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 .
Status of Claims
Claims 1-18 are pending and will be examined on the merits.
Claim Objections
Claim 13 is objected to because of the following informalities: Claim 13 recites an incorrect Markush group (see MPEP §2117). Examiner suggests amending claim 13 to read "wherein the antibiotic is selected from the group consisting of metronidazole, amoxycillin, tetracycline, erythromycin, clarithromycin, tinidazole, and combinations thereof" or "wherein the antibiotic is one or more of metronidazole, amoxycillin, tetracycline, erythromycin, clarithromycin, or tinidazole." Appropriate correction is required.
Claim 14 is objected to because of the following informalities: Claim 14 recites "wherein the isolated protein or the vector comprises a C. difficile Cwp2 protein or a fragment thereof." A vector cannot comprise a protein, it can encode a protein. Examiner suggests amending claim 14 to read "wherein the isolated protein comprises a C. difficile Cwp2 protein or a fragment thereof or the vector encodes a C. difficile Cwp2 protein or a fragment" or the like. Appropriate correction is required.
Claim 15 is objected to because of the following informalities: Claim 15 recites "wherein the adjuvant comprises alum, aluminum hydroxide or aluminum phosphate, wherein the . Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 10 and 12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10 recites "wherein the immunogenic composition elicits at least a B cell response, a CD4+ T cell response, including Th1, Th2, or Th17, or a CD8+ T cell response." It is unclear if the CD4+ T cell response is required to be one of the named responses, if it may be multiple of the named responses, or if those are simply possible options. Examiner suggests removing the phrase “including Th1, Th2, or Th17” to clarify the response options.
Claim 12 recites the limitation "at least one other pharmaceutical product" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 12 depends from claim 7, which recites an immunogenic composition comprising a C. difficile Cwp2 protein and a pharmaceutically acceptable carrier, adjuvant, or a combination thereof. Claim 7 does not recite a pharmaceutical product. It is unclear if claim 12 requires an additional pharmaceutical product to that recited in the claim or not. Examiner suggests removing the word “other” if there is no other pharmaceutical product required, or defining the first pharmaceutical product that is required. For purposes of examination, Examiner will interpret claim 12 as requiring one or more additional pharmaceutical products. It is additionally unclear if the “one other pharmaceutical product” is administered in combination with the instant invention or if it is formulated as part of the composition. Appropriate clarification is needed.
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.
Claims 1-7 and 9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (or naturally occurring product) without significantly more. The claim(s) recite(s) a naturally occurring protein. This judicial exception is not integrated into a practical application because the claims are drawn to a product, not a method. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not recite significant changes or additions to the naturally occurring state of the product. The following analysis is laid out in accordance with MPEP §2106:
Applicant’s claims recite an isolated protein comprising a surface component of C. difficile, wherein the component comprises surface proteins or colonization factors. Therefore, the claim is directed to a composition of matter, which is one of the statutory categories of invention (Step 1: yes).
The claims are then analyzed to determine whether it is directed to any judicial exception. In this case, the claim is directed to a naturally occurring protein, a surface protein or colonization factor produced by naturally occurring organism C. difficile. Claims 2-6 further limit the protein to, specifically, Cwp2, a cell wall protein. Claims 4-6 recite the sequence of the protein or the encoding nucleic acid, which are identical to the sequences found encoding the protein in the C. difficile genome (see Sequence Alignment 1 below). Therefore, the claims recite a naturally occurring product.
Next, the claims as a whole are analyzed to determine whether any element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception. Claims 1-6 do not recite any additional elements except the protein; therefore, claims 1-6 are only drawn to the judicial exception and are not eligible for patenting under 35 USC §101. Claim 7 recites an immunogenic composition comprising the same Cwp2 protein and a pharmaceutically acceptable carrier or an adjuvant. A pharmaceutically acceptable carrier reads on water, which is a naturally occurring substance, and simply adding a protein to water does not impart any special characteristics on said protein. Therefore, claim 7 does not amount to significantly more than the judicial exception, and is not patent eligible under 35 USC §101. Finally, claim 9 recites the immunogenic composition of claim 7, and recites the same SEQ ID NO for the Cwp2 protein as above. As demonstrated above, this sequence is identical to the naturally occurring protein. Thus, claim 9 does not add any distinguishing features that amount to significantly more than the judicial exception, and is not patent eligible under 35 USC §101.
