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 .
Response to Amendment
The amendment filed 2/9/2026 has been entered.
Claims 1, 9, 33, 39, 49, 53 and 68 have been amended. Claims 1-3, 9-10, 14-15, 19-20, 24-25, 27, 30-33, 35, 39-40, 45, 49-50, 53, 57, 60-66, 68-69, 75-78, 80, 83 and 85-87 are pending.
Claims 1-3, 9-10, 14-15, 19-20, 24-25, 27, 33,35, 39-40, 45, 49-50, 53, 57, 64-66, 68-69, 77-78 and 80 are under examination
Claims 30-32, 60-63, 75-76 and 85-87 are withdrawn.
Claim Rejections Withdrawn
The rejection of claims 1, 14, 27, 34, 39, 49, 64, and 80 under 35 U.S.C. 101 is withdrawn in view of the amendment to the claims.
The rejection of claims 1, 14, 27, 34, 39, 49, 64 and 80 under 35 U.S.C. 102(a)(1) as being anticipated by Morinaga et al. Microbiol Immunol 47:81-90 (2003) is withdrawn in view of the amendment to the claims.
The rejection of claims 8, 34, 44 and 52 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10, 12-16, 19-27, 29-30, 33-38, 40, 42, 45, 46, 48 and 49-53 of copending Application No. 18/551,830 (‘830) is withdrawn in view of the cancellation of the claims.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
The rejection of claims 33, 35, 57, 65 and 77 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more is maintained.
The claim(s) recite(s):
Claim 33 is drawn to a variant Staphylococcus aureus Leukocidin B (LukB) protein or polypeptide of SEQ ID NO: 39, said LukB variant polypeptide comprising: an amino acid substitution at the amino acid residue corresponding to amino acid residue Val53 of SEQ ID NO: 39, wherein the amino acid substitution at the amino acid residue Val53 comprises a valine to leucine (Val53Leu) substitution.
Claim 65 recites the vaccine composition of claim 64, wherein the lukA variant polypeptide is a variant of SEQ ID NO: 1.
The claims are drawn to a composition of matter. This is because the LukA and LukB variant encompasses natural variants that comprises one or more of the stated amino acid substitutions.
Claim 65 recites wherein the lukA variant polypeptide is a variant of SEQ ID NO: 1. This is broadly recited and reads on a variant of SEQ ID NO: 1. The variant of LukA is a S. aureus LukEv protein is set forth in Appendix A sequence alignment with SEQ ID NO: 1.
In claim 33, drawn to the LukB variant, the LukB variant is a S. aureus LukDv protein which comprise one or more of the corresponding amino acid substitutions (see Appendix B sequence alignment with SEQ ID NO: 16, cited previously).
STEP 2A PRONG ONE – THE CLAIM RECITES A JUDICIAL EXCEPTION -SEE MPEP 2106.4
LukDv and LukEv are S. aureus proteins and are thus judicial exceptions. A composition comprising both LukDv and LukEv encompasses the S. aureus bacteria. Morinaga et al (cited in PTO-892) discloses that S. aureus expresses both protein. Thus the composition comprising both LukDv and LukEv is a S. aureus bacteria which is a product of nature and thus is a judicial exception. Morinaga et al and the sequence annotation for both proteins disclose that each protein naturally comprises a signal sequence.
The claims do not recite additional elements that integrate the judicial exception(s) into a practical application such a particular treatment or prophylaxis for a disease or medical condition i.e. affirmatively reciting an action that effects a particular treatment or prophylaxis for a disease or medical condition. An example of said action is a step of administering the bacterium or the composition comprising the bacterium to a subject and not merely an intended use of the bacteria. See MPEP 2106.04(d)(2).
Next, the claims a whole is analyzed to determine whether any additional element, or combinations of elements, is sufficient to ensure that the claim amounts to significantly more than the exceptions. Integration requires an additional element in the claim to apply, rely on, or use the judicial exception in a manner than imposes a meaningful limit on the judicial exception. The claims do not recite any meaningful additional limitations, modification(s) or transformation(s) that sufficiently ensures that the claim amounts to significantly more than the exceptions.
Thus, the claims as a whole does not amount to significantly more than the “product of nature” by itself. Thus, the claims does not qualify as eligible subject matter under 35 USC 101.
Response to Arguments
Applicant’s argument that the valine to a leucine substitution at the amino acid residue corresponding to Val53 in the consensus sequence SEQ ID NO: 39 is not found is not persuasive. Applicants state that as shown in figure 2 that 14 different S. aureus lukB sequences have a Val at position corresponding to Val53 of the consensus sequence SEQ ID NO: 39. This argument is also not found persuasive because it is referring to sequences in the specification and not to the limitations of how claim 33 is written.
