCD are well-known additives to peptide therapeutics to increase aqueous solubility, increase bioavailability, and increase stability (please refer to the entire reference particularly the abstract; “Advantages of Cyclodextrin Inclusion Complexation” section; “Peptide and protein delivery” subsection; “CD Applications in the Design of Some Novel Delivery Systems” section; “Cyclodextrin Effects on Important Drug Properties in Formulation” section).
However, Li et al. do not teach methionine or lyophilized formulations.
For present claims 1, 7-9, 13, and 15, Mehmood et al. teach lyophilized peptide formulations, methionine excipients, tartaric excipients, and cyclodextrin excipients (please refer to the entire reference particularly the abstract; sections 2, 4, and 5; Tables 3 and 7).
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." See 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.") and 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, 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); 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 (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.").
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions (i.e. excipients would stabilize the formulation; lyophilization would increase the shelf life of the formulation) and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of carrier/excipient) for another (i.e. species of HP-b-CD and methionine) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. lyophilization of peptide formulations to increase shelf-life; utilization and optimization of excipients to stabilize peptide formulations) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Li et al.; Tiwari et al.; and Mehmood et al. for claims 1, 7-9, 13, and 15 were considered but are not persuasive for the following reasons.
Applicants contend that the present claims are directed to solving a problem unique to cancer vaccines. Applicants contend that US Patent Application Publication 2021/0338587; paragraphs 179 and 184; and Examples 1, 5, 6, and 8 show that the concentration of cyclodextrin impacts the formulation. Applicants contend that the composition as claimed avoids the formation of insoluble components which is essential for a satisfactory injectable product. Applicants contend that there is nothing in the cited references that teach the components of present claims 8, 9, 13, or 15. Applicants contend that the specification teaches that succinic acid and g-CD or HP-b-CD shortens reconstitution time. Applicants also argue the references separately instead of the combination of the references.
Applicants’ arguments are not convincing since the teachings of Li et al.; Tiwari et al.; and Mehmood et al. render the lyophilized preparation of the instant claims prima facie obvious.
The present claims are drawn to the lyophilized preparation and not to a method of reconstituting the lyophilized preparation or a reconstituted preparation.
Paragraph 179 is directed to the results of one specific formulation with additional components not recited in the present claims and not the concentration ranges in the present claims (see the Table in paragraph 178). Paragraph 184 shows the results of specific formulations with additional components not recited in the present claims and not the concentration ranges in the present claims (see Table in paragraph 182). Examples 1, 5, 6, and 8 are not labeled as such in the originally filed specification (i.e. it is unclear which examples applicants’ representative is discussing). Therefore, the specific formulations with additional components and a single concentration of various components is not commensurate in scope with the present claims.
Please refer to the above rejections of record for the teachings of dependent claims 8, 9, 13, and 15.
Tiwari et al. (prior art of record) teach that cyclodextrins including HP-b-CD/HP-bCD are well-known additives to peptide therapeutics to increase aqueous solubility, increase bioavailability, and increase stability (please refer to the entire reference particularly the abstract; “Advantages of Cyclodextrin Inclusion Complexation” section; “Peptide and protein delivery” subsection; “CD Applications in the Design of Some Novel Delivery Systems” section; “Cyclodextrin Effects on Important Drug Properties in Formulation” section).
Please also refer to Serno et al. (provided with the Advisory Action) which teaches that cyclodextrins are known in the prior art to decrease aggregation and increase stability (please refer to the entire reference particularly the abstract; Introduction; Sections 2, 3 – particularly section 3.3, 4.2; Table 2).
Unexpected results must be commensurate in scope with the present claims. In addition, the addition of cyclodextrins to peptide therapeutics was known in the prior art to increase aqueous solubility, increase bioavailability, and increase stability (see Tiwari et al.).
The present examples all utilized formula 3 and very specific formulations (see paragraphs 182, 185, 188, 191, 194, 197, 200, and 208) which comprise components which are not part of the present claims.
It is respectfully noted that methionine is not required in present independent claim 1 or dependent claims 7, 8, 9, 13, and 15. Furthermore, two specific concentrations of methionine were utilized.
