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 .
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 (i.e., changing from AIA to pre-AIA ) 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.
Priority
The present application is filed as a divisional of application serial number 16/324,878, filed 02/11/19 (US Patent No. 11,680948). Application 16/324,878 was filed as a proper National Stage (371) entry of PCT Application No. PCT/US2017/046499, filed 08/11/2017, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/374,217, filed 08/12/2016.
Information Disclosure Statement
Information disclosure statement (IDS) filed 08/16/2023 is considered, initialed and is attached hereto.
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 5 and 6 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. See MPEP 2163.
Claims 5 and 6 recite limitations intended to further limit the antibody of claim 3 (the antibody conjugated to the detection reagent). See at claim 5, reciting “the antibody specific for natalizumab binds natalizumab at the variable region. Similarly claim 6 recites “the antibody specific for natalizumab binds natalizumab at the constant region”. Each of these claims is directed to a structurally distinct antibody, the antibodies only described in terms of their functional ability (i.e., the claims refer to specific binding as a way to limit/identify the claimed antibody) rather than structure specific to the antibody itself. As such, the claims encompass an extremely large and variable genus of antibodies for claim 5 and also for claim 6, which may be characterized by significant variability in terms of structure, the claims merely limited in terms of what they bind (the claims recite no limiting or identifiable structure specific to each genus itself).
The MPEP states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406). In the present case, the specification further fails to provide a representative number of examples such to provide a structure-function correlation that would allow one to visualize what species would meet the functional (binding) requirements.
Regarding Applicant’s originally filed disclosure, at Example 1 (using Veritope™ peptide based ELISA, not a test device as recited at claim 1 of the present claims), Applicant references a detection antibody that is an HRP-conjugated mouse monoclonal anti-human IgG4 Fc antibody. See also at Example 3 (example for validation of mimetope specificity and assay performance, also not describing a test device as recited by the claimed invention), Applicant describes the use of a detection antibody that is aa goat-anti-human IgG-Fc antibody conjugated to HRP.
Example 4 of the originally filed specification is directed to a test device consistent with the present claims (see para [0073], referring to a device shown in Figure 7, which has structures as presently claimed). Para [0073] describes the use of gold conjugate mimetope.
None of the working examples in the originally filed specification describe sufficient exemplary representative species such to support Applicant was in possession of each of the claimed genus as claimed.
The potential number of species that would be encompassed by each genus is nearly limitless, and Applicant’s originally filed specification does not provide sufficient description such to convey possession of every possible species encompassed by each.
“[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. Reagents 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 and established structure-function correlation in the case of antibodies that bind natalizumab at the variable versus constant regions.
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).
In the instant claims, the recited antibodies are only described in terms of what they bind, and where they bind that target (natalizumab, at the variable or constant regions, claims 5 and 6), which as discussed in the case of Amgen Inc. v. Sanofi, does not convey any information specific to the structure of such antibodies themselves.
The teachings of Harlow et al. (Antibodies, A Laboratory Manual, Cold Spring Harbor laboratory, 1988, pages 25-26 and 37-59, IDS entered 08/16/2023) 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), 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). 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.
Thus, even if multiple different antibodies bind epitopes within the same small region of a given polypeptide it is not uncommon for said antibodies to bind to different amino acids even within said small region and for said antibodies to have structurally dissimilar CDRs (i.e., distinct structures specific to the antibodies themselves).
One cannot visualize or recognize the identities of the members of each genus that exhibit this functional property (binds to the particular region of the targeted antibody). The applicant was not in possession of all antibodies capable of binding natalizumab as claimed (the variable region and at the constant region). Additionally, the characteristics defining the genus of antibodies that bind natalizumab are unknown as this only sets forth what the antibodies do and not what they are.
There is no disclosed partial structure or other common structural features, common to the members of the genus, which are responsible for conferring the desired function.
For these reasons, the specification does not convey to one skilled in the relevant art that the inventor(s) were in possession of the claimed invention.
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 2, 4, 7-14, 16 and 19 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.
Claim 2 recites “wherein the conjugate pad comprises a detection reagent conjugated to the peptide in step (c)”. The limitations of claim 2 are indefinite as they refer to “step (c)”, however, claim 1 is a product invention, not a method claim. As a result, there is no “step (c)”, rather (c) at claim 1 is directed to a structure, namely “a test membrane comprising a first test line comprising a peptide consisting of any of SEQ ID Nos: 1, 2, 4, 13, 16 and 18-23”. Further, because claim 1 (c) refers to a structure that comprises a test line at a test membrane, the claim is indefinite because it is not clear how “detection reagent” at the “conjugate pad” can also simultaneously be at and “conjugated to” peptide that is in a separate position at the test line. It is not clear if “the peptide in step (c)” (recited at claim 2) is referring to the peptide that is at the test line of the device, or rather if the claim is referring to additional peptide that is the same as the peptide at the test line, but which is provided at the conjugate pad conjugated with detection reagent, since “the peptide in step (c)” appears to be specific to peptide at the test line of claim 1.
