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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/30/2026 has been entered.
Priority
The present application was filed 01/26/2021 and claims benefit under 35 U.S.C. 119(e) to national stage entry of PCT/GB2019/052101, which in turn claims foreign priority to GB1812331.5, filed 07/27/2018.
Status of the Claims
Claims 1, 8-12, 14-15, 22, 27-29, and 31 are pending. Claim 15 is amended and claims 22, 27, and 31 are withdrawn. Claims 1, 8-12, 14-15, and 28-29 are examined below.
Information Disclosure Statement
The information disclosure statement (IDS) filed 05/12/2026 has been considered, initialed, and is attached hereto.
Withdrawn Rejection
As noted in the advisory action (CTAV 06/03/2026), the rejection under 35 U.S.C. 103 is withdrawn due to the amendment of the claims.
Claims 1, 8-12, 14-15, and 28-29 appear to be free of the prior art.
The claims are free of the prior art because, while Davis et al. WO 2015/059487 (of record, PTO-892, 06/26/2025) does teach an enzyme detection kit for detecting the activity of an enzyme capable of cleaving a substrate comprising an indicator molecule, Davis does not teach indicator molecules comprising SEQ ID NO: 11 nor the sequences of the claimed heavy and light chain CDRs (SEQ ID Nos: 1-6) as recited in claims 1 and 15.
The rejection of claims 15 and 28-29 under 35 U.S.C. 112(a) is withdrawn due to the amendment of the claims.
Maintained Rejection
The rejection of claims 1, 8-12, and 14 under 35 U.S.C. 112(a) is maintained and reiterated below.
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, 8-12, and 14 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites “capture molecules capable of binding to the capture site of the indicator molecule”. The specification on page 12, lines 1-5 recites that the indicator molecule and the capture molecule are two halves of a binding pair selected from a list comprising: an antigen – antibody or binding fragment thereof, biotin and avidin, and immunoglobulin and protein A or G, a carbohydrate and a lectin, complementary nucleotide sequences, a ligand and a receptor molecule and others. The claims encompass a large genus of products that may be characterized by substantial variability. Claim 15 does recite the light and heavy chain sequences of the binding molecule, but only in the alternative to the “antibody specific for the de-sialylated form of the peptide”.
Even limited to the limitation of antibodies, such as “capable of biding to the capture site” (claim 1) and “specific for the de-sialylated form of the peptide” (claim 15), the claims encompass a large and highly variable genus. The claims place no limitation on the sequence/structure of the antibodies themselves, and rather define the antibodies only in terms of desired binding properties.
The claim scope is potentially enormous depending on how many of the products that meet the structural requirement would also meet the functional requirements (i.e., binding the capture site of the indicator molecule or binding the de-sialylated derivative of the indicator molecule). Furthermore, the specification fails to disclose sufficient identifying characteristics of the genus (the claimed antibodies), as discussed in more detail below, such that one having ordinary skill in the art can readily visualize the species encompassed by the claimed genus (i.e., what antibodies meeting the structural requirement also exhibit the required functional, namely binding, requirement).
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Regents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., high affinity, neutralization activity, competing with a reference antibody for binding, binding to a certain epitope), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
Along these same lines, a more recent Federal Circuit decision, Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), describes how when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself; not just a description of the sequence to which the antibody binds. Amgen, 872 F.3d at 1378-79.
It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date” (AbbVie, 759 F.3d at 1298, reiterating Enzo Biochem, Inc., 323 F.3d at 964)(emphasis added).
In the present case, however, there is insufficient evidence of such an established structure-function correlation in the case of antibodies that bind the capture site of the indicator molecule or the de-sialylated derivative of the indicator molecule.
A claimed invention may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule defined solely by its ability to perform a function, such as to serve as an antigen recognizing construct, without a known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the biomolecule of interest. See MPEP 2163.