Sequence Alignment 1 – SEQ ID NO: 18 and UniProt entry A0A9R0BMD3_CLODR
PNG
media_image1.png
783
600
media_image1.png
Greyscale
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-11, and 14-18 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by WO 2012/092469, Berry et al., published 07/05/2012, as evidenced by Tickler et al., Microorganisms 2025, 13, 2376.
The first set of instant claims recite an isolated protein comprising a surface component of C. difficile, wherein the component comprises surface proteins or colonization factors, wherein this protein is from a specific type of strain of C. difficile, wherein the protein is Cwp2, and has a sequence of SEQ ID NO:18 or a fragment thereof, is encoded by SEQ ID NO: 1, or comprises a specific fragment, Cwp2_A, represented by SEQ ID NO: 17. The second set of claims refer to an immunogenic composition comprising the same Cwp2 protein and a pharmaceutically acceptable carrier or an adjuvant, wherein the adjuvant is alum, aluminum hydroxide, or aluminum phosphate, the composition elicits a B cell or T cell response, the carrier comprises a nanoparticle or liposome, and the immunogenic composition further comprises an antibiotic such as metronidazole. The final set of instant claims refer to a method of treating or preventing C. difficile infection in a subject, comprising administering to the subject a vaccine comprising the same Cwp2 protein or a vector encoding such a protein, with a carrier or adjuvant, and wherein the vaccine is administered intravenously, intramuscularly, intradermally, or subcutaneously to the subject, or wherein the vector is a plasmid or an expression vector.
Berry et al. disclose compositions and methods for the treatment or prevention of C. difficile infection in a subject comprising a C. difficile spore polypeptide or fragment, and name the “SlpA paralogue”, represented by Berry SEQ ID NO: 5 and encoded by Berry SEQ ID NO: 20, as one of these proteins. This protein is the same as the instantly claimed Cwp2 protein, as evidenced by the sequence alignments below.
Sequence Alignment 2: SEQ ID NO: 1 and Berry et al. SEQ ID NO:20
Query Match 100.0%; Score 1872; Length 1872;
Best Local Similarity 100.0%;
Matches 1872; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGAATAAAAAAAATCTTTCTGTAATTATGGCTGCTGCAATGATAAGTACATCAGTAGCT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGAATAAAAAAAATCTTTCTGTAATTATGGCTGCTGCAATGATAAGTACATCAGTAGCT 60
Qy 61 CCAGTTTTTGCTGCAGAAACTACACAGGTAAAAAAAGAAACAATAACTAAGAAAGAAGCT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CCAGTTTTTGCTGCAGAAACTACACAGGTAAAAAAAGAAACAATAACTAAGAAAGAAGCT 120
Qy 121 ACAGAACTAGTTTCGAAAGTTAGAGATTTAATGTCTCAAAAGTATACTGGTGGTTCTCAA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ACAGAACTAGTTTCGAAAGTTAGAGATTTAATGTCTCAAAAGTATACTGGTGGTTCTCAA 180
Qy 181 GTTGGACAACCAATATATGAAATAAAAGTTGGCGAGACTTTATCAAAATTAAAAATAATA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GTTGGACAACCAATATATGAAATAAAAGTTGGCGAGACTTTATCAAAATTAAAAATAATA 240