See similarly claims 4 and 7 also refer to “step (c)”, and as such is rejected for the reasons as discussed above (the claims are not directed to method claims).
Claim 4 recites “wherein the conjugate pad comprises a detection reagent conjugated to: the peptide in step (c); and an antibody specific for natalizumab”, see as discussed above, the conjugate pad and the test line comprising the peptide (referring to c at claim 1) are recited as separately located structures on the test device (claim 1). As a result, the claim language is indefinite because it is not readily clear how the detection reagent can be simultaneously conjugated to the peptide at the test line and located at the detection pad (two distinct positions at one time). It is not clear if “the peptide in step (c)” is referring to the peptide that is at the test line of the device, or rather if the claim is referring to additional peptide, that is the same as the peptide at the test line, but which is provided at the conjugate pad conjugated with detection reagent.
Claim 9 recites, in reference to the antibody of the sample, “wherein the antibody is free, circulating natalizumab and not complexed to a protein prior to step (b)”, the claim is indefinite because claim 1 is not directed to a method, but rather a product, as such the claims do not include a “step (b)”. The claim is indefinite because it is not clear what “step (b)” is referencing.
Claim 10 recites “wherein the first test line measures a bivalent form of the antibody”, the claimed invention is directed to a product, namely a test device. It is not clear what additional limiting structure the limitations of dependent claim 10 further apply to the test device of claim 1, other than those which naturally follow from a peptide as claimed at claim 1. As a result, the claim is indefinite because it is not clear how the claim is further limiting, for example it is unclear if it is intended as suggesting/implying additional structure responsible for the recited functional ability of measuring a bivalent form.
Similarly, claim 11 recites “wherein the second test line measures both bivalent and monovalent forms of the antibody”, claim 11 depends from claim 7 which recites the test membrane further comprises a second test line comprising an antibody specific for the peptide. The claim is indefinite because it does not clearly recite additional structure specific to the second test line that would be responsible for/necessarily detect both monovalent and bivalent forms of the antibody.
Claim 12 recites “The test device if claim 1, wherein the test membrane comprises Western blot analysis, dot blot analysis, flow cytometry, enzyme-linked immunosorbent assay (ELISA), lateral flow immunoassay, radioimmunoassay (RIA), competitive immunoassay, dual antibody sandwich assay, chemiluminescent assay, bioluminescent assay, fluorescent assay or agglutination assay”, the limitations of claim 12 fail to clearly recite or imply any additional specific structure to the test device described at claim 1. For example, each of those assays listed read as specific types of methods, and the claimed invention is a product. As such, the claim is indefinite because it is not clear what additional limiting structure the limitations of claim 12 impose on the test device of claim 1.
Regarding claims 13 and 14, claim 13 recites “the test line comprises a dual antibody sandwich assay”, and claim 14 recites “the second test line comprises a competitive immunoassay”, these limitations do not appear to further describe any particular structure. Rather, the language is confusing because rather than further describing/limiting structure, the limitations read as methods to be performed at these structural positions. As a result, the language is indefinite because it is not clear how these limitations further limit the structure of the claimed test device.
Further, regarding claim 13, the limitations “dual antibody sandwich immunoassay” is considered indefinite claim language (even when considered directed to the intended use of the claimed test device), because claim 13 depends from claim 1 and claim recites that the first test line comprises peptide as claimed. As a result, it is not clear how a dual antibody sandwich assay is to be performed at claim 13 given that a dual antibody sandwich assay suggests two antibodies that sandwich an analyte/antigen (i.e., a capture antibody and a detection antibody), and since claim 1 already recites peptide at the test line.
Similarly, claim 19 is indefinite because it is not readily apparent what additional structure/structural feature these limitations impose on the claimed test device, since the limitations of claim 19 appear to further limit the sample (which the test device is intended to be used on) rather than limiting the test device itself. The sample is not recited as part of the claimed test device at claim 1.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 17-19 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 17-19 recite limitations specific to the sample, which the sample is not a structure/structural component of the claimed test device. As such, these claims fail to further limit the claimed subject matter (the claimed test device of claim 1). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 3, 9, 10, 12 and 15-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/404,4651 (reference application) in view of Hammond et al. WO03/089922A1, Chaikof et al., WO2014/070865A1 and Arroyo-Ornelas et al. (2012). Immune Diagnosis of Tuberculosis Through Novel Technologies. 10.5772/31421. (16 pages).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons:
Copending ‘461 at claim 1 recites compositions and methods comprising the peptide as presently claimed (see for example, ‘461 recites the peptide of present claim 1 SEQ ID NO. 1 except for the tag GGG). ‘461 further at claim 4 recite the peptide attached at a solid support, see specifically at claim 7 the method performed as a lateral flow immunoassay.