As discussed in the recent case of Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), see page 17:
An adequate written description must contain enough information about the actual makeup of the claimed products—“a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” which may be present in “functional” terminology “when the art has established a correlation between structure and function.” Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. See, e.g., J.A. 1241 (549:5–16) (Appellants’ expert Dr. Eck testifying that knowing “that an antibody binds to a particular amino acid on PCSK9 . . . does not tell you anything at all about the structure of the antibody”); J.A. 1314 (836:9–11) (Appellees’ expert Dr. Petsko being informed of Dr. Eck’s testimony and responding that “[m]y opinion is that [he’s] right”); Centocor, 636 F.3d at 1352 (analogizing the antibody- antigen relationship as searching for a key “on a ring with a million keys on it”) (internal citations and quotation marks omitted).
Amgen Inc. v. Sanofi further notes, pointing to Ariad Pharms., Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed Cir. 2010):
To show invention, a patentee must convey in its disclosure that it “had possession of the claimed subject matter as of the filing date.” Id. at 1350. Demonstrating possession “requires a precise definition” of the invention. Id. To provide this “precise definition” for a claim to a genus, a patentee must disclose “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.” Id. Amgen at pages 7-8.
In the present case it is also noted that the claims are not limited to any particular molecule, rather the specification recites antigen – antibody or binding fragment thereof, biotin and avidin, and immunoglobulin and protein A or G, a carbohydrate and a lectin, complementary nucleotide sequences, a ligand and a receptor molecule and others and even if limited to an antibody for example, the claims are not limited to any particular epitope of a specific peptide. For example, the claims are not limited to any particular epitope sequence to which the antibody binds, and rather broadly encompass that the antibodies bind the capture site of the indicator molecule or the de-sialylated derivative of the indicator molecule. Nonetheless, even if limited to a particular antigen structure, the art recognizes that structure (of a particular antigen) is not necessarily a reliable indicator of function, so even if the claim was reciting a particular antigen sequence to which the antibody binds, there still may be insufficient written description to support the entire genus as claimed.
Recent court cases have indicated that recitation of an antibody which has specific functional properties in the absence of knowledge of the antibody sequences that give rise to said functional properties do not satisfy the requirements for written description. See AbbVie Deutschland GmbH v. Janssen Biotech. Inc. as well as Amgen v. Sanofi, as discussed above. Indeed, in Amgen the court indicates that that it is improper to allow patentees to claim antibodies by describing something that is not the invention, i.e. the antigen, as knowledge of the chemical structure of an antigen does not give the required kind of structure-identifying information about the corresponding antibodies, with the antibody-antigen relationship being analogized as a search for a key on a ring with a million keys on it.
The specification, in disclosing only one species of antibody specific for the de-sialylated form of the peptide, at best describes plans for making additional antibodies/ binding agents and then identifying those that satisfy claim limitations, but a mere “wish or plan” for obtaining the claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011).
The teachings of Harlow et al. (Antibodies, A Laboratory Manual, Cold Spring Harbor laboratory, 1988, pages 25-26 and 37-59, cited herewith; PTO-892 06/26/2025) which describe how the steps of the humoral immune response to an immunogen are dependent on APC, T-cell and B-cell recognition and processing of the immunogen in ways well known in the art to be highly unpredictable and heavily influenced by the particular immunogen and the specifics of the immunization protocol. Harlow et al. teach that even small changes in structure, such as loss of a single hydrogen bond, can profoundly affect antibody-antigen interaction (p. 25, last paragraph to page 26, second paragraph).
The principles laid out in Harlow are further illustrated in the teachings of Edwards et al. ("The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BLyS" J. Mol. Biol. (2003) 334, 103–118, DOI: 10.1016/j.jmb.2003.09.054; PTO-892 06/26/2025), which shows the immense combinatorial flexibility and capacity of the human antibody repertoire to generate binding sites to an individual protein antigen, the B-lymphocyte growth factor known as “BLyS” (see entire document). Edwards describes in detail how the breadth of antibody structures against a given immunogen can be influenced by the immunization and/or selection methods (see Discussion Section).