Qy 241 ACTAATATAGATGAATTAGAGAAATTAGTAAATGCTTTGGGAGAAAATAAAGAACTTATT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 ACTAATATAGATGAATTAGAGAAATTAGTAAATGCTTTGGGAGAAAATAAAGAACTTATT 300
Qy 301 GTAACTATAACAGATAAAGGGCATATAACAAATAGTGCAAATGAAGTAGTTGCAGAAGCA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GTAACTATAACAGATAAAGGGCATATAACAAATAGTGCAAATGAAGTAGTTGCAGAAGCA 360
Qy 361 ACTGAAAAATATGAAAATTCAGCAGACCTTTCCGCTGAGGCTAATTCTATAACAGAAAAA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ACTGAAAAATATGAAAATTCAGCAGACCTTTCCGCTGAGGCTAATTCTATAACAGAAAAA 420
Qy 421 GCTAAAACTGAAACTAATGGAATTTATAAAGTTGCAGATGTAAAAGCTTCATATGATAGT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GCTAAAACTGAAACTAATGGAATTTATAAAGTTGCAGATGTAAAAGCTTCATATGATAGT 480
Qy 481 GCTAAAGATAAGTTAGTTATAACTTTAAGAGATAAAACAGACACAGTAACTTCTAAAACT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GCTAAAGATAAGTTAGTTATAACTTTAAGAGATAAAACAGACACAGTAACTTCTAAAACT 540
Qy 541 ATAGAGATAGGTATTGGTGATGAAAAAATTGATTTAACAGCAAATCCAGTTGATTCAACG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 ATAGAGATAGGTATTGGTGATGAAAAAATTGATTTAACAGCAAATCCAGTTGATTCAACG 600
Qy 601 GGAACAAACTTAGACCCTTCTACAGAAGGATTTAGAGTAAATAAAATCGTTAAACTAGGT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 GGAACAAACTTAGACCCTTCTACAGAAGGATTTAGAGTAAATAAAATCGTTAAACTAGGT 660
Qy 661 GTAGCAGGAGCTAAAAATATTGATGATGTCCAATTAGCTGAAATAACTATAAAAAATAGT 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 GTAGCAGGAGCTAAAAATATTGATGATGTCCAATTAGCTGAAATAACTATAAAAAATAGT 720
Qy 721 GACCTAAATACAGTTTCACCACAAGATTTATATGATGGATATAGATTAACTGTTAAAGGT 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GACCTAAATACAGTTTCACCACAAGATTTATATGATGGATATAGATTAACTGTTAAAGGT 780
Qy 781 AATATGGTAGCAAATGGAACATCAAAGTCAATTAGTGATATTTCATCAAAAGATTCAGAA 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 AATATGGTAGCAAATGGAACATCAAAGTCAATTAGTGATATTTCATCAAAAGATTCAGAA 840
Qy 841 ACAGGAAAGTATAAATTTACTATTAAGTATACTGATGCATCTGGAAAAGCAATAGAGCTT 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 ACAGGAAAGTATAAATTTACTATTAAGTATACTGATGCATCTGGAAAAGCAATAGAGCTT 900
Qy 901 ACTGTAGAAAGTACTAATGAAAAAGATTTAAAAGATGCCAAAGCTGCATTAGAAGGTAAT 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 ACTGTAGAAAGTACTAATGAAAAAGATTTAAAAGATGCCAAAGCTGCATTAGAAGGTAAT 960
Qy 961 TCAAAGGTTAAATTGATAGCTGGAGATGATAGATATGCAACTGCAGTGGCTATAGCAAAA 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 TCAAAGGTTAAATTGATAGCTGGAGATGATAGATATGCAACTGCAGTGGCTATAGCAAAA 1020
Qy 1021 CAAACAAAATATACTGACAATATAGTTATAGTTAATTCAAATAAACTAGTTGATGGATTA 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 CAAACAAAATATACTGACAATATAGTTATAGTTAATTCAAATAAACTAGTTGATGGATTA 1080
Qy 1081 GCAGCTACACCACTTGCTCAATCTAAAAAAGCACCTATATTATTAGCATCCGATAATGAA 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 GCAGCTACACCACTTGCTCAATCTAAAAAAGCACCTATATTATTAGCATCCGATAATGAA 1140
Qy 1141 ATACCAAAAGTAACTTTAGATTATATAAAAGATATAATTAAGAAAAGCCCATCAGCTAAA 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 ATACCAAAAGTAACTTTAGATTATATAAAAGATATAATTAAGAAAAGCCCATCAGCTAAA 1200