Mehmood et al. teach lyophilized peptide formulations, methionine excipients, tartaric excipients, and cyclodextrin excipients (please refer to the entire reference particularly the abstract; sections 2, 4, and 5; Tables 3 and 7).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions (i.e. excipients would stabilize the formulation; lyophilization would increase the shelf life of the formulation) and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of carrier/excipient) for another (i.e. species of HP-b-CD and methionine) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. lyophilization of peptide formulations to increase shelf-life; utilization and optimization of excipients to stabilize peptide formulations) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).
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, 7-9, 13, and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 9,181,302 in view of Li et al. U.S. Patent Application Publication 2015/0080321 published March 19, 2015; Tiwari et al., 2010, Cyclodextrins in delivery systems: Applications, J Pharm Bioallied Sci, 2(2): 72-79; and Mehmood et al., 2015, Excipients Use in Parenteral and Lyophilized Formulation Development, Open Science Journal of Pharmacy and Pharmacology, 3(3): 19-27.
U.S. Patent No. 9,181,302 claims CMTWNQMNL or CYTWNQMNL (i.e. present SEQ ID NOs: 3 and 4) linked via a disulfide bond between the N-terminal cysteines to CRMFPNAPYL (i.e. present SEQ ID NO: 41 – incorrectly identified as SEQ ID NO: 43 in the claims) and SEQ ID NO: 244 (i.e. present SEQ ID NO: 18).
Li et al. teach SEQ ID NO: 3 (CMTWNQMNL) or SEQ ID NO: 4 (CYTWNQMNL) (i.e. same as present SEQ ID NOs: 3 and 4) linked via a disulfide bond between the N-terminal cysteines to CRMFPNAPYL/SEQ ID NO: 13 (i.e. present SEQ ID NO: 41 – incorrectly identified as SEQ ID NO: 43 in the claims) and SEQ ID NO: 244 (i.e. present SEQ ID NO: 18), tartaric acid at about 0.5 to about 2 equivalents, and adjuvants including Freund’s adjuvants (complete or incomplete) and Montanide™ in a 1:1 ratio (i.e. equal amount) (please refer to the entire specification particularly paragraphs 7, 32-37, 114, 115, 125, 129, 161-163, 172, 174; Examples; claims).
Tiwari et al. teach that cyclodextrins including HP-b-CD/HP-bCD are well-known additives to peptide therapeutics to increase aqueous solubility, increase bioavailability, and increase stability (please refer to the entire reference particularly the abstract; “Advantages of Cyclodextrin Inclusion Complexation” section; “Peptide and protein delivery” subsection; “CD Applications in the Design of Some Novel Delivery Systems” section; “Cyclodextrin Effects on Important Drug Properties in Formulation” section).
Mehmood et al. teach lyophilized peptide formulations, methionine excipients, tartaric excipients, and cyclodextrin excipients (please refer to the entire reference particularly the abstract; sections 2, 4, and 5; Tables 3 and 7).
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." See 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.") and 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, 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); 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 (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.").
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions (i.e. excipients would stabilize the formulation; lyophilization would increase the shelf life of the formulation; adjuvants including Freund’s and Montanide™) and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of carrier/excipient) for another (i.e. species of tartaric acid, HP-b-CD, and methionine) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. lyophilization of peptide formulations to increase shelf-life; utilization and optimization of excipients to stabilize peptide formulations) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 9,181,302 in view of Li et al.; Tiwari et al.; and Mehmood et al. for claims 1, 7-9, 13, and 15 were considered but are not persuasive for the following reasons.
Applicants contend that none of the references recognize the problem with preparing cancer vaccines containing both a killer and a helper peptide and the problems encountered in making a successful product.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 9,181,302 in view of Li et al.; Tiwari et al.; and Mehmood et al. renders obvious the lyophilized composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The present claims are drawn to a lyophilized product and not a method of reconstitution and/or a reconstituted product.
The arguments of record above are incorporated in the entirety.
Claims 1, 7-9, 13, and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 9,248,173 in view of Li et al. U.S. Patent Application Publication 2015/0080321 published March 19, 2015; Tiwari et al., 2010, Cyclodextrins in delivery systems: Applications, J Pharm Bioallied Sci, 2(2): 72-79; and Mehmood et al., 2015, Excipients Use in Parenteral and Lyophilized Formulation Development, Open Science Journal of Pharmacy and Pharmacology, 3(3): 19-27.