As yet another example to illustrate the potential scope of the genus of antibodies encompassed by the instant claims, consider the teachings of Meyer et al. (“New Insights in Type I and II CD20 Antibody Mechanisms-Of-Action With a Panel of Novel CD20 Antibodies”, British Journal of Haematology, 2018, 180, 808–820, |https://doi.org/10.1111/bjh.15132; PTO-892 06/26/2025). Meyer describes the core binding region of the well-known anti-CD20 antibody rituximab corresponds to amino acid residues 170ANPS173, wherein N171 is the key residue for binding. By contrast, the OBZ and B1 anti-CD20 antibodies share an overlapping epitope with rituximab (170ANPSEKNSP178); however, in contrast to rituximab residues at positions 176–178 contribute the most to binding (see page 809, left col., 2nd full paragraph). Meyer also described the production and characterization of a panel of new anti-CD20 antibodies which were shown to bind epitopes contained within or nearby the rituximab 170ANPS173 epitope but to bind to different residues than rituximab binds in this region (see page 811, “New CD20 mAbs with overlapping, but distinct epitopes,” see also page 815-16 bridging paragraph).
More particularly, Meyer teaches the newly created anti-CD20 mAbs m1 and m2 were found to bind within but also in the vicinity of the rituximab binding site (m1 and m2) and elsewhere (m2):
“detailed epitope mapping was performed for both mIgG2c-CD20 mAbs m1 and m2, by using PepScan technology. We identified the critical residues of m1 to be 168EPANPSEK175 by using linear (Figure S2A) and circular (Fig 2C, left) peptides with a positional amino acid scan covering the larger extracellular loop. Also for m2, a signal decrease below the WT binding signal occurred within the 168EPANPSEK175 sequence motif but the binding signal to the linear (Figure S2B) and circular (Fig 2C, right) peptide was rather low. This suggests that the epitope of both mAbs is located on the larger loop in the same region, however their binding characteristics are different. The data suggests that m1 binds a linear epitope, whereas m2 binds to a conformational epitope.” (see ibid). Moreover, while these antibodies bind within or nearby the rituximab 170ANPS173 epitope they do so with heavy and light chain CDRs non-homologous to those of rituximab.
The specification fails to provide adequate written description for the genus of antibodies claimed, as the antibodies are described only in terms of desired function properties and not in terms of common structure or other relevant identifying characteristics to define the genus and there is no apparent structure-function correlation which would allow one to readily visualize what species would and would not be encompassed by the claimed invention. The specification does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
Allowable Subject Matter
Claims 15, 28 and 29 are allowable.
Response to Arguments
Applicant's arguments filed 06/30/2026 have been fully considered but they are not persuasive.
Applicant argues, starting on page 8, that immobilization of molecules using capture reagents is widely used in the biological sciences and may be achieved by a variety of methods which were well known at the filing date of the present application and that for this reason alone, a person of ordinary skill would reasonably conclude that the inventor had possession of the claimed invention. Applicant further argues that the application as filed provides a representative number of species, such as biotin and streptavidin in an example as well as immunoglobulin and a protein A or G, a carbohydrate and a lectin, or xyloglucan and cellulose fibers. Further, applicant argues, the genus of capture molecules are defined functionally because they are not the essential elements required for the detection of cleavage activity of a sialidase enzyme but rather merely used to immobilize the indicator molecule and restricting the capture molecules would be unduly limiting in view of the inventive contribution. Applicant further argues that the Office’s concern regarding capture molecules appears to conflate the written description requirements applicable to novel antibodies with those applicable to conventional immobilization reagents and that the written description requirement is not applied in the context of the particular invention and state of the knowledge.
Applicant argues that the capture molecules recited in claim 1 are not antibodies with novel binding specificities but rather well-known reagents used to immobilize the indicator molecule at the capture zone.
This argument is not persuasive.
Claim 1 currently recites a capture molecule with a specific binding property, namely a “capture molecule capable of binding to the capture site […] irrespective of whether or not the indicator molecule has been cleaved” and as such defines the molecule by what it binds rather than what it is. Regarding the argument that the specification describes various possible binding mechanisms, applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Further, the general examples of possible binding mechanisms provided in the specification do not recite a capture molecule that has the claimed specific binding property.
For all the reasons above, the arguments are not persuasive.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEFANIE J KIRWIN whose telephone number is (571)272-6574. The examiner can normally be reached Monday - Thursday 7.30 - 4 pm.
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/STEFANIE J. KIRWIN/Examiner, Art Unit 1677
/Soren Harward/Primary Examiner, TC 1600
