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 1-8 are pending and currently under consideration.
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 1-8 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 a genus of human monoclonal antibodies that specifically binds to human HMGB1 that treat or prevent frontotemporal lobar degeneration (FTLD) when administered to a subject. However, the written description in this case does not set-forth any human monoclonal antibodies that specifically binds to human HMGB1 that prevent frontotemporal lobar degeneration (FTLD) when administered to a subject. Further, the specification only sets-forth an antibody comprising a heavy chain comprising instant SEQ ID NO:9 and a light chain comprising SEQ ID NO:10 (“antibody #129”) as an example of a human monoclonal antibody that specifically binds to human HMGB1 that appears to treat frontotemporal lobar degeneration (FTLD) when administered to a subject that has FTLD (see Tables 1-2 and pages 42-48, in particular). The specification does not disclose, and the art does not teach, the genus as broadly encompassed in the claims.
The specification only discloses an antibody comprising a heavy chain comprising instant SEQ ID NO:9 and a light chain comprising SEQ ID NO:10 (“antibody #129”) as an example of a human monoclonal antibody that specifically binds to human HMGB1 that appears to treat frontotemporal lobar degeneration (FTLD) when administered to a subject that has FTLD (see Tables 1-2 and pages 42-48, in particular). 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 genus. That is, the specification provides neither a representative number of human antibodies that encompass the genus nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. “[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. Further, in view of Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) and the Office’s February 2018 memo clarifying written description guidance for claims drawn to antibodies, the 2008 Written Description Training Materials are outdated and should not be relied upon as reflecting the current state of law regarding 35 U.S.C. 112. Further, a “newly characterized antigen” test flouts basic legal principles of the written description requirement (Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017)). Adequate written description of a newly characterized antigen alone is not considered adequate written description of a claimed antibody to that newly characterized antigen. Where an antibody binds to an antigen tells one nothing about the structure of any other antibody. Also, see the Board’s decision in Appeal 2017-010877 (claims to “A monoclonal antibody that binds a conformational epitope formed by amino acids 42-66 of SEQ ID NO:1”).
The functional requirements of the claimed antibodies is the sort of wish list of properties which fails to satisfy the written description requirement because “antibodies with those properties have not been adequately described.” 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 genus, and because the genus is highly variant, the disclosure is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus 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 genus, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus, 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 § 112
Claims 1-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of treat a subject with frontotemporal lobar degeneration (FTLD) comprising administering to the subject a human monoclonal antibody that binds to human HMGB1 wherein the human monoclonal antibody comprises a heavy chain comprising instant SEQ ID NO:9 and a light chain comprising SEQ ID NO:10, does not reasonably provide enablement for a method of treating or preventing FTLD comprising administering to a subject just any human monoclonal antibody that specifically binds to human HMGB1 and comprises sequences of six CDRs wherein the six CDRs comprise SEQ ID NOs: 1-6 or any amino sequences in which one or more amino acids are substituted, deleted, added, and/or inserted in SEQ ID NOs: 1-6. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to perform the claimed method commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in Ex parte Forman, 230 USPQ 546 (BPAI 1986). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability or unpredictability of the art, the breadth of the claims, and the quantity of experimentation which would be required in order to practice the invention as claimed.
The instant claims are broadly drawn to treating or preventing FTLD comprising administering to a subject just any human monoclonal antibody that specifically binds to human HMGB1 and comprises sequence of six CDRs wherein the six CDRs comprise SEQ ID NOs: 1-6 or any amino sequences in which one or more amino acids are substituted, deleted, added, and/or inserted in SEQ ID NOs: 1-6. This includes highly unpredictable prophylactic methods of preventing FTLD. It is further noted that recited SEQ ID NOs in claim 1 (which permits any amount of substitutions, deletions, additions, and insertions in recited CDR sequences) provide no limitation on sequences of CDRs (binding domains) of antibodies encompassed by the claims.
This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
Reasonable guidance with respect to preventing any disease (not just FTLD) relies on quantitative analysis from defined populations which have been successfully pre-screened and are predisposed to said disorder. This type of data might be derived from widespread genetic analysis, cancer clusters, or family histories. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical disease and link those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent.