Claim 33 is drawn to a “variant S. aureus LukB protein or polypeptide of SEQ ID NO: 39”.
The protein set forth in the sequence alignment Appendix B is a variant S. aureus LukB protein or polypeptide of SEQ ID NO: 39 which comprises an amino acid substitution at the amino acid residue corresponding to amino acid Val 53 of SEQ ID NO: 39, wherein the substitution is Val53Leu.
SEQ ID NO: 39 is a consensus sequence and thus Appendix B is a sequence alignment with SEQ ID NO: 16 which is a LukB sequence which is part of the 14 S. aureus LukB sequences used to generate the consensus sequence SEQ ID NO: 39.
As seen in the Appendix B, there is the Val53Leu substitution a position 53.
Claim 65 recites wherein the lukA variant polypeptide is a variant of SEQ ID NO: 1. This is broadly recited and reads on a variant of SEQ ID NO: 1. The variant is S. aureus LukEv protein which is set forth in Appendix A sequence alignment with SEQ ID NO: 1.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The rejection of claim(s) 33, 35, 57, 65 and 77 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Morinaga et al. Microbiol Immunol 47:81-90 (2003).
Claim 33 and 35: Morinaga et al disclose a variant S. aureus Leukocidin B (LukB) polypeptide of SEQ ID NO: 39, said LukB variant polypeptide comprising an amino acid substitution at the amino acid residue corresponding to amino acid residues Val(V)53 of SEQ ID NO: 39, wherein the substitutions is V53L (Leu) of the LukB variant of Morinaga et al (LukDv). See appendix B alignment of SEQ ID NO: 16 which is a species of the genus of claim 39 with the amino acid sequence of LukDv of Morinaga et al.
Claim 57: Morinaga et al disclose the LukB variant (LukDv) further comprises an amino terminal signal sequence or amino acid purification tag at the N-terminus.
See sequence alignment annotation and Morinaga et al disclosing LukDv without signal peptide. See p. 82 under “cloning of LukEv and LukDv” and “Recombinant LukEv and LukDv proteins”. Morinaga et al also disclose the LukB variant comprises 6 histidines at the N-terminal by virtue of cloning into the pet14b expression vector which expresses proteins with the his-tag at the N-terminal of the expressed protein.
Claim 77: Morinaga et al disclose a Staphylococcus aureus vaccine composition comprising the LukB variant. See p. 82 under “recombinant LukEv and LukDv proteins”.
Claim 65: Morinaga et al disclose a variant S. aureus Leukocidin A (LukA) polypeptide of SEQ ID NO: 25, said LukA variant polypeptide comprising an amino acid substitution at one or more amino acid residues corresponding to amino acid residues Lys83, Ser141, Val113, wherein the substitutions are L80M, V110I and S138Q of the LukA variant of Morinaga et al. See Appendix A for the sequence alignment of SEQ ID NO: 1 which is a species of the genus of claim 1 with the LukEv amino acid sequence of Morinaga et al. The LukA variant polypeptide is a variant of SEQ ID NO: 1.
See sequence alignment with SEQ ID NO: 1 in Appendix A.
Response to Arguments
Applicant’s argument that the valine to a leucine substitution at the amino acid residue corresponding to Val53 in the consensus sequence SEQ ID NO: 39 is not present is not found persuasive. Applicants argument that Moringa provides no teaching regarding LukB polypeptides per se and certainly no teaching of point mutations introduced at specific locations in the LukB amino acid sequence has been carefully considered but is not found persuasive. This argument is not found persuasive because it is referring to making point mutations in a LukB polypeptide and not to the limitations of how claim 33 is written.
Claim 33 is drawn to a “variant S. aureus LukB protein or polypeptide of SEQ ID NO: 39”.
The protein set forth in the sequence alignment Appendix B is a variant S. aureus LukB protein or polypeptide of SEQ ID NO: 39 which comprises an amino acid substitution at the amino acid residue corresponding to amino acid Val 53 of SEQ ID NO: 39, wherein the substitution is Val53Leu.
SEQ ID NO: 39 is a consensus sequence and thus Appendix B is a sequence alignment with SEQ ID NO: 16 which is a LukB sequence which is part of the 14 S. aureus LukB sequences used to generate the consensus sequence SEQ ID NO: 39.
As seen in the Appendix B, there is the Val53Leu substitution a position 53.
Claim 65 recites wherein the lukA variant polypeptide is a variant of SEQ ID NO: 1. This is broadly recited and reads on a variant of SEQ ID NO: 1. The variant is S. aureus LukEv protein which is set forth in Appendix A sequence alignment with SEQ ID NO: 1.
