DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment of 5/26/26 has been entered in full. Claims 1-2, 4-5, 7, 9, 12, 15 and 19 are amended. Claims 13 and 16-17 are canceled. New claims 20 and 21 are added. Claims 1-12, 14-15 and 18-21 are pending.
Applicants' election with traverse of Group I, currently claims 1-3 and 20-21, drawn to a combination of biomarkers comprising COL1A1 and CCN5, was previously acknowledged. Claims 4-12, 14-15 and 18-19 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The elections without traverse of (1) “protein biomarkers/antibodies” as the species of “biomarker structure/means of detection”, and (2) CCL2 as the species of first additional markers, were also previously acknowledged.
Claims 1-3 and 20-21 are under consideration, as they read on the elected species.
Withdrawn Objections and/or Rejections
The following page numbers refer to the previous Office Action (2/23/26).
The objections to the specification at page 3 are withdrawn in view of the amendments to the specification.
All objections and/or rejections of canceled claim 13 are moot.
The objections to claims 1-3 at page 3 are withdrawn in view of the amendments to the claims.
The rejection of claims 1-3 at pages 4-7 under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more is withdrawn in view of the amendments to independent claim 1 that require the combination to also include a first detectably labeled compound that forms a specific complex with COL1A1 and a second detectably labeled compound that forms a specific complex with CCN5.
The rejection of claims 1-3 at pages 8-9 under 35 U.S.C. 102(a)(1) as being anticipated by Goldenberg et al (1996) is withdrawn in view of the amendments to the claims.
New rejections necessitated by Applicants’ amendment
Claim Rejections - 35 USC § 112(b)
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 1-3 and 20-21 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 pre-AIA the applicant regards as the invention.
Claim 1 as amended is directed to a “combination of biomarkers” that comprises COL1A1, CCN5, a first detectably labeled compound that forms a specific complex with COL1A1 and a second detectably labeled compound that forms a specific complex with CCN5. However, only COL1A1 and CCN5 are biomarkers; labeled compounds are not biomarkers. Therefore, the claim is indefinite because it includes two compounds that are not biomarkers as part of a combination of biomarkers. In this regard, the claim could be rendered definite by amending it to recite a “a combination of biomarkers and detectably labeled compounds…”
The remaining claim(s) included in the rejection are dependent claims that depend from one of the claims rejected above, and encompass the same indefinite subject matter.
Claim Rejections - 35 USC § 112(a), written description
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 1-3 and 20-21 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.
Per MPEP 2163, 35 U.S.C. 112(a) requires, “separate and distinct from the enablement requirement”, that the “specification shall contain a written description of the invention…” (Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010)). In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicants are claiming and what Applicants have possession of.
The instant claims are directed to a product; specifically, a combination of biomarkers comprising COL1A1 and CCN5, and as amended, also comprising a first detectably labeled compound that forms a specific complex with COL1A1 and a second detectably labeled compound that forms a specific complex with CCN5.
The term “compound” is not provided with a limiting definition in the specification, and therefore broadly encompasses any type of structure. In the independent claim, the compounds only limited by functionality (forming a specific complex with COL1A1 or CCN5) and are not limited structurally, encompassing any possible structure. The specification envisions that these antagonists include at least antibodies and nucleic acids, e.g., at ¶ 213-214, but the genus broadly encompasses other structures such as peptides, other proteins, small molecules, peptides, carbohydrates, lipids and more. Each of these, such as the antibodies which are the elected species under consideration, is a distinct subgenus that encompasses a group of species, each having the required functionality. The genus “antibody” encompasses a range of monoclonal antibodies, which are each limited to a single defined antibody structure binding to a target antigen.
The prior art recognizes that antibodies bind to epitopes of 5-7 amino acids (Benjamini et al, 1991. Immunology: A Short Course, 2nd edition, page 40 only). The human COL1A1 precursor protein is 1,464 amino acids in length (page 3 of Devos et al, 2023, Int J Mol Sci. 24: 10004; pages 1-33 as printed). Thus, even considering only continuous epitopes, COL1A1 comprises a multitude of different regions of five amino acids that can serve as epitopes (e.g., residues 1-5, 2-6, 3-7, up to residues 1460-1464). The human CCN5 protein (also known as WISP-2) is smaller at 250 amino acids in length (page 534 of Ji et al, 2014. Oncology Reports. 31: 533-539) but still comprises a large number of different regions that can serve as epitopes (e.g., residues 1-5, 2-6, 3-7, up to residues 246-250).
While the general structure of an antibody was well-known in the prior art, it is the structures of the complementarity-determining regions (CDRs) that determine the specificity of a particular antibody and said CDR structures are not predictable based on the epitope to which it binds. Thus, even knowing the structure (CDRs) of one antibody does not allow the skilled artisan to predict the structure of other antibodies that bind to the same epitope or to the other epitopes in the same protein. The relevant art, Ferrara et al (2015. mAbs. 7(1): 32-41) teaches that there is substantial variation in the structure of antibodies that bind to a single protein, on the order of hundreds of different sequences; specifically, see page 36: "The number of different HCDR3s selected against the test antigens ranges from 74 to 460 (Table 3), with the actual number of different antibodies likely to be significantly higher when different VL chains and additional VH mutations are taken into account” (pg 36). Thus, there are at least hundreds of different antibody structures that bind to the COL1A1 protein, and hundreds of other antibody structures that bind to the CCN5 protein.