Qy 1201 ATATATATAGTAGGTGGAGAATCAGCAGTATCAAATACAGCTAAAAAGCAATTAGAATCA 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 ATATATATAGTAGGTGGAGAATCAGCAGTATCAAATACAGCTAAAAAGCAATTAGAATCA 1260
Qy 1261 GTAACTAAGAATGTTGAAAGACTAGCTGGAGATGATAGACATATGACTTCTGTAGCAGTA 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1261 GTAACTAAGAATGTTGAAAGACTAGCTGGAGATGATAGACATATGACTTCTGTAGCAGTA 1320
Qy 1321 GCAAAAGCTATGGGGTCTTTTAAAGATGCATTTGTAGTAGGTGCGAAAGGGGAGGCTGAT 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1321 GCAAAAGCTATGGGGTCTTTTAAAGATGCATTTGTAGTAGGTGCGAAAGGGGAGGCTGAT 1380
Qy 1381 GCTATGAGTATAGCTGCCAAAGCTGCTGAACTTAAGGCTCCTATAATAGTAAATGGCTGG 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1381 GCTATGAGTATAGCTGCCAAAGCTGCTGAACTTAAGGCTCCTATAATAGTAAATGGCTGG 1440
Qy 1441 AATGATCTTTCAGCAGACGCTATCAAATTGATGGATGGAAAAGAGATTGGTATAGTTGGT 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1441 AATGATCTTTCAGCAGACGCTATCAAATTGATGGATGGAAAAGAGATTGGTATAGTTGGT 1500
Qy 1501 GGTTCTAACAATGTATCTAGTCAAATTGAAAATCAACTTGCTGATGTTGATAAAGATAGA 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1501 GGTTCTAACAATGTATCTAGTCAAATTGAAAATCAACTTGCTGATGTTGATAAAGATAGA 1560
Qy 1561 AAAGTTCAAAGAGTTGAAGGAGAAACAAGACACGATACTAATGCTAAGGTTATAGAAACA 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1561 AAAGTTCAAAGAGTTGAAGGAGAAACAAGACACGATACTAATGCTAAGGTTATAGAAACA 1620
Qy 1621 TATTATGGAAAATTAGATAAACTATATATAGCAAAAGATGGATATGGAAATAATGGTATG 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1621 TATTATGGAAAATTAGATAAACTATATATAGCAAAAGATGGATATGGAAATAATGGTATG 1680
Qy 1681 CTAGTAGATGCATTGGCAGCAGGACCTCTAGCAGCAGGTAAAGGTCCAATACTTCTAGCT 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1681 CTAGTAGATGCATTGGCAGCAGGACCTCTAGCAGCAGGTAAAGGTCCAATACTTCTAGCT 1740
Qy 1741 AAAGCTGATATAACAGACTCACAAAGGAATGCACTTAGTAAAAAATTAAATCTTGGTGCA 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1741 AAAGCTGATATAACAGACTCACAAAGGAATGCACTTAGTAAAAAATTAAATCTTGGTGCA 1800
Qy 1801 GAAGTAACTCAAATAGGTAATGGAGTTGAATTGACAGTAATACAAAAGATAGCTAAAATA 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1801 GAAGTAACTCAAATAGGTAATGGAGTTGAATTGACAGTAATACAAAAGATAGCTAAAATA 1860
Qy 1861 CTAGGTTGGTAA 1872
||||||||||||
Db 1861 CTAGGTTGGTAA 1872
Sequence Alignment 3: SEQ ID NO: 18 and Berry et al. SEQ ID NO: 20 (attached)
Sequence Alignment 4: SEQ ID NO: 18 and Berry et al. SEQ ID NO: 5
Query Match 96.8%; Score 2967; Length 620;
Best Local Similarity 98.7%;
Matches 604; Conservative 2; Mismatches 6; Indels 0; Gaps 0;
Qy 12 AAMISTSVAPVFAAETTQVKKETITKKEATELVSKVRDLMSQKYTGGSQVGQPIYEIKVG 71
| :||| : ||||||||||||||||||||||||||||||||||||||||||||||||
Db 9 ALVISTCLEFSMAAETTQVKKETITKKEATELVSKVRDLMSQKYTGGSQVGQPIYEIKVG 68
Qy 72 ETLSKLKIITNIDELEKLVNALGENKELIVTITDKGHITNSANEVVAEATEKYENSADLS 131
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 69 ETLSKLKIITNIDELEKLVNALGENKELIVTITDKGHITNSANEVVAEATEKYENSADLS 128
Qy 132 AEANSITEKAKTETNGIYKVADVKASYDSAKDKLVITLRDKTDTVTSKTIEIGIGDEKID 191
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 129 AEANSITEKAKTETNGIYKVADVKASYDSAKDKLVITLRDKTDTVTSKTIEIGIGDEKID 188
