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 .
Drawings
The drawings were received on 28 January 2025. These drawings are acceptable.
Claim Interpretation
Attention is directed to MPEP 904.01 [R-08.2012].
The breadth of the claims in the application should always be carefully noted; that is, the examiner should be fully aware of what the claims do not call for, as well as what they do require. During patent examination, the claims are given the broadest reasonable interpretation consistent with the specification. See In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is noted with particularity that narrowing limitations found in the specification cannot be inferred in the claims where the elements not set forth in the claims are linchpin of patentability. In re Philips Industries v. State Stove & Mfg. Co, Inc., 186 USPQ 458 (CA6 1975). While the claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims. On the contrary, claims must be interpreted as broadly as their terms reasonably allow. See Ex parte Oetiker, 23 USPQ2d 1641 (BPAI, 1992). In added support of this position, attention is directed to MPEP 2111 [R-11.2013], where, citing In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-51 (CCPA 1969), is stated:
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.
Additionally, attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Attention is also directed to MPEP 2111.02 II [R-07.2022]. As stated herein:
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
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The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")… (Emphasis added)
Attention is directed to MPEP 2111 [R-10.2019]. As stated therein:
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1). (Emphasis added).
Claim Rejections - 35 USC § 112, (b) / Second Paragraph
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.
Standard for Definiteness.
Attention is directed to MPEP 2171 [R-11.2013]:
Two separate requirements are set forth in 35 U.S.C. 112(b) and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the inventor or a joint inventor for a patent regards as his or her invention. Note that although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of the inventor or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
Attention is directed to MPEP 2173.02 I [R-07.2022]:
During prosecution, applicant has an opportunity and a duty to amend ambiguous claims to clearly and precisely define the metes and bounds of the claimed invention. The claim places the public on notice of the scope of the patentee’s right to exclude. See, e.g., Johnson & Johnston Assoc. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1052, 62 USPQ2d 1225, 1228 (Fed. Cir. 2002) (en banc). As the Federal Circuit stated in Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008):
“We note that the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiners demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation.”
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During examination, after applying the broadest reasonable interpretation to the claim, if the metes and bounds of the claimed invention are not clear, the claim is indefinite and should be rejected. Packard, 751 F.3d at 1310 (“[W]hen the USPTO has initially issued a well-grounded rejection that identifies ways in which language in a claim is ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention, and thereafter the applicant fails to provide a satisfactory response, the USPTO can properly reject the claim as failing to meet the statutory requirements of § 112(b).”); Zletz, 893 F.2d at 322, 13 USPQ2d at 1322.
Attention is also directed to MPEP 2173.02 III B, which states in part:
To comply with 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, applicants are required to make the terms that are used to define the invention clear and precise, so that the metes and bounds of the subject matter that will be protected by the patent grant can be ascertained. See MPEP § 2173.05(a), subsection I. It is important that a person of ordinary skill in the art be able to interpret the metes and bounds of the claims so as to understand how to avoid infringement of the patent that ultimately issues from the application being examined. See MPEP § 2173.02, subsection II (citing Morton Int ’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470 (Fed. Cir. 1993)); see also Halliburton Energy Servs., 514 F.3d at 1249, 85 USPQ2d at 1658 (“Otherwise, competitors cannot avoid infringement, defeating the public notice function of patent claims.”). Examiners should bear in mind that “[a]n essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.” Zletz, 893 F.2d at 322, 13 USPQ2d at 1322 [Fed. Cir. 1989]. (Emphasis added)
Attention is also directed to MPEP 2173.04 [R-10.2019], which states in part:
A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim). (Emphasis added)
Holding and Rationale
Claims 1, 5, 7, 9, 21, 24, 29, 34, 58, 116, and 220-227 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.
Claims 1 and 116, the only independent claims pending, are indefinite with respect to just which polypeptides are encompassed by the claimed methods. Said claims are also indefinite with respect to just which aspect(s) is/are subject to “analyzing”.
Claims 1 and 116 are indefinite with respect to what constitutes the metes and bounds of the “targeting moiety” of the “molecular probe”.
Claims 1 and 116 are indefinite with respect to just which property/properties of the “polypeptide” is the focus of “analyzing”. While claim 1, for example, concludes with one “obtain[ing] the location of the polypeptide in the sample”, it is unclear if this is the only aspect to be analyzed, or whether additional aspects can be the focus of analysis.
Claims 5, 7, 9, 21, 24, 29, 34, 58, 116, and 220-226, which depend from claim 1, and claim 227, which depends from claim 116, fail to overcome all identified aspects and are similarly rejected.
