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 .
Status of the claims
The amendment filed 10/07/26 is acknowledged and has been entered. Claims 1, 6-8, and 17-20 have been amended. Claims 9-10 and 15-16 have been canceled. Claims 2, 5, and 11-16 were previously canceled. Claims 17 and 20 remain withdrawn as being directed to non-elected inventions. Accordingly, claims 1, 3-4, 6-8 and 18-19 are under examination.
Withdrawn Rejections
Applicant’s arguments directed to the 102 and 103 rejections that the Examiner failed to correctly apply the level of the Pro-enkephalin or fragment thereof in the sample has been found persuasive. However, after review the references teach the levels and thus the following rejections have been made. Therefore, the office action has been made non-final because the Examiner failed to properly apply the levels in the rejection in the action mailed 07/07/25.
All remaining rejections not reiterated herein, have been withdrawn.
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, 3-4, 6-8 and 18-19 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 claim 1, the recited language limits the claims to 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 and forms a complex with Pro-Enkephalin or fragments thereof of at least 5 amino acids.
Regarding claim 1, the claims encompass a large genus of antibodies that may be characterized by substantial variability; put another way, the claimed genus encompasses many possible species of antibodies, polyclonal antibodies, antibody fragments, single chain 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 antibodies, every hybridoma created is going to produce a specific antibody, no two having the same sequence.
Even with specific binding agents such as 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 specific fragments as claimed (the binders are described only in terms of what they bind, i.e. the antigens to which they bind, rather than structure specific to the binders 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 binders 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 binder (e.g. 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 binders that are 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 binders encompassed by the recited language, from those excluded from the claim. As an example, consider binders that are antibodies: one cannot readily visualize what anti-enkephalin antibodies exhibit the desired binding functions, and bind one of the claimed fragments from those known anti-pro-enkephalin antibodies that do not bind these fragments. As presented (referring to claim 1), 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 pro-enkephalin. Having the sequences of the fragments as claimed (i.e., fragments to which the binder binds) fails to provide sufficient structure specific to the antibodies (binders) to allow one to distinguish what species achieve the desired binding functions from those that do not.
The originally filed specification fails to identify any particular species reading on the claimed genus.
“[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 binders such as antibodies, for example, that bind the very specific fragments identified by the claimed SEQ ID Nos.
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 antibodies 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 binders (e.g., just with respect to 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 antibodies as claimed capable of the recited binding function. The characteristics defining the genus of antibody 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.
Additionally, although the claims recite a process for obtaining the antibody, namely “wherein said at least one antibody is produced by a process comprising: injecting an animal with a Pro-Enkepahlin-peptide or a conjugate comprising a Pro- Enkepahlin-peptide, fusing activated B-cells from the animal after injection with a myeloma cell line and culturing the resulting cells, and selecting and culturing cells expressing the at least one antibody; or wherein said at least one antibody is a monoclonal antibody and is produced by a process of culturing cells expressing the monoclonal antibody, wherein said cells expressing the monoclonal antibody are generated by one of the following methods injecting an animal with a Pro-Enkephalin -peptide or a conjugate comprising a Pro- Enkephalin -peptide, fusing activated B-cells from the animal after injection with a myeloma cell line and culturing the resulting cells, and selecting said cells expressing the monoclonal antibody; or injecting an animal with a Pro-Enkephalin -peptide or a conjugate comprising a Pro- Enkephalin -peptide, fusing activated B-cells from the animal after injection with a hybridoma cell line to produce a trioma cell line and culturing the resulting cells, and selecting said cells expressing the monoclonal antibody; or injecting an animal with a Pro-Enkephalin -peptide or a conjugate comprising a Pro- Enkephalin -peptide, infecting activated B-cells from the animal after injection and culturing the resulting cells, and selecting the immortalized B-cells expressing the monoclonal antibody; or targeting a Pro-Enkephalin -peptide or a conjugate comprising a Pro-Enkephalin -peptide in a phage display; or selecting human monoclonal antibodies that bind to a target molecule using a human combinatorial monoclonal antibody library, wherein the target molecule is Pro-Enkephalin or a fragment thereof is selected from the group consisting of SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 5, SEQ ID No. 6, SEQ ID No. 8, SEQ ID No. 9, SEQ ID No. 10 and SEQ ID No. 11; wherein said Pro-Enkephalin or fragment thereof is selected from the group comprising SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 5, SEQ ID No. 6, SEQ ID No. 8, SEQ ID No. 9, SEQ ID No. 10 and SEQ ID No. 11, and wherein said level of Pro-Enkephalin or fragment thereof in the bodily fluid is above 150 pmol/L” (claim 1), such limitations are not sufficient to establish possession of the entire claimed genus, for example one cannot visualize the structure of every antibody encompassed, including those not yet produced/obtained.