Qy 192 LTANPVDSTGTNLDPSTEGFRVNKIVKLGVAGAKNIDDVQLAEITIKNSDLNTVSPQDLY 251
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 189 LTANPVDSTGTNLDPSTEGFRVNKIVKLGVAGAKNIDDVQLAEITIKNSDLNTVSPQDLY 248
Qy 252 DGYRLTVKGNMVANGTSKSISDISSKDSETGKYKFTIKYTDASGKAIELTVESTNEKDLK 311
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 249 DGYRLTVKGNMVANGTSKSISDISSKDSETGKYKFTIKYTDASGKAIELTVESTNEKDLK 308
Qy 312 DAKAALEGNSKVKLIAGDDRYATAVAIA KQTKYTDNIVIVNSNKLVDGLAATPLAQSKKA 371
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 309 DAKAALEGNSKVKLIAGDDRYATAVAIA KQTKYTDNIVIVNSNKLVDGLAATPLAQSKKA 368
Qy 372 PILLASDNEIPKVTLDYIKDIIKKSPSAKIYIVGGESAVSNTAKKQLESVTKNVERLAGD 431
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 369 PILLASDNEIPKVTLDYIKDIIKKSPSAKIYIVGGESAVSNTAKKQLESVTKNVERLAGD 428
Qy 432 DRHMTSVAVAKAMGSFKDAFVVGAKGEADAMSIAAKAAELKAPIIVNGWNDLSADAIKLM 491
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 429 DRHMTSVAVAKAMGSFKDAFVVGAKGEADAMSIAAKAAELKAPIIVNGWNDLSADAIKLM 488
Qy 492 DGKEIGIVGGSNNVSSQIENQLADVDKDRKVQRVEGETRHDTNAKVIETYYGKLDKLYIA 551
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 489 DGKEIGIVGGSNNVSSQIENQLADVDKDRKVQRVEGETRHDTNAKVIETYYGKLDKLYIA 548
Qy 552 KDGYGNNGMLVDALAAGPLAAGKGPILLAKADITDSQRNALSKKLNLGAEVTQIGNGVEL 611
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 549 KDGYGNNGMLVDALAAGPLAAGKGPILLAKADITDSQRNALSKKLNLGAEVTQIGNGVEL 608
Qy 612 TVIQKIAKILGW 623
||||||||||||
Db 609 TVIQKIAKILGW 620
Sequence Alignment 5: SEQ ID NO: 17 and Berry et al. SEQ ID NO: 5
Qy 1 QVKKETITKKEATELVSKVRDLMSQKYTGGSQVGQPIYEIKVGETLSKLKIITNIDELEK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 26 QVKKETITKKEATELVSKVRDLMSQKYTGGSQVGQPIYEIKVGETLSKLKIITNIDELEK 85
Qy 61 LVNALGENKELIVTITDKGHITNSANEVVAEATEKYENSADLSAEANSITEKAKTETNGI 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 86 LVNALGENKELIVTITDKGHITNSANEVVAEATEKYENSADLSAEANSITEKAKTETNGI 145
Qy 121 YKVADVKASYDSAKDKLVITLRDKTDTVTSKTIEIGIGDEKIDLTANPVDSTGTNLDPST 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 146 YKVADVKASYDSAKDKLVITLRDKTDTVTSKTIEIGIGDEKIDLTANPVDSTGTNLDPST 205
Qy 181 EGFRVNKIVKLGVAGAKNIDDVQLAEITIKNSDLNTVSPQDLYDGYRLTVKGNMVANGTS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 206 EGFRVNKIVKLGVAGAKNIDDVQLAEITIKNSDLNTVSPQDLYDGYRLTVKGNMVANGTS 265
Qy 241 KSISDISSKDSETGKYKFTIKYTDASGKAIELTVESTNEKDLKDAKAALE 290
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 266 KSISDISSKDSETGKYKFTIKYTDASGKAIELTVESTNEKDLKDAKAALE 315
As shown by these sequence alignments, Berry et al. disclose an isolated protein comprising a surface component of C. difficile, which comprises a Cwp2 protein that comprises SEQ ID NO:17, SEQ ID NO:18, and is encoded by SEQ ID NO: 1, therefore anticipating claims 1 and 3-6. Additionally, Berry et al. disclose, in Example 3 on page 63 and in paragraph [00192] that the sequence for the protein is from strain R20291. Tickler et al., 2025, discloses that strain R20291 is a RT027 strain (see Figure 2 caption), and so Berry et al. also teach the limitations of instant claim 2.
