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 .
Claims 1-20 are pending and currently under consideration.
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 1-20 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.
Claims 1-20 are rejected because it is unclear how, or if, the term “high-affinity” in parenthesis, the term “low-affinity” in parenthesis, and the recited SEQ ID NOs in parenthesis limit the claims.
Claims 6-8, and 19 are rejected because claim 6 recites “…wherein the substitution comprises…substituted for a leucine, tyrosine, phenylalanine, and/or a valine”, claim 7 recites “…and the substitution is at L34, V35, and/or Y64…”, claim 8 recites “…and the substation is at L32, V33, and/or F63…”, and claim 19 recites “…and the substation comprises L32, V33, and F63….” Claim 6-8, and 19 each depend on independent claims that describe a single substation (“the substation”) as a substitution of a single amino acid for another single amino acid (see independent claims 1 and 12). Therefore, it is unclear what is meant by a substation of a single amino acid of the independent claims comprising a substation of multiple amino acids in the dependent claims.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 8 and 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. In the instant case, the claims are inclusive of (i) a genus E. coli FmIH proteins comprising an L32, V33, and/or F63 substitution that are in an active conformation and (b) a genus E. coli FmIH proteins comprising an L32, V33, and/or F63 substitution that are in an inactive conformation. However, the written description in this case only sets forth V33E FmIH and F63E FmIH as E. coli FmIH proteins comprising an L32, V33, and/or F63 substitution that are in an active conformation and (b) L32E FmIH as an E. coli FmIH protein comprising an L32, V33, and/or F63 substitution that is in an inactive conformation (see paragraph spanning pages 39-40, in particular). The specification does not disclose, and the art does not teach, the genera as broadly encompassed in the claims.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common to that genus that “constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997): “A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNA, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus.”
The inventions at issue in Lilly were DNA constructs per se, the holdings of that case is also applicable to claims such as those at issue here. Further, disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product. See Ariad, 598 F.3d at 1354-55 (“Regardless whether the asserted claims recite a compound, Ariad still must describe some way of performing the claimed methods... the specification must demonstrate that Ariad possessed the claimed methods by sufficiently disclosing molecules capable of reducing NF-kB activity so as to ‘satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed.’”) (internal citation omitted); see also Univ. of Rochester v. G.D. Searle& Co., Inc., 358 F.3d916,918 (Fed.Cir.2004) (applying the same analysis to assess written description for claims to a “method for selectively inhibiting” a particular enzyme by administering a functionally defined compound, i.e., a “non-steroidal compound that selectively inhibits activity” of the gene product for that enzyme).
In regards to claims to a product defined by function, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 at1568 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genera. That is, the specification provides neither a representative number of members of the genera nor does it provide a description of structural features that are common to the genera so that one of skill in the art can ‘visualize or recognize’ the members of the genera. “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The functional requirements of the claimed proteins is the sort of wish list of properties which fails to satisfy the written description requirement because proteins with those properties have not been adequately described. see Centocor, 636 F.3d at 1352. The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.”Ariad Pharmaceuticals, Inc. v. EliLilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
Since the disclosure fails to describe common attributes or characteristics that adequately identify members of the genera, and because the genera are highly variant, the disclosure of V33E FmIH, F63E FmIH, and L32E FmIH are insufficient to describe the genera. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genera as broadly claimed.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, even though Applicant may propose methods of screening for possible members of the genera, the skilled artisan cannot envision the detailed chemical structure of the encompassed genera, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolation. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. See Ariad, 94 USPQ2d at 1161; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 2, 4, 5, 12-15, 17, and 18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kisiela et al (PNAS, 2013, 110(47): 19089-19094).
Kisiela et al teaches FimH-mediated adhesion is critical for E. coli strains to colonize and establish infection (left column on page 19089, in particular). Kisiela et al further teaches generating an allosteric cell attachment bacterial adhesion protein, E. coli FimH, in a functionally inactive (low affinity) conformation comprising substitution of hydrophobic and aliphatic V27 and L34 with charged cysteines (left column on page 19090, in particular).
Kisiela et al further teaches using the functionally inactive V27C/L34C FimH constructs to induce adhesion-blocking antibodies in an effort to generate a product that prevents attachment of microbial pathogen to attach to host cells (left column on page 19089 and page 19090, in particular).
Claim Rejections - 35 USC § 102
Claim(s) 1-7, 12-18, and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rodriguez et al (JBC, 2013, 288(33): 24128-24139; 3/20/24 IDS).
Rodriguez et al teaches generating an allosteric cell attachment bacterial adhesion protein, E. coli FimH, in a functionally inactive (low affinity) conformation comprising V67k or V27C/L34C (left column on page 24135, in particular). Rodriguez et al teaches generating an allosteric cell attachment bacterial adhesion protein, E. coli FimH, in a functionally active (high affinity) conformation comprising L68V (left column on page 24134 and Fig. 4, in particular).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 2, 4, 5, 9-15, 17, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kisiela et al (PNAS, 2013, 110(47): 19089-19094) as applied to claims 1, 2, 4, 5, 12-15, 17, and 18 above, and further in view of Leenaars et al (ILAR Journal, 2005, 46(3): 269-279) and Newcombe et al (Journal of Chromatography B, 2007, 848: 2-7).
Teachings of Kisiela et al are discussed above.
Kisiela et al does not specifically state the adhesion-blocking antibodies of Kisiela et al were generated by forming a composition comprising the V27C/L34C FimH construct and an immunogen, administering the composition to a subject, obtaining a blood sample from the subject, and isolating the adhesion-blocking antibodies from the blood sample. However, these deficiencies are made up in the teachings of Leenaars et al and Newcombe et al.
Leenaars et al teaches antibodies against an antigen are generated by injecting antigen or antigen/adjuvant mixtures to subjects to induce an effective antibody response and obtain the antibodies by collecting blood (paragraph spanning columns of page 269, in particular). Leenaars et al further teaches the adjuvant of antigen/agent mixtures functions as a stimulus to induce an effective immune response (left column on page 271, in particular).
Newcombe et al teaches that antibodies are purified from serum of subjects from which the antibodies are generated (Fig 1, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to generate adhesion-blocking antibodies of Kisiela et al to inhibit E. Coli infection by injecting a composition comprising V27C/L34C FimH of Kisiela et al or V27C/L34C FimH /adjuvant mixtures to subjects to induce an effective antibody response against the V27C/L34C FimH antigen of Kisiela et al and obtain the antibodies by collecting blood from the subjects and purifying the antibodies from serum of the blood because Kisiela et al teaches FimH-mediated adhesion is critical for E. coli strains to colonize and establish infection (left column on page 19089, in particular), Leenaars et al teaches antibodies against an antigen are generated by injecting antigen or antigen/adjuvant mixtures to subjects to induce an effective antibody response and obtain the antibodies by collecting blood (paragraph spanning columns of page 269, in particular), Leenaars et al teaches the adjuvant of antigen/agent mixtures functions as a stimulus to induce an effective immune response (left column on page 271, in particular), Newcombe et al teaches that antibodies are purified from serum of subjects from which the antibodies are generated (Fig 1, in particular), and one of skill in the art would recognize serum is a component of blood. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Conclusion
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/SEAN E AEDER/Primary Examiner, Art Unit 1642