Response to traversal
Applicant’s representative, at pages 8-9 of the response of 03 November 2025, hereinafter the response, traverses the rejection of claims under 35 USC 112 (b). At page 9 of the response said representative asserts:
Specifically, "polypeptide" is expressly defined in paragraph [0032] of the application as "a molecule comprising a chain of two or more amino acids joined by peptide bonds." This definition along with the plain meaning of the term provide the necessary metes and bounds for the term and scope of the claim because it defines the molecule as being a chain of two or more amino acids joined by peptide bonds. The Office's concern as to the number of amino acids in the polypeptide chain is a question of breadth, which cannot be equated with indefiniteness as a matter of law. Therefore, all the claims are definite. (Emphasis added)
The above argument has been considered and has not been found persuasive to the withdrawal of the rejection. As an initial matter, it is unclear as to just which polypeptides are encompassed by the claimed method. While attention has been directed to the definition provided, it is noted with particularity that the definition does no resolve this issue as the term “more” is a relative term that renders the definition indefinite as it is less than clear as to just how many “more” amino acids can be present. Given such, the rejection is maintained.
Claim Rejections - 35 USC § 112, Written Description
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.
Standard for Written Description.
Attention is directed to MPEP 2163.02 Standard for Determining Compliance With the Written Description Requirement [R-07-2022]:
An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. (Emphasis added)
Attention is also set directed to MPEP 2161.01 I [R-07-2022], wherein is stated:
For instance, generic claim language in the original disclosure does not satisfy the written description requirement if it fails to support the scope of the genus claimed. Ariad, 598 F.3d at 1349-50, 94 USPQ2d at 1171 ("[A]n adequate written description of a claimed genus requires more than a generic statement of an invention’s boundaries.") (citing Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1405-06); Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002) (holding that generic claim language appearing in ipsis verbis in the original specification did not satisfy the written description requirement because it failed to support the scope of the genus claimed); Fiers v. Revel, 984 F.2d 1164, 1170, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (rejecting the argument that "only similar language in the specification or original claims is necessary to satisfy the written description requirement").
As set forth in Fiers v. Revel 25 USPQ2d 1601, 1604-5 (CAFC, January 1993):
We thus determined that, irrespective of the complexity or simplicity of the method of isolation employed, conception of a DNA, like conception of any chemical substance, requires a definition of that substance other than by its functional utility.
Fiers' attempt to distinguish Amgen therefore is incorrect. We also reject Fiers' argument that the existence of a workable method for preparing a DNA establishes conception of that material. (Emphasis added)
Conception of a substance claimed per se without reference to a process requires conception of its structure, name, formula, or definitive chemical or physical properties...
The difficulty that would arise if we were to hold that a conception occurs when one has only an idea of a compound, defining it by its hoped-for function, is that would-be inventors would file patent applications before they had made their inventions and before they could describe them. That is not consistent with the statute or the policy behind the statute, which is to promote disclosure of inventions.
As set forth in the en banc decision in Ariad Pharmaceuticals Inc. v. Eli Lilly and Company, 94 USPQ2d 1161 (Fed. Cir. 2010) at 1171:
We held that a sufficient description of a genus instead requires the disclosure of either 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. at 1568-69. We explained that an adequate written description requires 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. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 [25 USPQ2d 1601] (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001)). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
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In Fiers, we rejected the argument that “only similar language in the specification or original claim is necessary to satisfy the written description requirement.” 984 F.2d at 1170 (emphasis added). Rather, we held that original claim language to “a DNA coding for interferon activity” failed to provide an adequate written description as it amounted to no more than a “wish” or “plan” for obtaining the claimed DNA rather than a description of the DNA itself. Id. at 1170-71. That Fiers applied § 112, first paragraph, during an interference is irrelevant for, as we stated above, the statute contains no basis for ignoring the description requirement outside of this context. And again in Enzo we held that generic claim language appearing in ipsis verbis in the original specification does not satisfy the written description requirement if it fails to support the scope of the genus claimed. 323 F.3d at 968. We concluded that “[a] claim does not become more descriptive by its repetition, or its longevity.” Id. at 969.
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The written description requirement also ensures that when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function—a problem that is particularly acute in the biological arts.
Attention is also directed to MPEP 2163 Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, “Written Description” Requirement [R-01-2024], at part II ii):
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ( "[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[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.' (internal quotation marks omitted).") (Emphasis added)
Attention is also directed to the decision of University of California v. Eli Lilly and Co. (CA FC, July 1997) 43 USPQ2d 1398 wherein is stated:
In claims involving chemical materials, generic formulas usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate written description of the claimed genus. In claims to genetic material, however, a generic statement such as “vertebrate insulin cDNA” or “mammalian cDNA,” without more, is not an adequate written description of the genus because it does not distinguish the claimed genus from others, except by function. It does not specifically define any of the genes that fall within its definition. It does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus. A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what it achieves as a result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.
Thus, as we have previously held, a cDNA is not defined or described by the mere name cDNA,” even if accompanied by the name of the protein that it encodes, but requires a kind of specificity usually achieved by means of the recitation of the sequence of nucleotides that make up the cDNA. See Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606.