Berry et al. disclose a composition comprising this protein and a pharmaceutically acceptable carrier in Berry claim 39, thereby teaching claim 7. Berry et al. also disclose addition of an adjuvant in paragraph [00141], including alum, aluminum hydroxide, and aluminum phosphate, anticipating claim 8. Paragraph [00149] of Berry et al. disclose that the carrier may be a nanoparticle or a liposome, anticipating claim 11. Examples 6, 7, and 10 of Berry et al. demonstrates robust production of antibodies upon immunization with the Cwp2 protein. As antibody production is a hallmark of B cell response, it is clear this immunogenic composition can elicit a B cell response, teaching claim 10.
Claim 30 of Berry et al. disclose a method of reducing or preventing C. difficile infection in a subject in need thereof comprising administering the Cwp2 protein and an adjuvant in an effective amount, anticipating claim 14. As discussed above, this adjuvant may be alum, aluminum hydroxide or aluminum phosphate, anticipating instant claim 15. Claim 32 of Berry et al. disclose oral, intranasal, intravenous, or intramuscular administration of the composition, anticipating instant claim 16. Berry et al. teach, in claim 49 and 50, a method of reducing or preventing C. difficile infection by administering a nucleic acid encoding the Cwp2 protein and an adjuvant to a subject. Berry et al. also teach, in claim 63, an expression vector encoding Cwp2. Additionally, Example 3 of Berry et al. teaches the creation of plasmid encoding the Cwp2 protein and example 8 of Berry et al. teaches immunizing hamsters with these plasmids, thereby teaching instant claim 17. Finally, as seen in the sequence alignments above and attached, the protein of Berry et al. comprises a sequence of SEQ ID NO: 18 and SEQ ID NO: 1, therefore anticipating instant claim 18.
Therefore, Berry et al. anticipates instant claims 1-11 and 14-18.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Berry et al., as evidenced by Tickler et al.
The first set of instant claims recite an isolated protein comprising a surface component of C. difficile, wherein the component comprises surface proteins or colonization factors, wherein this protein is from a specific type of strain of C. difficile, wherein the protein is Cwp2, and has a sequence of SEQ ID NO:18 or a fragment thereof, is encoded by SEQ ID NO: 1, or comprises a specific fragment, Cwp2_A, represented by SEQ ID NO: 17. The second set of claims refer to an immunogenic composition comprising the same Cwp2 protein and a pharmaceutically acceptable carrier or an adjuvant, wherein the adjuvant is alum, aluminum hydroxide, or aluminum phosphate, the composition elicits a B cell or T cell response, the carrier comprises a nanoparticle or liposome, and the immunogenic composition further comprises an antibiotic such as metronidazole. The final set of instant claims refer to a method of treating or preventing C. difficile infection in a subject, comprising administering to the subject a vaccine comprising the same Cwp2 protein or a vector encoding such a protein, with a carrier or adjuvant, and wherein the vaccine is administered intravenously, intramuscularly, intradermally, or subcutaneously to the subject, or wherein the vector is a plasmid or an expression vector.
Berry et al. disclose compositions and methods for the treatment or prevention of C. difficile infection in a subject comprising a C. difficile spore polypeptide or fragment, and name the “SlpA paralogue”, represented by Berry SEQ ID NO: 5 and encoded by Berry SEQ ID NO: 20, as one of these proteins. This protein is the same as the instantly claimed Cwp2 protein, as evidenced by the sequence alignments above.
