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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-10 and the method of measurement species steps (C-1) to (C-3) in the reply filed on 11/10/25 is acknowledged. Currently, claims 1-12 are pending. Claims 3-6 and 11-12 are withdrawn as being directed to non-elected inventions. Accordingly, claims 1-2 and 7-10 are under examination.
Abstract
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The instant abstract utilized implied phrases see “The present invention relates to”. This language should be avoided.
Also, the current abstract is not limited to a single paragraph.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2 and 7-9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas and/or to laws of nature/natural phenomena without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
The is directed to a naturally occurring correlation between the amount of prohaptoglobin and inflammatory bowel disease.
Step 2A, Prong 2
The additional elements of subject a specimen to reduction treatment and using an antibody which is an antibody that specifically binds to an amino acid sequence set forth in SEQ ID NO: 1 does not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
Also, with respect to the recitation “determining that a subject has inflammatory bowel disease by using the prohaptoglobin amount..”. The “determining” statement at best articulates the judicial exception, amounting only to a general instruction to apply or use the judicial exception. This could read on mental activity being performed solely in a practitioner’ head, e.g. A mental appreciation of prohaptoglobin being correlated with inflammatory bowel disease. No active method steps are invoked or clearly required; the “determining” statement does not include any activity that would constitute a practical application, i.e. steps that apply, rely on or use the natural principle in a manner such that the claims amount to significantly more that the natural principal itself.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
Further, the additional elements of the claims are recited with a high level of generality and do not apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. (the active method steps/limitations recited in addition to the judicial exceptions themselves) and do not add significantly more to the judicial exception(s).
As shown by the art below it is well known routine and conventional in the art to subject a specimen to reduction treatment and using an antibody which is an antibody that specifically binds to an amino acid sequence set forth in SEQ ID NO: 1.
It does not appear to be the case that the active steps recited, which are performed in order to gather the data or perform the assay, are steps recited or performed in an unconventional or non-routine way, such to provide an inventive concept under step 2B.
The claimed limitations as currently presented fail to recite limitations that add a feature that is more than well understood, conventional or routine in the field of diagnostics and biochemical assay methodologies.
For all of these reasons, the claims fail to include additional elements that are sufficient to either integrate the judicial exception(s) into practical application(s) thereof, or amount to significantly more than the judicial exception(s).
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 1-2 and 7-10 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.
Regarding the pending claim language of claims 1 and 10, the recited language limits the claims to the use an antibody, however said antibody (is described only in terms of function rather than structure. In particular, the claims may be interpreted as reciting that the antibody, that has certain desired binding properties, namely that it binds to an amino acid sequence SEQ ID NO. 1 of prohaptoglobin.
Regarding claims 1 and 10, the claims encompass a large genus of products that may be characterized by substantial variability; put another way, the claimed genus encompasses many possible species of antibodies, polyclonal antibodies and monoclonal antibodies, each potentially binding one or multiple different fragments as claimed, each characterized by a potentially different antibody sequences. For example, regarding the hybridoma obtained binders, every hybridoma created is going to produce a specific antibody, no two having the same sequence.
Even in the case of binders that are antibodies, the claims encompass a large and highly variable genus as there is no way to visualize what antibodies (which specific antibodies characterized by their own distinct sequences of heavy and light chain regions) would bind the sequence as claimed (the antibodies are described only in terms of what they bind, i.e. the antigens to which they bind, rather than structure specific to the antibodies themselves), and the claims are not limited to any particular antibody producing hybridoma cell line(s). The recited claim language attempts to place limitations on the specific antibodies by what they do, and as a result places no limitations on the sequences/structure of the antibodies themselves (rather defines the antibodies only in terms of desired binding properties, thereby limiting the antibodies of the claimed methods only to those that achieve the desired functions).
The claim scope is potentially enormous depending on how many potential species of the recited genus that meet the structural requirements also meet the functional requirements (the binding described). The originally filed specification fails to disclose any sufficient identifying characteristics specific to the claimed genus of antibodies such to correlate antibody structure with the recited function in a way that would allow one to readily visualize what species of the claimed genus would also exhibit the required functional ability. For example, even in the case of antibodies, one cannot readily visualize the structure(s) of the antibodies that would be encompassed by the recited claims. Without some identified structure, one cannot readily distinguish between those antibodies encompassed by the recited language, from those excluded from the claim. As an example, considering the antibodies: one cannot readily visualize what anti-prohaptoglobin antibodies exhibit the desired binding functions, and bind one of the recited sequence from those known anti-prohaptoglobin antibodies that do not bind this sequence. As presented (referring to claim 1 and 10), the pending claim language would encompass any and all antibodies produced by any hybridoma cell line produced using B-cells from a mammal immunized with prohaptoglobin. Having the sequences as claimed fails to provide sufficient structure specific to the antibodies to allow one to distinguish what species achieve the desired binding functions from those that do not.