As such, ‘461 is teaching a method using a test device substantially similar (comprising peptide immobilized at a solid support, performed as a lateral flow immunoassay thereby supporting the methods comprising peptide immobilized as a lateral flow assay device). However, ‘461 fails to teach a lateral flow assay device comprising a sample pad for receiving sample comprising an antibody (or fragment), a conjugate pad, and a test membrane comprising a first test line comprising the peptide. Further, as noted above, the peptide of the copending is absent the triglycine peptide.
However, see for example, Hammond et al., it is a known technique in the prior art to conjugate ligands to a surface of a support by way of a linker, for example a glycine linker (para [0017]). See also Chaikof et al., para [0083], which reports for example the peptidic glycine linker, GGG (triglycine).
Arroyo-Ornelas et al. teach an example of a lateral flow assay device for detecting a targeted analyte that is an antibody, the device comprising a sample pad for receiving sample, a conjugate pad containing gold labeled conjugate, and a test line, comprising antigen for the antibody (see for example page 390, Figure 5, peptide is immobilized on a solid support that is a lateral flow assay test). See Arroyo-Ornelas teach lateral flow immunochromatography platforms as one of the most advantageous platforms for antigen-antibody reaction (page 289, para 3).
When providing the assay for the invention of ‘461 as a lateral flow assay, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the solid support of ‘461 to provide it as a lateral flow assay strip, as taught by for example Arroyo- Ornelas (namely a stirp comprising a sample pad, a conjugate pad and a test line comprising immobilized peptide). One having ordinary skill would have been motivated to provide a test device such as those taught by Arroyo- Ornelas because ‘461 specifically discloses the assay can be performed as a lateral flow assay, which suggests the use of such a device (as that of Arroyo- Ornelas), such devices having a known structure such as that taught by Arroyo- Ornelas, these devices recognized in the art as one of the most advantageous platforms for antigen-antibody reaction.
Even further, one having ordinary skill in the art would have a reasonable expectation of success given that ‘461 specifically discloses lateral flow assay format as an assay format for detection of their targeted analyte, and further because these types of devices were known and recognized in the art for detecting analyte that is an antibody, using immobilized peptide for said antibody at their test line (see as is additionally supported by, for example, Arroyo- Ornelas).
As noted above, the claimed peptide differs from that recited at the copending application merely by the triglycine tag (GGG) at the N-terminal region of the peptide, however, it would have been obvious to one having ordinary skill in the art to have modified the peptide with GGG as an obvious matter of applying a known technique, specifically, the prior art recognized using glycine linker molecules (such as GGG) in order to immobilize peptides to solid support substrates (see for example, Hammond et al. and Chaikof et al., cited in detail above). Based on the cited art, the peptide of ‘461 with the triglycine peptidic linker is considered to be an obvious modification for attachment of the peptide to solid support substrates, one having ordinary skill in the art would have a reasonable expectation of success using a known technique for its art recognized, intended purpose (in this case, for attaching peptide to a solid support).
Regarding claims 3, the combination of the cited art is teaching immobilized peptide of ‘416, and as such is teaching a device for the detection of natalizumab. It would be further obvious that the detection reagent of the combined cited art be modified to be specific for natalizumab as well for the reasons discussed in detail above.
Regarding claim 9, the limitations of claim 9 are directed to the sample which does not further limit the claimed test device. The device as taught by the combined cited prior art is considered capable of detection free circulating antibody that is natalizumab in a sample (the test line of the cited prior art would be expected capable of this action).
Regarding claim 10, the limitation of claim 10 also fail to further limit the test line (the test line comprises the claimed peptide). See as cited above, the combination of the cited prior art is teaching a test device comprising the same test line, as such it would similarly be capable of the same function, namely measuring bivalent form of the antibody target.
Regarding claim 12, the combination of the cited art is teaching a lateral flow assay test device (capable of lateral flow immunoassay).