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 (as at claim 1).
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.
Claim 8 is 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 8 is vague and indefinite in reciting “comprises two antibodies that bind to two different regions..” because it is unclear of one of the two antibodies is the labeled antibody recited in claim 7, if the two different antibodies are in addition to the labeled antibody or if the Applicant intends something else. Please clarify.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 3-4, 6, 18 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yokoyama et al (World Neurosurgery, 109, January 2018, pages E446-E459).
Yokoyama et al discloses a sample of serum from a subject such as a child <18 years of age (e.g. abstract, pgs E447-E448). Yokoyama et al discloses the sample is contacted with an antibody that is specific for proenkephalin and a complex is formed (e.g. E449-E450, E459). Yokoyama et al discloses the median age of the child is 7 (E448). Yokoyama et al discloses the subject has moyamoya disease) (is not diagnosed with kidney dysfunction) (e.g. E447, E450-E451). Yokoyama et al discloses the proenkephalin is sandwiched between two antibodies (e.g. 449, E459). Yokoyama et al discloses that the subject may have transient ischemic attack or cerebral infarction (life threatening condition = critically ill) (e.g. page E447). Yokoyama et al discloses that the assay uses anti-PENK 143-160 which bind within the region of current SEQ ID NO. 6 – 119-159). Yokoyama et al discloses that the level of the PENK in the serum sample can be above 150 pmol/L (e.g. figure 6, page E455). With respect to the recitation “wherein said antibody is produced by a process comprising: injecting an animal with a Pro-Enkepahlin-peptide or a conjugate comprising a Pro- Enkepahlin-peptide, fusing activated B-cells from the animal after injection with a myeloma cell line and culturing the resulting cells, and selecting and culturing cells expressing the at least one antibody; or wherein said at least one antibody is a monoclonal antibody and is produced by a process of culturing cells expressing the monoclonal antibody, wherein said cells expressing the monoclonal antibody are generated by one of the following methods injecting an animal with a Pro-Enkephalin -peptide or a conjugate comprising a Pro- Enkephalin -peptide, fusing activated B-cells from the animal after injection with a myeloma cell line and culturing the resulting cells, and selecting said cells expressing the monoclonal antibody; or injecting an animal with a Pro-Enkephalin -peptide or a conjugate comprising a Pro- Enkephalin -peptide, fusing activated B-cells from the animal after injection with a hybridoma cell line to produce a trioma cell line and culturing the resulting cells, and selecting said cells expressing the monoclonal antibody; or injecting an animal with a Pro-Enkephalin -peptide or a conjugate comprising a Pro- Enkephalin -peptide, infecting activated B-cells from the animal after injection and culturing the resulting cells, and selecting the immortalized B-cells expressing the monoclonal antibody; or targeting a Pro-Enkephalin -peptide or a conjugate comprising a Pro-Enkephalin -peptide in a phage display; or selecting human monoclonal antibodies that bind to a target molecule using a human combinatorial monoclonal antibody library, wherein the target molecule is Pro-Enkephalin or a fragment thereof is selected from the group consisting of SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 5, SEQ ID No. 6, SEQ ID No. 8, SEQ ID No. 9, SEQ ID No. 10 and SEQ ID No. 11; wherein said Pro-Enkephalin or fragment thereof is selected from the group comprising SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 5, SEQ ID No. 6, SEQ ID No. 8, SEQ ID No. 9, SEQ ID No. 10 and SEQ ID No. 11,”. These limitations are directed to a process of supplying or producing the antibody (product) for contacting with the body fluid. Thus the limitation reads as a product by process claim and determination of patentability is based on the product itself. The patentability of a product does not depend on the method of production and if the product in a product by process clam is the same or obvious from a product in the prior art then the claim is unpatentable. In the instant case, Yokoyama et al discloses an antibody consonant to the antibody as instantly recited and therefore the Yokoyama et al reads on the instantly recited claims.