Holding and Rationale
Claims 1, 5, 7, 9, 21, 24, 29, 34, 58, 116, and 220-227 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.
Claims 1 and 58 are deemed to be representative and, for convenience, are reproduced below.
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As a result of amendment, claims no longer specify that the method of analyzing is directed to “macromolecule, the macromolecule comprising a polypeptide”. It is noted, however, that the polypeptide is not limited in terms of size, function, and origin and thusly, fairly encompasses polypeptides that are a macromolecule. In support of this interpretation attention is directed to paragraph [0085], where examples of a macromolecule are provided, and which explicitly includes “polypeptides”. In support of this interpretation attention is directed to the disclosure where, at page 33, paragraph [0085], bridging to page 36, paragraph [0090], applicant provides the following description of the polypeptide macromolecules and their virtually unlimited sources. As asserted to therein:
[0085] In some embodiments, the macromolecules (e.g., proteins, polypeptides, or
peptides) are obtained from a sample that is a biological sample. In some embodiments, the sample comprises but is not limited to, mammalian or human cells, yeast cells, and/or bacterial cells. In some embodiments, the sample contains cells that are from a sample obtained from a multicellular organism. For example, the sample may be isolated from an individual. In some embodiments, the sample may comprise a single cell type or multiple cell types. In some embodiments, the sample may be obtained from a mammalian organism or a human, for example by puncture, or other collecting or sampling procedures. In some embodiments, the sample comprises two or more cells. (Emphasis added)
[0086] The sample may be a spatial sample, from which information regarding the spatial arrangement and/or location of anatomical features, morphological features, cellular
features, and/or subcellular features may be desired. In some embodiments, the sample is further processed by methods known in the art. For example, a sample is processed to remove, clear, or isolate cellular material (e.g., by centrifugation, filtration, etc.). The spatial sample may refer to a biological sample arranged such that constituents, portions, or regions of the sample may be referenced spatially (e.g. arranged in a planar format such as a tissue section on a slide).
[0087] In some embodiments, the biological sample may contain whole cells and/or live cells and/or cell debris. In some examples, a suitable source or sample, may include but is not limited to: biological samples, such as biopsy samples, cell cultures, cells (both primary cells and cultured cell lines), sample comprising cell organelles or vesicles, tissues and tissue extracts; of virtually any organism. For example, a suitable source or sample, may include but is not limited to: biopsy; fecal matter; bodily fluids (such as blood, whole blood, serum, plasma, urine, lymph, bile, aqueous humor, breast milk, cerumen (earwax), chyle, chyme, endolymph, perilymph, exudates, cerebrospinal fluid, interstitial fluid, aqueous or vitreous humor, colostrum, sputum, amniotic fluid, saliva, anal and vaginal secretions, gastric acid, gastric juice, lymph, mucus (including nasal drainage and phlegm), pericardia! fluid, peritoneal fluid, pleural fluid, pus, rheum, saliva, sebum (skin oil), sputum, synovial fluid, perspiration and semen, a transudate, vomit and mixtures of one or more thereof, an exudate (e.g., fluid obtained from an abscess or any other site of infection or inflammation) or fluid obtained from a joint (normal joint or a joint affected by disease such as rheumatoid arthritis, osteoarthritis, gout or septic arthritis) of virtually any organism, with mammalian-derived samples, including microbiomecontaining samples, being preferred and human-derived samples, including microbiomecontaining samples, being particularly preferred; environmental samples (such as air, agricultural, water and soil samples); microbial samples including samples derived from microbial biofilms and/or communities, as well as microbial spores; tissue samples including tissue sections, research samples including extracellular fluids, extracellular supematants from cell cultures, inclusion bodies in bacteria, cellular components including mitochondria and cellular periplasm. In some embodiments, the biological sample comprises a body fluid or is derived from a body fluid, wherein the body fluid is obtained from a mammal or a human. In some embodiments, the sample includes bodily fluids, or cell cultures from bodily fluids. In some of any of the provided embodiments, a sample, such as a fluid sample, may be deposited on a surface. For example, a liquid sample may be processed to prepare a cell spread on a solid surface such as a slide. In some embodiments, a sample or a portion thereof (such as analytes or
cells obtained from the sample) may be deposited in a polymer resin. In some cases, the
polymer resin comprises a hydrogel-forming natural or synthetic polymer.
