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 .
Detailed Action
The Amendments and Remarks filed 3/25/26 in response to the Office Action of 10/2/25 are acknowledged and have been entered.
Claim 23 has been added by Applicant.
Claims 1-10, 13, 15, 16, 18, and 21-23 are pending.
Claims 1-10, 13, 15, 16, and 22 have been amended by Applicant.
Claims 1-10, 13, 15, 16, 18, and 21-23 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The following Office Action contains NEW GROUNDS of rejections Necessitated by Amendments.
Rejections Withdrawn
Rejection of claims 4-6 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The rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn.
The rejections of claims under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for lack of enablement are withdrawn.
The rejections under 35 U.S.C. 102(a)(1) are withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 112
Claims 2-3 remain 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: (1) a genus of polypeptides comprising a domain of R-spondin 2 that inhibit R-spondin 2 and/or R-spondin 3 mediated BMP receptor inhibition; (2) a genus of polypeptides comprising a domain of R-spondin 3 that inhibit R-spondin 2 and/or R-spondin 3 mediated BMP receptor inhibition; (3) a genus of polypeptide comprising a domain of BMP receptor that inhibits R-spondin 2 and/or R-spondin 3, a genus of peptide aptamers that inhibits R-spondin 2 and/or R-spondin 3; (4) a genus of polynucleotide aptamers that inhibit R-spondin 2 and/or R-spondin 3 mediated BMP receptor inhibition; (5) a genus of anticalins that inhibit R-spondin 2 and/or R-spondin 3 mediated BMP receptor inhibition; and (6) a genus of Designed Ankyrin Repeat Proteins that that inhibit R-spondin 2 and/or R-spondin 3 mediated BMP receptor inhibition. 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 that encompass 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. 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.
The functional requirements of the claimed members of the genera the sort of wish list of properties which fails to satisfy the written description requirement because members of the genera 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 genera, and because the genera are highly variant, the disclosure of is 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).
Response to Arguments
In the Reply of 3/25/26, Applicant amended the claims to remove “immunoglobulin” language. Applicant further pointed-out support in the specification for RNAi agents (SEQ ID NO:9-11) and gRNAs, inhibitors that are not at issue with this rejection. Applicant further cited the specification as providing “amino acids 144-204 or R-spondin 2” as an example of a TSP1 domain, “amino acids 37-84 of human R-spondin 2” as an example of an FU1 domain, and “amino acids 1-152” as an example of an extracellular domain of BMP receptor 1A. Applicant indicates the rejection should be withdrawn because the claims are limited to molecules that were synthesized, characterized, and validated in the specification. Applicant further argues the claims are not defined by function alone and require precise structural features and specifically defined amino acid domains with exact sequence coordinates that are disclosed and validated in the specification.
The amendments to the claims and the arguments found in the Reply of 3/25/26 have been carefully considered, but are not deemed persuasive. In regards to the citation of specification as providing “amino acids 144-204 or R-spondin 2” as an example of a TSP1 domain, “amino acids 37-84 of human R-spondin 2” as an example of an FU1 domain, and “amino acids 1-152” as an example of an extracellular domain of BMP receptor 1A, a single species of each genus does not adequately describe the genera. Further, the Reply did not point-out any species of the following genera: (1) a genus of polypeptides comprising a domain of R-spondin 3 that inhibit R-spondin 2 and/or R-spondin 3 mediated BMP receptor inhibition; (2) a genus of polynucleotide aptamers that inhibit R-spondin 2 and/or R-spondin 3 mediated BMP receptor inhibition; (3) a genus of anticalins that inhibit R-spondin 2 and/or R-spondin 3 mediated BMP receptor inhibition; and (4) a genus of Designed Ankyrin Repeat Proteins that that inhibit R-spondin 2 and/or R-spondin 3 mediated BMP receptor inhibition.
In regard to the indication the rejection should be withdrawn because the claims are limited to molecules that were synthesized, characterized, and validated in the specification and the claims are not defined by function alone and require precise structural features and specifically defined amino acid domains with exact sequence coordinates that are disclosed and validated in the specification, the examiner disagrees. Claims 2-3 are not limited to molecules or particular sequences that were synthesized, characterized, and validated in the specification. Rather, the claims encompass genera, some asserted to comprise species and others with a single disclosed species, that were not synthesized, characterized, and validated in the specification.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 7, 8, 15, 16, 18, and 21-23 are rejected under 35 U.S.C. 103(a) as being unpatentable over Meng-er et al (Blood, 1988, 72(2): 567-572) in view of Grčević et al (Leukemia Research, 2003, 27, 731-738).
Meng-er et al teaches a method of treating acute promyelocytic leukemia comprising administering all-trans retinoic acid (ATRA) to subjects with acute promyelocytic leukemia (Abstract, in particular). Said subjects are equivalent to those identified as benefiting from treatment with ATRA. Meng-er et al teaches said method further comprising administering to the subject the antiproliferative agent ara-c (left column on page 569, in particular).
Meng-er et does not specifically teach the subjects with acute promyelocytic leukemia include those with leukemia cells that exhibit decreased BMP receptor activity caused by R-spondin 2 and/or R-spondin 3. However, these deficiencies are made up in the teachings of Grčević et al.
Grčević et al teaches BMP receptor expression in bone marrow and peripheral blood samples from patients with acute promyelocytic leukemia before and during treatment with ATRA (Figure 2, in particular). Figure 2 of Grčević et al illustrates some samples of some patients exhibited lower expression levels of some BMP receptors prior to treatment with ATRA as compared to during treatment, including BMP RIA of patient #2, BMP RII of patient #2, and BMP RII of Patient #3. One of skill in the art would recognize acute promyelocytic leukemia cells are found in bone marrow and peripheral blood samples from patients with acute promyelocytic leukemia.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the method of Meng-er et al wherein just any subject with acute promyelocytic leukemia, including subjects with decreased BMP receptor activity caused by any manner, are therapeutically administered ATRA sequentially, or optionally as a combined preparation, in combination with the antiproliferative agent ara-c because Meng-er et al demonstrates subjects with acute promyelocytic leukemia therapeutically benefit from being administered ATRA optionally in combination with the antiproliferative agent ara-c and Grčević et al teaches decreased BMP receptor expression (an indication of reduction BMP receptor activity) in bone marrow and peripheral blood samples from patients with acute promyelocytic leukemia. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Objections
Claims 4-5 are objected to for being dependent upon a rejected claim.
Claim 6 is objected to because of an apparent typographical issue. Claim 6 recites “…of the human BMP receptor 1A.” Because humans are known to contain multiple BMP receptor 1A, it appears Applicant intended the claim to recite “…of human BMP receptor 1A.” Proper correction is required.
Allowable Subject Matter
Claims 9, 10, and 13 are allowed.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/SEAN E AEDER/Primary Examiner, Art Unit 1642
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