Thus, the claims are genus claims because they encompass use of subgenus of antibodies having the required functionality, i.e., those binding to COL1A1 and those binding to CCN5 . However, a product defined by function is not in and of itself sufficient to describe the product because it is only an indication of what the product does, rather than what it is; i.e., the specific structure of the product. It is only a definition of a useful result rather than a definition of what achieves that result. Per MPEP 2124, "describing a composition by its function alone typically will not suffice to sufficiently describe the composition". Furthermore, in the instant case the specification does not establish a correlation between structure and function; i.e., the structure of one anti-COL1A1 or one anti-CCN5 antibody does not provide predictability regarding other antibody structures having the same functionality. Furthermore, the decision of the Federal Circuit in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Circ. 2017) held that a claim directed to an antibody requires written description of the antibody itself rather than being satisfied solely by a written description of the antigen to which it binds (the so-called "newly characterized antigen" test). Thus, a description of the target protein (e.g. COL1A1 or CCN5) is not in and of itself sufficient to provide a description of the genus of antibodies binding to said target.
Written description for a genus may also be satisfied through sufficient description of a relevant number of species. This is dependent on whether one of skill in the art would recognize necessary common attributes or features possessed by the members of the genus. Generally, in an unpredictable art, adequate description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. Also, “[w]hen a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)). “[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” (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69).
In support of the subgenus of compounds that are anti-COL1A1 antibodies, the specification does not provide any specific examples of antibody structures (e.g., disclosure of the amino acid sequences of the complementarity-determining regions (CDRs) of the heavy and light chains of the antibody. Likewise, the specification does not provide any specific examples of antibody structures having the ability to bind to CCN5.
Per MPEP 2163, "A "representative number of species" means that the species which are adequately described are representative of the entire 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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). As such, the specification does not provide representative examples of antibodies that binds to COL1A1 or CCN5.
With respect to the broader genus of compounds that form a specific complex with COL1A1 and/or CCN5, the only other examples that are provided are nucleic acid binding compounds, which are predictable based on the sequence of the COL1A1 and CCN5 genes and corresponding transcripts.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), 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” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116).
Therefore, only a combination of biomarkers for preterm delivery before 32 weeks of gestation in a pregnant individual, comprising a COL1A1 nucleic acid, a CCN5 nucleic acid, a first detectably labeled nucleic acid that forms a specific complex with said COLA1A1 nucleic acid, and a second detectably labeled nucleic acid that forms a specific complex with said CCN5 nucleic acid, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112(a). Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (pg 1115).
Note on Prior Art Rejection(s)
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 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.
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.
Claims 1-2 and 20-21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chatterjee-Kishore et al, U.S. Patent Application Publication 20060252045, published 11/9/06. The earliest date to which the instant application claims priority is 10/26/20.
Claim 1 as amended encompasses a combination of biomarkers for preterm delivery before 32 weeks of gestation in a pregnant individual, comprising COL1A1, CCN5, a first detectably labeled compound that forms a specific complex with COL1A1 and a second detectably labeled compound that forms a specific complex with CCN5. The recitation that the biomarkers are “for preterm delivery before 32 weeks of gestation in a pregnant individual” has been considered in the context of the entire claim and is interpreted as an intended use for the method because it does not result in any structural difference between the claimed product and a prior art reference teachings the same product. See MPEP 2111.02. As such, claim 1 as amended encompasses a combination of COL1A1, CCN5, a first detectably labeled compound that forms a specific complex with COL1A1 and a second detectably labeled compound that forms a specific complex with CCN5. The terms “biomarker” and “compound” each encompass nucleic acids, and thus “biomarker” encompasses a nucleic acid transcript in a sample, and “compound” encompasses a probe for detecting said transcript.
The ‘045 publication teaches “a composition comprising a plurality of probes” wherein “the probes comprise nucleic acid sequences that anneal to nucleic acids” (claim 32) and further comprising “probes that anneal to nucleic acid sequences” of group including COL1A and WISP2 (which is another name for CCN5) (claim 37). The specification teaches that these probes are for assaying the gene expression of genes including COL1A and WISP2 (¶ 312-313). The ‘045 publication teaches assays for transcription profiling, including using Taqman (¶ 1039). ‘045 further teaches specific probes and primers for use in Taqman, which include those for COL1A1 and WISP2 (¶ 1040; Table 13). In Taqman, a “variation of fluorescent PCR”, the probe is inherently a “fluorescent probe” (see page 31 of Proudnikov et al, 2003. Journal of Neuroscience Methods. 123: 31-45; cited here solely to support inherency), and thus detectably labeled as required by claim 1. Thus ‘045 teaches a combination of COL1A and CCN5 nucleic acids (which are biomarkers) together with fluorescent (detectably labeled) probes that bind to said nucleic acids. As such, the teachings of ‘045 anticipate claim 1.
Claim 2 encompasses the combination of biomarkers of claim 1 wherein the combination further comprises one or more additional biomarkers selected from a group including IL1RL1 and a detectably labeled compound that forms a specific complex with said biomarker. ‘045 further teaches that the plurality of probes can comprise nucleic acid sequences that anneal to nucleic acid sequences of genes or gene transcripts of Tables 1-5, 11 or 12” (claim 36). IL1RL1 is included in Table 3 (¶ 302) and Table 12 (¶ 1038). As such, the teachings of ‘045 also anticipate claim 2.
Claims 20 and 21 limit the combination of claim 1 (claim 20) or claim 2 (claim 21) to one wherein the labeled compounds are oligonucleotides. The teachings of ‘045 that anticipate parent claims 1 or 2 set forth above are directed to embodiments where the labeled compounds are probes that are oligonucleotides. As such, the teachings of ‘045 also anticipate claims 20 and 21.
Conclusion
No claims are allowed.
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 extension fee 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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) Form at https://www.uspto.gov/patents/uspto-automated-interview-request-air-form.
/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
Prosecution Insights