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 7 is rejected under 35 U.S.C. 103 as being unpatentable over Yokoyama et al in view of Ernst et al (Peptides 27, 2006, pages 1835-1840) in light of Morgenthaler et al (Clin Chem, 2004; 50, pages 234-236).
Yokoyama et al differs from the instant invention in failing to teach the tracer antibody is labeled with chemiluminescent label.
Ernst et al teaches that it is known and conventional in the art to detect Proenkapalin with the use of a sandwich immunoassay wherein a chemiluminescent acridinium ester label is used (e.g. pgs 1836-1837). Ernset et al teaches that the assay components are prepared as described by Morgenthaler et al [23]. As shown by Morgenthaler et al (Clin Chem, 2004; 50, pages 234-236) the chemiluminescent label of Ernst et al is an acridinium ester (e.g. page 234). Ernest et al teaches that this provides for immunoreactivity detection in every serum and plasma sample (e.g. page 1838).
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 a chemiluminescent label such as taught by Ernest et al into the method of Yokoyama et al because Ernest et al shows that it is known and conventional in the art and also teaches that this provides for immunoreactivity detection in every serum and plasma sample. Thus, one of ordinary skill in the art would have a reasonable expectation of success incorporating a chemiluminescent label such as taught by Ernest et al into the method of Yokoyama et al.
Allowable Subject Matter
Claim 8 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(a), and 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action. The prior art of record does not teach nor fairly suggest two antibodies that bind to two different regions withing the region of Pro-Enkepalin that is SEQ ID NO: 13 and SEQ ID NO: 14 in a sample as currently recited.
Response to Arguments
Applicant's arguments filed 10/07/25 have been fully considered but they are not persuasive.
112(a) Written Description:
Applicant argues the “antibodies” recited in the claims of the current application is defined in the claims using a product-by-process limitation. Applicant later argues that the entire point of the existence of a product by process claim is to define a product by how it is made rather than its structure.
However, in response it is noted that the issue is not that the product (i.e., the antibodies) that is used in the claimed sample is recited in terms of product-by-process language, rather the issue is still that the product (antibodies) still is not sufficiently described in such a way that one having ordinary skill can readily visualize Applicant was in possession of the entire broad genus of antibodies including monoclonal, polyclonal, antibody fragments etc recited in the claim. Even when the labeling antibody is described by the how it is made (namely by the product-by-process limitations) and in terms of its function (i.e., its functional ability, namely it’s binding), without a known or disclosed correlation between that functional ability and the structure, there is insufficient description to support possession. In the present case, the product-by-process language describing the product, namely describing how the antibody is made, is merely providing the manner in which the antibodies may be discovered (an assay for screening to identify some antibody binders that fall within the scope). Such limitations do nothing to predict or suggest any particular structure specific to the antibody itself. One of skill in the art cannot simply use any commercially available antibody as the binder in the present claims, rather one must screen and locate those which fall within the scope of the claims. At best the product-by-process limitations merely predict function, which as discussed in the rejection, function alone is not sufficient written description.
Further, reciting the antibody using product-by-process language does not change the written description requirements for the claimed antibody. The antibody is an essential element required for performing the binding to the pro-Enkephalin in the sample.