The specification only sets-forth an antibody comprising a heavy chain comprising instant SEQ ID NO:9 and a light chain comprising SEQ ID NO:10 (“antibody #129”) as an example of a human monoclonal antibody that specifically binds to human HMGB1 that appears to treat frontotemporal lobar degeneration (FTLD) when administered to a subject (see Tables 1-2 and pages 42-48, in particular). The specification does not disclose, and the art does not teach, the any other human monoclonal antibody that specifically binds to human HMGB1 that treats FTLD. Further, the specification does not demonstrate any human monoclonal antibodies that specifically binds to human HMGB1 that prevent FTLD when administered to a subject.
One cannot extrapolate the teachings of the specification to the scope of the claims because the claims are broadly drawn to drawn to treating or preventing FTLD comprising administering to a subject just any human monoclonal antibody that specifically binds to human HMGB1 and comprises six CDRs wherein the six CDRs comprise SEQ ID NOs: 1-6 or any amino sequences in which one or more amino acids are substituted, deleted, added, and/or inserted in SEQ ID NOs: 1-6, and Applicant has not enabled said method because (i) the specification has only adequately describe a single antibody encompassed by the claims that treats FTLD, (ii) the specification has not adequately describe any antibody encompassed by the claims that prevents FTLD, and (iii) undue (and unreasonable) experimentation would be required to identify other antibodies encompassed by the claims that treat and prevent FTLD in order to perform the method as broadly claimed.
Further, similar to claims at issue in Amgen Inc. v Sanofi, the instant specification does not enable the full scope of the claims. The instant specification, in view of the prior art, does not teach one of skill the recited genus of antibodies to perform claimed methods.
In view of the teachings above and the lack of guidance, workable examples and or exemplification in the specification, it would require undue experimentation by one of skill in the art to perform the method as claimed.
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 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lundbäck et al (Hepatology, 2016, 64(5): 1699-1710).
Figure 2 of Lundbäck et al teaches a method comprising administering anti-HMGB1 antibody h2G7, which is a monoclonal humanized antibody (a “humanized” monoclonal antibody of Lundbäck et al is a type of “human” monoclonal antibody, as defined by the specification at [0049] spanning pages 22-23) to a subject (equivalent to a subject “in need of prevention” of frontotemporal lobar degeneration) that appears to specifically bind human HMGB1 (note first four lines of the right column on page 1702 stating that the parent antibody of h2G7 binds amino acids 53-63 within box A domain of human HMGB1). h2G7, along with every other imaginable antibody, comprises sequences of six CDRs wherein the six CDRs comprise SEQ ID NOs: 1-6 or any amino sequences in which one or more amino acids are substituted, deleted, added, and/or inserted in SEQ ID NOs: 1-6.
While Lundbäck et al does not specifically demonstrate administered h2G7 prevented FTLD in the subjects, the method of Lundbäck et al appears to be the same as claimed because h2G7 is a monoclonal humanized antibody that appears to bind human HMGB1 and, along with every other imaginable antibody, comprises sequences of six CDRs wherein the six CDRs comprise SEQ ID NOs: 1-6 or any amino sequences in which one or more amino acids are substituted, deleted, added, and/or inserted in SEQ ID NOs: 1-6.
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 1-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12319731 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because patent claims 1-6 are drawn to the same human monoclonal antibodies that specifically bind human HMGB1 (note: instant SEQ ID NOs: 7, 8, 9, and 10 are identical to patent SEQ ID NOs: 12, 17, 11, and 16, respectively) and patent claim 7 is drawn to methods of administering the antibodies to subjects. While the patent claims do not specifically recite the administered antibodies “prevent” FTLD in the subjects the patent methods appear to be the same as claimed because the patent methods administer the same antibody as the instant claims to a subject that is equivalent to a subject “in need of prevention” of frontotemporal lobar degeneration.
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/871213 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because copending claims are drawn to the same antibodies as the instant claims and methods of administering the antibodies to the same subjects as the instant claims, including where the administering is to “treat or prevent” FTLD of the instant claims (note: instant SEQ ID NOs: 7, 8, 9, and 10 are identical to copending SEQ ID NOs: 7, 8, 9, and 10), respectively).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/SEAN E AEDER/Primary Examiner, Art Unit 1642