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 1-3, 9-10, 14-15, 19-20, 24-25, 33, 35, 39-40, 45, 49-50, 53, 64-66, 68-69, 77-78 and 80 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-8, 10, 12-16, 19-27, 29-30, 33-38, 40, 42, 45, 46, 48 and 49-53 of copending Application No. 18/551,830 (‘830). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘830 claims disclose:
Claim 1: The ‘830 claims disclose a variant Staphylococcus aureus Leukocidin A (LukA) polypeptide of SEQ ID NO:25, said LukA variant polypeptide comprising:
an amino acid substitution at one or more amino acid residues corresponding to amino acid residues Lys83, Ser141, Val113, and Vall193 of SEQ ID NO: 25.
Claim 2: The ‘830 claims disclose the LukA variant polypeptide further comprises: an amino acid substitution at the amino acid residue corresponding to Glu323 of SEQ ID NO: 25.
Claim 23: the ‘830 claims disclose that in the LukA variant polypeptide of claim 2, wherein the amino acid substitutions correspond to Glu323A, L83M, S141A, V113I and V193I of SEQ.
Claim 8-9. The ‘830 claims disclose that in the LukA variant polypeptide of claim 2, comprises all the amino acid substitutions corresponding to Glu323A, L83M, S141A, V113I and V193I of SEQ No 25.
Claim 10. The ‘830 claims disclose the LukA variant polypeptide is a CC8 LukA comprising the amino acid sequence of SEQ ID NO: 3.
Claims 14-15: The ‘830 claims disclose the LukA variant polypeptide of claim 1, further comprises: an amino acid substitution at one or more amino acid residues corresponding to amino acid residues Tyr74, Asp140, Gly149, and Gly156 of SEQ ID NO: 25 wherein the substitutions are Tyr74Cys, Asp140Cys, Gly149Cys, and Gly156Cys.
Claim 19. The ‘830 claims the LukA variant polypeptide of claim 14, wherein said LukA variant polypeptide comprises amino acid substitutions at each amino acid residue corresponding to amino acid residues Tyr74, Asp140, Gly149, and Gly156 of SEQ ID NO: 25.
Claim 20. The ‘830 claims disclose the LukA variant polypeptide of claim 14, wherein said variant is a CC8 LukA variant polypeptide comprising the amino acid sequence of SEQ ID NO: 5.
Claim 24. The ‘830 claims disclose the LukA variant polypeptide of claims 1, wherein said LukA variant polypeptide further comprises an amino acid substitution at the amino acid residue corresponding to amino acid residue Thr249 of SEQ ID NO: 25.
Claim 25. The ‘830 claims disclose the LukA variant polypeptide of claim 24, wherein the amino acid substitution at the amino acid residue corresponding to Thr249 comprises a threonine to valine (Thr249Val) substitution, or wherein said variant LukA protein comprises the amino acid sequence of SEQ ID NO: 7 or SEQ ID NO: 8.
Claim 33-35. The ‘830 claims disclose a variant Staphylococcus aureus Leukocidin B (LukB) protein or polypeptide of SEQ ID NO: 39, said LukB variant polypeptide comprises an amino acid substitution at the amino acid residue corresponding to amino acid residue Val53 of SEQ ID NO: 39, wherein the amino acid substitution Val53Leu substitution and wherein variant is a CC45 LukB variant of SEQ ID NO: 16 comprising the amino acid substitution corresponding to Val53Leu of SEQ ID NO: 16, or wherein said LukB variant polypeptide comprises the amino acid sequence of SEQ ID NO: 18.
Claims 39-40, 44-45, 49-50, 52, 53. The ‘830 claims disclose the LukB variant polypeptide of claim 33 wherein said variant further comprises an amino acid substitution at one or more amino acid residues corresponding to amino acid residues Glu45, Glu109, Thr121, and Arg154 of SEQ ID NO: 39; wherein the substitutions correspond to Glu45Cys, Glu109Cys, Thr121Cys, and Arg154Cys of SEQ ID NO: 39, wherein said LukB variant polypeptide comprises amino acid substitutions at each amino acid residue corresponding to amino acid residues Glu45, Glu109, Thr121, and Arg154 of SEQ ID NO: 39, wherein said variant is a CC45 LukB variant of SEQ ID NO: 16 comprising the amino acid substitutions corresponding to Val53Leu, Glu45Cys, Glul10Cys, Thr123Cys, and Arg155Cys of SEQ ID NO: 16, or wherein said LukB variant polypeptide comprises the amino acid sequence of SEQ ID NO: 20 or 22.