U.S. Patent No. 9,248,173 claims CMTWNQMNL or CYTWNQMNL (i.e. present SEQ ID NOs: 3 and 4) linked via a disulfide bond between the N-terminal cysteines to CRMFPNAPYL (i.e. present SEQ ID NO: 41 – incorrectly identified as SEQ ID NO: 43 in the claims) and SEQ ID NO: 244 (i.e. present SEQ ID NO: 18).
Li et al. teach SEQ ID NO: 3 (CMTWNQMNL) or SEQ ID NO: 4 (CYTWNQMNL) (i.e. same as present SEQ ID NOs: 3 and 4) linked via a disulfide bond between the N-terminal cysteines to CRMFPNAPYL/SEQ ID NO: 13 (i.e. present SEQ ID NO: 41 – incorrectly identified as SEQ ID NO: 43 in the claims) and SEQ ID NO: 244 (i.e. present SEQ ID NO: 18), tartaric acid at about 0.5 to about 2 equivalents, and adjuvants including Freund’s adjuvants (complete or incomplete) and Montanide™ in a 1:1 ratio (i.e. equal amount) (please refer to the entire specification particularly paragraphs 7, 32-37, 114, 115, 125, 129, 161-163, 172, 174; Examples; claims).
Tiwari et al. teach that cyclodextrins including HP-b-CD/HP-bCD are well-known additives to peptide therapeutics to increase aqueous solubility, increase bioavailability, and increase stability (please refer to the entire reference particularly the abstract; “Advantages of Cyclodextrin Inclusion Complexation” section; “Peptide and protein delivery” subsection; “CD Applications in the Design of Some Novel Delivery Systems” section; “Cyclodextrin Effects on Important Drug Properties in Formulation” section).
Mehmood et al. teach lyophilized peptide formulations, methionine excipients, tartaric excipients, and cyclodextrin excipients (please refer to the entire reference particularly the abstract; sections 2, 4, and 5; Tables 3 and 7).
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." See 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.") and 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, 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); 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 (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.").
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions (i.e. excipients would stabilize the formulation; lyophilization would increase the shelf life of the formulation; adjuvants including Freund’s and Montanide™) and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of carrier/excipient) for another (i.e. species of tartaric acid, HP-b-CD, and methionine) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. lyophilization of peptide formulations to increase shelf-life; utilization and optimization of excipients to stabilize peptide formulations) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 9,248,173 in view of Li et al.; Tiwari et al.; and Mehmood et al. for claims 1, 7-9, 13, and 15 were considered but are not persuasive for the following reasons.
Applicants contend that none of the references recognize the problem with preparing cancer vaccines containing both a killer and a helper peptide and the problems encountered in making a successful product.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 9,248,173 in view of Li et al.; Tiwari et al.; and Mehmood et al. renders obvious the lyophilized composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The present claims are drawn to a lyophilized product and not a method of reconstitution and/or a reconstituted product.
The arguments of record above are incorporated in the entirety.
Claims 1, 2, 6-9, 11, 13, and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,759,509 in view of Li et al. U.S. Patent Application Publication 2015/0080321 published March 19, 2015; Tiwari et al., 2010, Cyclodextrins in delivery systems: Applications, J Pharm Bioallied Sci, 2(2): 72-79; and Mehmood et al., 2015, Excipients Use in Parenteral and Lyophilized Formulation Development, Open Science Journal of Pharmacy and Pharmacology, 3(3): 19-27.
U.S. Patent No. 11,759,509 claims CMTWNQMNL (SEQ ID NO: 3) or CYTWNQMNL (SEQ ID NO: 4) (i.e. present SEQ ID NOs: 3 and 4) linked via a disulfide bond between the N-terminal cysteines to CRMFPNAPYL (i.e. present SEQ ID NO: 41 – incorrectly identified as SEQ ID NO: 43 in the claims) and SEQ ID NO: 244 (i.e. present SEQ ID NO: 18).
Li et al. teach SEQ ID NO: 3 (CMTWNQMNL) or SEQ ID NO: 4 (CYTWNQMNL) (i.e. same as present SEQ ID NOs: 3 and 4) linked via a disulfide bond between the N-terminal cysteines to CRMFPNAPYL/SEQ ID NO: 13 (i.e. present SEQ ID NO: 41 – incorrectly identified as SEQ ID NO: 43 in the claims) and SEQ ID NO: 244 (i.e. present SEQ ID NO: 18), tartaric acid at about 0.5 to about 2 equivalents, and adjuvants including Freund’s adjuvants (complete or incomplete) and Montanide™ in a 1:1 ratio (i.e. equal amount) (please refer to the entire specification particularly paragraphs 7, 32-37, 114, 115, 125, 129, 161-163, 172, 174; Examples; claims).