As shown by these sequence alignments, Berry et al. disclose an isolated protein comprising a surface component of C. difficile, which comprises a Cwp2 protein that comprises SEQ ID NO:17, SEQ ID NO:18, and is encoded by SEQ ID NO: 1, therefore teaching claims 1 and 3-6. Additionally, Berry et al. disclose, in Example 3 on page 63 and in paragraph [00192] that the sequence for the protein is from strain R20291. Tickler et al., 2025, discloses that strain R20291 is a RT027 strain (see figure 2 caption), and so Berry et al. also teach the limitations of instant claim 2.
Berry et al. disclose a composition comprising this protein and a pharmaceutically acceptable carrier in Berry claim 39, thereby teaching claim 7. Berry et al. also disclose addition of an adjuvant in paragraph [00141], including alum, aluminum hydroxide, and aluminum phosphate, teaching claim 8. Paragraph [00149] of Berry et al. disclose that the carrier may be a nanoparticle or a liposome, teaching claim 11. Examples 6, 7, and 10 of Berry et al. demonstrates robust production of antibodies upon immunization with the Cwp2 protein. As antibody production is a hallmark of B cell response, it is clear this immunogenic composition can elicit a B cell response, teaching claim 10.
Claim 30 of Berry et al. disclose a method of reducing or preventing C. difficile infection in a subject in need thereof comprising administering the Cwp2 protein and an adjuvant in an effective amount, teaching claim 14. As discussed above, this adjuvant may be alum, aluminum hydroxide or aluminum phosphate, teaching instant claim 15. Claim 32 of Berry et al. disclose oral, intranasal, intravenous, or intramuscular administration of the composition, teaching instant claim 16. Berry et al. teach, in claim 49 and 50, a method of reducing or preventing C. difficile infection by administering a nucleic acid encoding the Cwp2 protein and an adjuvant to a subject. Berry et al. also teach, in claim 63, an expression vector encoding Cwp2. Additionally, Example 3 of Berry et al. teaches the creation of plasmid encoding the Cwp2 protein and example 8 of Berry et al. teaches immunizing hamsters with these plasmids, thereby teaching instant claim 17. Finally, as seen in the sequence alignments above, the protein of Berry et al. comprises a sequence of SEQ ID NO: 18 and SEQ ID NO: 1, therefore teaching instant claim 18.
Berry et al. do not explicitly teach addition of an antibiotic to the immunogenic composition, and also do not explicitly teach administering a vector encoding the Cwp2 protein or a fragment.
However, Berry et al. do teach administering antibodies to the Cwp2 protein, among other C. difficile antigens, and recite in paragraph [0017] and claims 14-15, that the antibody composition may further contain an antibiotic, and that antibiotic may be metronidazole, such as in instant claims 12 and 13. Berry et al. also teach using this composition in a method of treating C. difficile infection, in paragraph [00209] of example 9. Specifically, example 9B discloses that antibiotics combined with antibodies to spore antigens prevents relapse and lessen bacterial shedding. Example 8 of Berry et al., which disclose immunizing hamsters with the antigen (in both nucleic acid and protein form) is predicted to reduce the shedding of spores and result in improved survival upon challenge with C. difficile. Taken together, as the two compositions of Berry et al. (the vaccine in claim 8 and the antibodies and antibiotics of claim 9) have different advantages, (preventing infection, treating infection, and preventing relapse), it would be obvious to one of ordinary skill in the art to administer both compounds. One would be motivated to do so because the vaccine provides the advantage of improved survival upon exposure to C. difficile, and the antibodies and antibiotics have the advantage of preventing relapse, while both of the advantage of lessening bacterial and spore shedding. One would have a reasonable expectation of success as the compositions are both shown to work in the examples of Berry et al.
As discussed under paragraph 9 of this office action, the use of the phrase “comprises at least one other pharmaceutical product” indicates that more than one additional pharmaceutical product can be administered with the immunogenic composition of instant claim 7, and the term “product” indicates these can be administered in combination with the instant invention or formulated as part of the composition. Therefore, administration of both the vaccine and the antibody and antibiotic compositions of Berry et al. teaches instant claims 12 and 13.
Taken together, claims 1-18 are obvious in view of Berry et al.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amelia Stephens whose telephone number is (571)272-1006. The examiner can normally be reached M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AMELIA STEPHENS/
Examiner, Art Unit 1645
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
Prosecution Insights