Although the claims recite a process for obtaining the antibody, namely “wherein said at least one antibody is produced by a process” as instantly recited, such limitations are not sufficient to establish possession of the entire claimed genus, for example because one cannot visualize from the process of producing the product, any particular structure /structural element specific of every antibody/binder encompassed by the functional language used in the claim in order to sufficiently describe the antibody, for example, one cannot (from these claimed limitations) visualize those species which would include even those not yet produced.
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.").
Applicant argues that the fact that there is product-by-process written description methodology clearly explained in the MPEP (MPEP 2163) and caselaw it cites is rather strong evidence that such is a valid way of defining a claim element in lieu of defining the element by a generic structure. Appellant argues the entire purpose of product-by-process claiming since its inception was to allow a product to be claimed when the structure is not known.
This argument is not found persuasive, it is noted that MPEP 2113 states:
"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979)
In the present case, the recited process for obtaining the antibody does nothing to further elaborate on its structure in a way that would allow one to recognize a structure-function correlation. Put another way, the recited process for making the product does not apply any additional structure (does not provide additional structure/structural elements that can be attributed to the recited binding function that is also claimed, i.e., fails to further describe a structure-function relationship). The claims, at most, are describing the binder in terms of what/how it binds and how it’s made, and provide no structure specific to the binder/antibody itself.
Applicant further argues that MPEP 2163(II)(A)(3)(a)(i) discusses both product claims and product by process claims stating, “For example, disclosure of only a method of making the invention and the function may not be sufficient to support a product claim other than a product-by-process claim.” That is, this section of the MPEP is explaining that a product-by-process claim is different from a product claim on this issue, i.e., where a method of making the invention can support a claim. This section MPEP says no to product claims but yes to product-by-process claims. In the current application, the relevant portion of these claims, i.e., the labeling antibody, is defined by a product-by-process claim and the MPEP section above is clearly teaching that a method of making the invention can support such a claim.
This argument is not found persuasive because the section which Applicant cites is the section “i) For Each Claim Drawn to a Single Embodiment or Species:”. See also at this section:
Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the inventor was in possession of the claimed species is sufficient. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
The paragraph containing to the Applicant referenced citation states:
In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. For example, disclosure of only a method of making the invention and the function may not be sufficient to support a product claim other than a product-by-process claim. See, e.g., Fiers v. Revel, 984 F.2d at 1169, 25 USPQ2d at 1605; Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021. Where the process has actually been used to produce the product, the written description requirement for a product-by-process claim is clearly satisfied; however, the requirement may not be satisfied where it is not clear that the acts set forth in the specification can be performed, or that the product is produced by that process. Furthermore, disclosure of a partial structure without additional characterization of the product may not be sufficient to evidence possession of the claimed invention. See, e.g., Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021.
In referring to the particularly cited sentence Applicant references, namely “Where the process has actually been used to produce the product, the written description requirement for a product-by-process claim is clearly satisfied”, this is referring to the structure described by the product (see again, MPEP 2113, “The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims”). In the present case, the issue is that the structure implied by the process recited for producing the product, does not provide sufficient structure to meet the requirement for written description of the binder. The present claims are not limited to a particularly identified or claimed structure, so in the present case, the process is not used to produce a sufficiently described product. The binder is an essential element of the claim, and the fact is there is not sufficient description such that one can readily visualize the species encompassed by the present claims (one cannot readily visualize those species that meet the functional requirements, and bind as presently claimed). Knowing structure of the antigen to which the antibody binds, does nothing to provide structure specific to the binder itself.
The issue remains that although the product (labeling antibody) required of the claimed method for preparing a sample is described in terms of limitations which amount to a plan for screening for antibodies having the desired functional ability, the issue remains that both the process of producing the antibody and the functional language recited at best only describe a genus of antibody based on functional activity alone. While functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, that is not the case presently. Rather, in the present case, neither knowing the process by which the claimed binders are produced, nor knowing their desired binding activity, allows one to readily visualize a structure-function correlation. None the recited limitations, imply or suggest any particular structure responsible for the claimed functional (binding) activity. 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.
Applicants remaining arguments a moot in view of the new grounds of rejection.
Conclusion
No claims are allowed.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678
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