DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the claims
The amendment filed 09/22/25 is acknowledged and has been entered. Claims 1, 12 and 23 have been amended. New claims 24-37 have been added. Claims 4-6 and 15 have been canceled. Claims 2-3, 11, 14, 16 and 18-22 were previously canceled. Claim 17 remains withdrawn as being directed to a non-elected invention. Accordingly, claims 1, 7-10, 12-13 and 23-37 are under examination.
Withdrawn Rejections
All rejections of claims not reiterated herein, have been withdrawn.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, 7-10, 12-13 and 23-37 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, 24 and 31, the recited language limits the claims to a labeled 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-neurotensin 1-117 (SEQ ID NO: 5) or fragments thereof having at least 5 amino acids.
Regarding claims 1, 24 and 31, 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 such monoclonal antibodies, polyclonal antibodies and antibody fragments 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.
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 binders by what they do, and as a result places no limitations on the sequences/structure of the binders themselves (rather defines the binders only in terms of desired binding properties, thereby limiting the binders 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 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-neurotesin antibodies that do not bind these fragments. As presented (referring to claims 1, 24 and 31), 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 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 binders 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 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.
Additionally, although the claims recite a process for obtaining the binder, namely “wherein the binder is obtainable by a process comprising: fusing activated B-cells from a mammal previously immunized with a peptide that has a fragment of pro-neurotensin (SEQ ID NO. 5) with cells of a myeloma cell line, screening for cultures of said fused cells that comprises a pro-neurotensin (SEQ ID NO. 5) specific binder” (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/binder 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 antibodies (as at claims 1, 24 and 31).
Written Description
Claims 1, 7-10, 12 and 23-37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 7-10, 12 and 23-37 are directed to a methods of preparing a sample comprising pro-neurotensin 1-117 (SEQ ID NO:5) or peptide fragments of at least 5 amino acids bound to a labeling antibody
The claims as a whole therefore encompass a genus of pro-neurotensin 1-117 SEQ ID NO:5) or any fragments thereof which are defined by reference to a desired functional characteristic, namely the capacity to be bound by labeling antibody that binds to a part thereof.
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.
In this case, the genera encompassed by the claims are of large size and substantial variability. For example, the currently recited claims encompasses a part (fragments) of pro-neurotensin (SEQ ID NO: 5) of any length having 5 amino acids of the pro-neurotensin and any and all species of the pro-neurotensin including any protein having 5 of the amino acids of the recited pro-neurotensin. Any and all peptide fragments of an pro-neurotensin (SEQ ID NO: 5) would meet the structural requirements of the claim. Modifications, deletions, substitutions, additions, and insertions are also encompassed by the currently recited claims.
Thus, the claimed parts may involve any number of substitutions, deletions, and/or additions made relative to the pro-neurotensin (SEQ ID NO: 5) sequence, at any position within the proteins/ fragments. There is no defined epitope and the claim does not make clear if the 5 amino acids are contiguous, separated etc. The current claim even encompasses a protein which may have 5 amino acid of the pro-neurotensin (SEQ ID NO: 5) protein. As a result, the number of species meeting the structural requirements of the claim is exceedingly large and characterized by substantial variability. It is not apparent that the identities of all such species could be determined even with the aid of a computer.
However, only those sequences meeting the structural and functional requirements of the genus are encompassed by the claim. Therefore, the claims encompass all of the sequences meeting the structural requirements that are also able to be recognized by lubricin. In this case, however, it cannot be envisioned based on the specification what sequences would possess such binding properties. In particular, it cannot be envisioned based on the specification which part of SEQ ID NO: 5 would be capable of being recognized by the labeling antibody.
The specification on page 13 discloses an immunoassay for quantification of human pro-neurotensin (SEQ ID NO:5) wherein labeled antibody binds the pro-neurotesin. This is the only example in the specification providing binding of an antibody (which is unnamed or unidentified) as binding to the recited pro-neurotensin. The specification on pages 7-8 discloses 10 different fragments of pro-neurotensin wherein one of the fragments is disclosed as pro-neurotensin 1-117 (SEQ ID NO:5). There is not a single disclosure of a fragment of SEQ ID NO: 5 which possesses the unique capability of binding to the labeled antibody.