Regarding claim 15, see further Arroyo-Ornelas et al. as cited above, showing a control line. It would have been further obvious to one having ordinary skill, when providing ‘461 as a lateral flow device (as is recited by ‘461), to further provide a control line for binding/detecting conjugate as an obvious matter of applying a known technique to a known device. ‘461 specifically provide that their assay can be performed as a lateral flow assay, and Arroyo-Ornelas demonstrate such test device (for lateral flow assay) with a specific line as a control line for binding conjugate. One having ordinary skill would have found it obvious to provide a control line and the results of the modification would have been predictably the ability to assess whether conjugate properly flowed through the assay device (assay device operated as intended). One having ordinary skill in the art would have a reasonable expectation of success applying a known technique to a known device intended for lateral flow assay (considering ‘461 does recite the assay can be a lateral flow assay).
Regarding claim 16, see also Arroyo-Ornelas teach providing colloidal gold as the detectable label for lateral flow assay (Figure 5). It would have been prima facie obvious to one having ordinary skill to use a known label for its art recognized purpose, one having ordinary skill having a reasonable expectation of success employing a known material for its intended purpose (as a detectable label for latera flow assay device).
Regarding claims 17-19, the limitations of claim 17 are specific to the sample which is not a recited structure specific to the claimed device. The device of the cited art would be expected capable of being used on a sample that is biological fluid, see ‘461 sample that is a biological fluid (copending claims 9, 10 and 12).
Regarding claim 20, see copending ‘461 at claim 7 (lateral flow assay device).
Claims 2 and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/404,4651 (reference application) in view of Hammond et al., Chaikof et al., and Arroyo-Ornelas et al, as applied to claim 1 above, and further in view of Tseng et al., US PG Pub No. 2005/0037338A1.
‘461 and the cited art teach a test device substantially as claimed, however fail to teach the conjugate pad comprises a detection reagent conjugated to the peptide in step (c) (see rejection set forth in detail above; in the interest of compact prosecution the claim limitation is interpreted as referring to peptide that is the same peptide as immobilized at the first test line).
Tseng also teach an example of a lateral flow assay strip device for the detection of a target that is an antibody (see for example Figures 3 and 4, and claims). Tseng teach providing labeled recombinant antigen at the conjugate pad (para [0049]), the labeled peptide antigen binds with antibody in the sample for capture at the test area (test area containing immobilized unlabeled antigen, and control antibody for capturing unbound labeled antigen).
Alternative to above, it would have been obvious to have provided at the conjugate pad, labeled peptide (same peptide as the unlabeled peptide at the test area), as an obvious matter of a simple substitution of one known immunoassay binding technique for another (using labeled antigen rather than labeled antibody, in order to form a sandwich at the test line to indicate the presence of antibody, see as in Tseng). In particular, the base test device was known in the prior art (lateral flow assay test device for detecting a target that is an antibody), further it was known to rely on either of labeled peptide conjugate or labeled antibody conjugate for detection of the targeted antibody analyte. One having ordinary skill in the art would have a reasonable expectation of success using one in the place of the other as both are expected to result in detection of the targeted antibody.
Claim 5 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/404,4651 (reference application) in view of Hammond et al., Chaikof et al., and Arroyo-Ornelas et al, as applied to claim 1 above, and further in view of Borges et al., US PG Pub No. 2008/0102065A1.
‘461 and the cited art teach a test device substantially as claimed, however fail to teach the detection antibody is an antibody that binds the variable region of natalizumab (claim 5).
Borges et al. teach anti-idiotypic antibodies are known to bind the variable region of another antibody, teaching using such antibodies to detect the presence of a particular antibody in a sample (see para [0228]).
It would have been further prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have provided an anti-idiotypic antibody, that binds the target antibody at the variable region (as in Borges) as the detectable antibody as an obvious matter of applying a known technique, specifically because the prior art teach using such antibodies to detect a particular antibody in a sample (a targeted antibody). One having ordinary skill would have a reasonable expectation using a known technique as it is intended to be used (i.e., Borges teach anti-idiotypic for binding a particular antibody), specifically considering ‘461 is teaching a target that is an antibody.
Claim 6 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/404,4651 (reference application) in view of Hammond et al., Chaikof et al., and Arroyo-Ornelas et al, as applied to claim 1 above, and further in view of Schrier et al., US 6,008,059.
‘461 and the cited art teach a test device substantially as claimed, however fail to teach the detection antibody is an antibody that binds the constant region of natalizumab (claim 6).
However, see Schrier et al. at col. 12, lines 59, to col. 13, line 6, teaches when an analyte is an antibody, using labeled antibody to the antibody analyte that binds to the constant region in order to prevent interference.
It would have been prima facie obvious to one having ordinary skill in the art to have provided detection antibody that targets the constant region in order to prevent possible interference (Schrier et al.). One having ordinary skill would have a reasonable expectation of success because like ‘461, Schrier teach target analyte that is an antibody.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Correspondence
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/ELLEN J MARCSISIN/ Primary Examiner, Art Unit 1677