The originally filed specification appears to only provide a single antibody which it calls 10-7G2A (e.g. pages 39-41). However, the specification does not provide a structure of this antibody and does not provide a deposit of the antibody. Also, page 41 of the specification it is not possible to measure proHpt with commercially available antibodies.
“[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-a with A2
specificity, can result in a claim that does not meet written description even if the human TNF-a protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. vy. 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, there is insufficient evidence of such an established structure-function correlation in the case of antibodies, for example, that bind the very specific SEQ ID NO. 1.
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 this case, there is no disclosure of any species such to be sufficient to represent the claimed genus of antbodies having the recited functional properties. There is substantial variability in the genus. Since there are a substantial variety of compounds possible within the genus, without disclosure of any common partial structure or
other sufficient identifying characteristics of the genus, the claimed genus is not sufficiently described.
Regarding predictability, without some guidance such as structure-function correlation, it is not possible to visualize the species encompassed by the genus based on recitation of function alone. The teachings of Harlow & Lane (Antibodies, A Laboratory Manual, Cold Spring Harbor laboratory, 1988, pages 25-26 and 37-59) 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/).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).
Lloyd et al. ("Modelling the human immune response: performance of a
10e11 human antibody repertoire against a broad panel of therapeutically relevant antigens”, Protein Engineering, Design and Selection, Volume 22, Issue 3, 1 March 2009, Pages 159-168, https://doi.org/10.1093/protein/gzn058) also shows a repertoire of 1x1011 human antibody variable regions can generate large numbers of unique, biologically active scFvs against a variety of polypeptide targets (see e.g., at page 161-62 bridging paragraph and in Table 1, cited herewith).
Further, as another example in the art illustrating the potential scope of the genus of antibodies encompassed by the pending claim language, see also 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 (170OANPSEKNSP178); 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 $2A) 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 1683EPANPSEK175 sequence motif but the binding signal to the linear (Figure S$2B) 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 of Meyers bind within or nearby the rituximab 170ANPS173 epitope they do so with heavy and light chain CDRs non-homologous to those of rituximab.
The art establishes that even if multiple antibodies bind epitopes within the same small region of a given polypeptide, it is not uncommon for said antibodies to bind to different amino acid residues even within said small region and for said antibodies to have dissimilar CDRs.
The above cited evidence establishes the unpredictability in the art; one cannot readily visualize or recognize the identities of the members of the claimed genus that would be encompassed by the claim and possess both the required functional and structural characteristics claimed. Applicant was not in possession of all binders as claimed capable of the recited binding function. The characteristics defining the genus of binder are unknown as the recited language sets forth only what the binders do and now what they are. There is no disclosure of partial structure or other common structural feature, common to the members of the claimed genus encompassed by the claim, which are responsible for the recited/required function.
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 y. 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 be analogized as a search for a key on a ring with a million keys on it.
While it is within the skill level of the ordinary artisan to make and screen for antibodies having the claimed functional properties, one cannot envision their structure. Rather, the fact that screening would be necessary to determine which binders result in the desired functional ability (necessary in order to determine whether an antibody falls within the scope of the claim) is further evidence that the genus is not adequately described such to convey possession.
Screening amounts to only a plan for identifying the claimed antibodies, and is not a description of the antibodies themselves. Similarly, it was held in the University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004) that the disclosure of "assays for screening compounds, including peptides, polynucleotides, and small organic molecules to identify those that inhibit the expression or activity of the PGHS-2 gene product," did not satisfy the written description requirement for claims requiring administration of a "compound that selectively inhibits PGHS-2"). See also, Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company, 598 F.3d 1336, 1344 (Fed. Cir. 2010) (recognizing distinction between requirements for written description and enablement), and Centocor, 636 F.3d 1350 ("The fact that a fully-human antibody could be made does not suffice to show that the inventors ... possessed such an antibody.").
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.
For all of these reasons, the specification fails to convey evidence of possession of the entire genus of antibody that is limited to an antibody (as at claims 1 and 10).