Tiwari et al. teach that cyclodextrins including HP-b-CD/HP-bCD are well-known additives to peptide therapeutics to increase aqueous solubility, increase bioavailability, and increase stability (please refer to the entire reference particularly the abstract; “Advantages of Cyclodextrin Inclusion Complexation” section; “Peptide and protein delivery” subsection; “CD Applications in the Design of Some Novel Delivery Systems” section; “Cyclodextrin Effects on Important Drug Properties in Formulation” section).
Mehmood et al. teach lyophilized peptide formulations, methionine excipients, tartaric excipients, and cyclodextrin excipients (please refer to the entire reference particularly the abstract; sections 2, 4, and 5; Tables 3 and 7).
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." See 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.") and 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, 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); 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 (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.").
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions (i.e. excipients would stabilize the formulation; lyophilization would increase the shelf life of the formulation; adjuvants including Freund’s and Montanide™) and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of carrier/excipient) for another (i.e. species of tartaric acid, HP-b-CD, and methionine) would have yielded predictable results to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. lyophilization of peptide formulations to increase shelf-life; utilization and optimization of excipients to stabilize peptide formulations) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense”. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 11,759,509 in view of Li et al.; Tiwari et al.; and Mehmood et al. for claims 1, 2, 6-9, 11, 13, and 15 were considered but are not persuasive for the following reasons.
Applicants neglected to address the above rejection in the response received March 24, 2025.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 11,759,509 in view of Li et al.; Tiwari et al.; and Mehmood et al. renders obvious the lyophilized composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The arguments of record above are incorporated in the entirety.
Claims 1, 7-9, 13, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 17/434,231 in view of Li et al. U.S. Patent Application Publication 2015/0080321 published March 19, 2015; Tiwari et al., 2010, Cyclodextrins in delivery systems: Applications, J Pharm Bioallied Sci, 2(2): 72-79; and Mehmood et al., 2015, Excipients Use in Parenteral and Lyophilized Formulation Development, Open Science Journal of Pharmacy and Pharmacology, 3(3): 19-27.
Copending Application No. 17/434,231 claims CMTWNQMNL (SEQ ID NO: 3) or CYTWNQMNL (SEQ ID NO: 4) (i.e. present SEQ ID NOs: 3 and 4) linked via a disulfide bond between the N-terminal cysteines to CRMFPNAPYL (i.e. present SEQ ID NO: 41 – incorrectly identified as SEQ ID NO: 43 in the claims) and SEQ ID NO: 14 (i.e. present SEQ ID NO: 18).
Li et al. teach SEQ ID NO: 3 (CMTWNQMNL) or SEQ ID NO: 4 (CYTWNQMNL) (i.e. same as present SEQ ID NOs: 3 and 4) linked via a disulfide bond between the N-terminal cysteines to CRMFPNAPYL/SEQ ID NO: 13 (i.e. present SEQ ID NO: 41 – incorrectly identified as SEQ ID NO: 43 in the claims) and SEQ ID NO: 244 (i.e. present SEQ ID NO: 18), tartaric acid at about 0.5 to about 2 equivalents, and adjuvants including Freund’s adjuvants (complete or incomplete) and Montanide™ in a 1:1 ratio (i.e. equal amount) (please refer to the entire specification particularly paragraphs 7, 32-37, 114, 115, 125, 129, 161-163, 172, 174; Examples; claims).
Tiwari et al. teach that cyclodextrins including HP-b-CD/HP-bCD are well-known additives to peptide therapeutics to increase aqueous solubility, increase bioavailability, and increase stability (please refer to the entire reference particularly the abstract; “Advantages of Cyclodextrin Inclusion Complexation” section; “Peptide and protein delivery” subsection; “CD Applications in the Design of Some Novel Delivery Systems” section; “Cyclodextrin Effects on Important Drug Properties in Formulation” section).
Mehmood et al. teach lyophilized peptide formulations, methionine excipients, tartaric excipients, and cyclodextrin excipients (please refer to the entire reference particularly the abstract; sections 2, 4, and 5; Tables 3 and 7).
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." See 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.") and In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of th