Claim 64,65. The ‘830 claims disclose a Staphylococcus aureus vaccine composition comprising: one or more variant LukA proteins or polypeptides of claim 1.
wherein the LukA variant polypeptide is a variant of SEQ ID NO: 1, wherein the variant comprises SEQ ID NO: 3.
Claim 66. The ‘830 claims disclose the vaccine composition of claim 64 further comprising: a leukocidin B (LukB) protein or polypeptide, said LukB protein or polypeptide having at least 85% sequence similarity to the amino acid sequence of SEQ ID NO: 16.
Claim 68-69. The ‘830 claims disclose the vaccine composition of claim 66 wherein the LukA variant polypeptide comprises an amino acid substitution at one or more amino acid residues corresponding to amino acid residues Lys80Met, Ser138Ala, Val110Ile, Val190Ile, Lys80, Serl38, Vall10, Val190, and Glu320Ala of SEQ ID NO: 1, wherein the variant comprises SEQ ID NO: 3 and the LukB polypeptide comprises the amino acid sequence of SEQ ID NO:18.
Claim 77. The ‘830 claims disclose a Staphylococcus aureus vaccine composition comprising: one or more variant LukB proteins or polypeptides of claim 33.
Claim 78. The ‘830 claims disclose the vaccine composition of claim 77 further comprising: a leukocidin A (LukA) protein or polypeptide, said LukA protein or polypeptide having at least 85% sequence similarity to the amino acid sequence of SEQ ID NO: 1 (CC8), wherein the LukA variant comprises SEQ ID NO: 3.
Claim 80. The ‘830 claims disclose a staphylococcus aureus vaccine composition comprising:
The LukA variant polypeptide of claim 1, and
The LukB variant polypeptide of SEQ ID NO: 39, said LukB variant polypeptide comprising:
(i) an amino acid substitution at the amino acid residue corresponding to
amino acid residue Val53 of SEQ ID NO: 39; or
(ii) an amino acid substitution at one or more amino acid residues
corresponding to amino acid residues Glu45, Glul09, Thr121, and Arg154 of SEQ ID NO: 39.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s Argument
Applicants argue that because the claims have an earlier patent term filing date and the provisional obviousness type rejection are the only remaining rejections, this rejection should be withdrawn. This has been considered but is not found persuasive because the provisional double patenting rejection is not the only remaining rejection.
The rejection of claims 27 and 57 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-8, 10, 12-16, 19-27, 29-30, 33-38, 40, 42, 45, 46, 48 and 49-53 of copending Application No. 18/551,830 (‘830) in view of Dobeli et al. US 5,310,663 5.10.94 is maintained.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘830 claims is set forth above but does not disclose the LukA and LukB variant comprises an amino terminus purification sequence.
Dobeli et al disclose affinity tags for the purification of a desired protein by linking the coding gene sequence of a desired protein to the coding gene sequence of the affinity tag and using recombinant technology to express the protein and recover the protein from host cells using chelate affinity chromatography. See whole document especially columns 1 and 2. Dobeli et al disclose the affinity tags are placed at the N-terminus of the protein of interest. See column 4 under fig. 21 and fig. 24.
It would have been prima facie obvious to one of ordinary skill in the art as of the effective filing date to have attached an affinity tag to the N-terminus of LukA and LukB variant amino acid sequences of the ‘830 claims by linking the coding gene sequence of a desired protein to the coding gene sequence of the affinity tag and using recombinant technology to express the protein and recover the protein from host cells using chelate affinity chromatography.
The motivation to do so is that Dobeli et al disclose that affinity tags can be used in the purification of recombinantly expressed proteins.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s Argument
Applicants argue that because the claims have an earlier patent term filing date and the provisional obviousness type rejection are the only remaining rejections, this rejection should be withdrawn. This has been considered but is not found persuasive because the provisional double patenting rejection is not the only remaining rejection.
Status of Claims
Claims 1-3, 9-10, 14-15, 19-20, 24-25, 27, 33, 35, 39-40, 45, 49-50, 53, 57, 64-66, 68-69, 77-78 and 80 are rejected. Claims 30-32, 60-63, 75-76, 83 and 85-87 are withdrawn.
Claims 1-3, 9-10, 14-15, 19-20, 24-25, 27, 33,35, 39-40, 45, 49-50, 53, 57, 64-66, 68-69, 77-78 and 80 are under examination
Claims 30-32, 60-63, 75-76, 83 and 85-87 are withdrawn.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/OLUWATOSIN A OGUNBIYI/Primary Examiner, Art Unit 1645