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 1-2 and 7-10 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 1 provides for the use of an antibody that specifically binds to an amino acid set forth in SEQ ID NO: 1, but, since the claim does not set forth any steps involved in a method/process, it is unclear what method/process applicant is intending to encompass for measuring prohaptoglobin. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
Claim 1 is vague and indefinite because it is unclear how the prohaptoglobin amount provides determining that the subject has inflammatory bowel disease. Even though the claim recites “using the human prohaptoglobin amount as an indicator”, the claim fails to provide how the level provides the indication or provide steps to make a determination. For example, it is unclear if any amount or the mere presence indicates IBD, if the level is compared to something and an increase, decrease or equal amount indicates IBD or if the applicant intends something else. The claim fails to set forth any steps involved in the method/process, it is unclear what method/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
Claim 10 provides for the use of an antibody that specifically binds to an amino acid set forth in SEQ ID NO: 1, but, since the claim does not set forth any steps involved in a method/process, it is unclear what method/process applicant is intending to encompass for measuring prohaptoglobin. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claim 10 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
Claim Rejections - 35 USC § 103
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2 and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Fasano et al (US 2012/0107329) in view of Morishita et al (Analytical Biochemistry, 593, January 2020, pages 1-6) (submitted in the IDS filed 04/19/23) in light of Nishino et al (Oncotarget, Vol0., No. 16, January 29, 2018, pages 12732-12744) (submitted in the IDS filed 04/19/23).
Fasano et al discloses methods of diagnosing inflammatory diseases such as Crohn’s disease in a subject (e.g. abstract, para 0050). Fasano et al discloses the method comprises obtaining a biological sample from the subject and measuring an expression level of zonulin (prohaptoglobin) and comparing to that of a control wherein overexpression of the zonulin is indicative of the presence of the inflammatory disease (e.g. para’s 0042, 0050). Fasano et al discloses that the sample can be a serum sample (e.g. 0014, 0042).
Fasano et al differs from the instant invention in failing to teach subjecting the sample to a reduction treatment and the use of an antibody that specifically binds to an amino acid sequence of SEQ ID NO. 1.
Morishita et al teaches the same antibody as recited in claim 1, which specifically binds to an amino acid sequence of SEQ ID NO. 1 (QCKNYY), as recognizing prohaptoglobin. (e.g. page 2, col 1; pages 4-5). Morishita et al also teaches a reduction treatment is performed before the antibody binding step in detecting the prohaptoglobine (e.g. page 5, figure 3). As shown by Nishino et al page 12733 the western blot is performed under reducing conditions. Morishita et al teaches that this antibody recognizes structural change of glycoproteins dues to aberrant glycosylation and is specific for the epitope on the a chain of haptoglobin
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to incorporate an antibody such as taught by Morishita et al and a reduction treatment prior to the addition of the antibody because Morishita et al teaches that this antibody recognizes structural change of glycoproteins dues to aberrant glycosylation and is specific for the epitope on the a chain of haptoglobin. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating an antibody such as taught by Morishita et al and a reduction treatment for the detection of zonulin in the method of Fasano et al.
NOTE: It is noted that the Morishita et al publication and the current application have inventors in common. However, there is no evidence explaining the involvement of Yuta Maki, Shinji Takamatsu, Nami Ito, Sayaka Koda, Yoshihiro Kamada and Yasuhiro Kajihara and therefore the rejection has been made with the Morishita et al reference.
Claims 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Fasano et al and Morishita as applied to claims 1-2 and 9-10 above, and further in view of of Janeway et al. (Immunobiology: The Immune System in Health and Disease. 5th edition.New York: Garland Science; 2001, Appendix I, Immunologists Toolbox, 42 pages. )
See above for the teachings of Fasano et al and Morishita et al.
Fasano et al and Morishita et al differ from the instant invention
in that while they teach the use of antibodies specific for zonulin for diagnostic methods, they do not explicitly teach that such antibodies are joined to solid surfaces or are detectably labeled.
Janeway et al. teach that ELISAs are routine diagnostic assays in which antibodies are used to detect an antigen of interest, and that as part of such procedures antibodies can be attached to solid supports or be attached to detectable labels (see entire document, particularly sections A-6 and A-10 of pages 5-11).).
It would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to attach the antibodies in the modified method of Fasono et al. to solid supports and to detectable labels in order to practice the detection methods disclosed in the modified method of Fasano et al. as standard, routine laboratory assays make use of antibodies labeled in this manner as evidenced by Janeway et al. Thus, one of ordinary skill in the art would have a reasonable expectation of success to attach the antibodies in the modified method of Fasono et al. to solid supports and to detectable labels in order to practice the detection methods disclosed in the modified method of Fasano et al.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY W COUNTS whose telephone number is (571)272-0817. The examiner can normally be reached M-F 7:00-4:00.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678