The specification does not disclose the detection and complexes of any and all possible pro-neurotensin (SEQ ID NO: 5) fragments or provide for labeling antibodies which binds to any and all possible pro-neurotensin (SEQ ID NO: 5) fragments
Comparing the claim scope with the scope of the description, it is noted that the specification as filed discloses only pro-neuroteins (SEQ ID NO: 5) complexed with labeling antibody. This disclosure of only the protein and fragments fails to convey evidence of possession of the entire genus. In particular, the specification fails to disclose a correlation between structure and function; the specification does not make clear which peptides or what 5 amino acids are in the genus and which are not because it does not set forth a physical basis for the claimed binding activity. As such, apart from pro-neurotensin (SEQ ID NO: 5), it is not known what pro-neurotensin parts (fragments) thereof would also bind to labeling antibodies which are specific to the pro-neurotensin (SEQ ID NO: 5) fragments. It is unknown what modifications would be permitted while retaining the ability to be recognized by capture proteins.
At the time of the invention, it was recognized that analysis of a given amino acid sequence only provides rough guides as to whether the sequence will bind to antibody. See Lesniewski et al. (U.S. 6,596,476 B1) at column 5, lines 40-47, who further teach that there is no invariably predictable way to ensure whether a sequence has immunological activity short of preparing the sequence and testing it in an assay. As such, it cannot be predicted what parts of pro-neurotensin (SEQ ID NO:5) would be recognized by an antibody in sample.
Furthermore, it was known in the prior art that small changes in antigen structure profoundly affect antibody-antigen interactions. Harlow & Lane (Harlow, E. and Lane, D., Antibodies: A Laboratory Manual (1988) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pages 23-26) discus how even small changes in antigen structure can profoundly affect the strength of an antibody-antigen interaction. See entire selection, in particular page 26, first full paragraph. In particular, the loss of a single hydrogen bond can reduce the strength of interaction by 1000-fold (ibid).
Many other researchers have reported similar findings to those of Harlow & Lane. For example, Lederman et al. ("A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4" Mol Immunol. 1991 Nov;28(11):1171-81) found that a single amino acid substitution on the antigen CD4 ablated binding of a monoclonal antibody (see title and abstract). Similarly, Colman et al. (Research in Immunology, 1994; 145(1): 33-36) teach that amino acid changes in an antigen can effectively abolish antibody antigen binding entirely (see entire document, particularly pages 33-34).
As noted above, the variability among the parts (fragments) encompassed by the claims is also enormous; and would encompass changes much more substantial than the loss of a single hydrogen bond or the mutation of a single amino acid; yet even such minor changes as these were known to dramatically affect function.
Given the unpredictability associated with making even minor changes to antigen structure while preserving function, with limited exception it is not possible to predict which, out of the enormous number of parts (fragments) encompassed by the claims, would be capable of being recognized by a binding agent (antibody).
For all of these reasons, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope 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 1, 7-10, 12-13 and 23-37 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 the recitation “or fragments thereof of at least 5 amino acids comprising peptides bound to the labeling antibody” is vague and indefinite because it is unclear if; the 5 amino acids are a part of the antibody fragment, a part of the pro-neurotensin 1-117 or if the Applicant intends something else. Also, it is unclear if the 5 amino acids comprising the peptides bound to the labeling antibody are referring to the pro-neurotensin peptides or if the applicant is referring to other peptides. Please clarify. See also deficiencies found in claims 24 and 31.
Response to Arguments
Applicant's arguments filed 09/22/25 have been fully considered but they are not persuasive.
112(a) Written Description:
Applicant argues the “labeling antibody” recited in the claims of the current application is defined in the claims using a product-by-process limitation. Applicant 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 labeling antibody) that is used in the claimed method (the method or preparing a sample) is recited in terms of product-by-process language, rather the issue is still that the product (labeling antibody) 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 method for preparing a sample as claimed (e.g. claims 1, 24 and 31).
Although the claims recite a process for obtaining the antibody, namely “wherein the 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 Appellant 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.
Allowable Subject Matter
Claims 1, 7-10, 12-13 and 23-37 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 a method as claimed wherein the level of the pro-neurotensin 1-117 (SEQ ID NO:5) bound to the labeling antibody in the bodily fluid sample is above 125 pmol/l.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/GARY COUNTS/ Primary Examiner, Art Unit 1678
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