[0088] In some embodiments, the sample is a tissue sample. A tissue can be prepared in any convenient or desired way for its use in any of the methods described herein. Fresh, frozen, fixed or unfixed tissues can be used. A tissue can be prepared, fixed or embedded using methods described herein or known in the art (Fischer et al., CSH Protoc (2008) pdb prot4991; Fischer et al., CSH Protoc (2008) pdb top36; Fischer et al., CSH Protoc. (2008) pdb. prot4988). The tissue can be freshly excised from an organism or it may have been previously preserved for example by freezing, embedding in a material such as paraffin (e.g. formalin fixed paraffin embedded samples), formalin fixation, infiltration, dehydration or the like. In some examples, a matrix-forming material can be used to encapsulate a biological sample, such as a tissue sample. In some cases, the sample is embedded in a paraffin block. For example, the spatial sample may be a formalin- fixed, paraffin-embedded (FFPE) section. Optionally, a tissue section can be attached to a solid support, for example, using techniques and compositions exemplified herein with regard to attaching nucleic acids, cells, viruses, beads or the like to a solid support (RamosVera et al., J Vet Diagn Invest. (2008) 20(4):393-413). As a further option, a tissue can be permeabilized and the cells of the tissue lysed when the tissue is in contact with a solid support. Standard conditions and reagents may be used for tissue permeabilization including incubation with any suitable detergents, Triton X-100, ethoxylated nonylphenol (Tergitol-type NP-40), Tween 20, Saponin, Digitonin, or acetone (Fischer et al., CSH Protoc (2008) pdb top36). (Emphasis added)
[0089] In some embodiments, the sample is a "planar sample" that is substantially planar, i.e., two dimensional. In some embodiments, a sample is deposited in a substrate or deposited on a solid surface. In some embodiments, the sample is a three dimensional sample. In some examples, a material or substrate (e.g. glass, metal, ceramics, organic polymer surface or gel) may contain cells or any combination of biomolecules derived from cells, such as proteins, nucleic acids, lipids, oligo/polysaccharides, biomolecule complexes, cellular organelles, extracellular vesicles, cellular debris or excretions. In some embodiments, the planar cellular sample can be made by, e.g., depositing cells or portions thereof on a planar surface, e.g., by centrifugation, by cutting a three dimensional object that contains cells into sections and mounting the sections onto a planar surface, i.e., producing a tissue section. In some embodiments, the sample is a tissue section that refers to a piece of tissue that has been obtained from a subject, fixed, sectioned (e.g., cryosectioning), and mounted on a planar surface, e.g., a microscope slide.
[0090] In some embodiments, the spatial sample (e.g., specimen or tissue sample) is treated to expand the sample. In some aspects, the spatial sample is preserved and expanded isotropically using a chemical process. For example, a tissue sample may be treated to attach anchors to biomolecules in the spatial sample, perform in situ polymer synthesis, perform mechanical homogenization, and perform specimen expansion (See e.g., Zhao et al., Nature Biotechnology (2017) 35(8):757-764; Chang et al., Nature Methods (2017) 14:593-599; Chang et al., Nature Methods (2016) 13(8):679-84; Tillberg et al., Nature Biotechnology (2016) 34:987-992; Chen et al., Science (2015) 347(6221):543-548; Asano et al., Current Protocols in Cell Biology (2018) 80(1):e56; Wassie et al., Nature Methods (2018) 16(1):33-41; Boyden et al., Mater. Horiz., (2019) 6, 11-13; Alon et al., FEBS J. 2019 Apr;286(8):1482-1494. Karagiannis et al., Current Opinion in Neurobiology (2018) 50:56-63; Gao et al., BMC Biology (2017) 15(1):50).
Applicant, at page 43, paragraph [0115], of the disclosure provides the following definition for molecular probes. As asserted to therein:
[0115] In some examples, the molecular probe comprises an antibody, an antigen-binding antibody fragment, a single-domain antibody (sdAb), a recombinant heavy-chain-only antibody (VHH), a single-chain antibody (scFv), a shark-derived variable domain (vNARs), a Fv, a Fab, a Fab', a F(ab')2, a linear antibody, a diabody, an aptamer, a peptide mimetic molecule, a fusion protein, a reactive or non-reactive small molecule, or a synthetic molecule. (Emphasis added)
[0116] In some embodiments, the molecular probe comprises a microprotein (cysteine
knot protein, knottin), a DARPin; a Tetranectin; an Affibody; an Affimer, a Transbody; an Anticalin; an AdNectin; an Affilin; a Microbody; a peptide aptamer; an alterase; a plastic antibody; a phylomer; a stradobody; a maxibody; an evibody; a fynomer, an armadillo repeat protein, a Kunitz domain, an avimer, an atrimer, a probody, an immunobody, a triomab, a troybody; a pepbody; a vaccibody, a UniBody; a DuoBody, a Fv, a Fab, a Fab', a F(ab')2, a peptide mimetic molecule, or a synthetic molecule (See e.g., Nelson, MAbs (2010) 2(1): 77-78, Goltsev et al., Cell. 2018 Aug 9;174(4):968-981, or as described in US Patent Nos. or Patent Publication Nos. US 5,475,096, US 5,831,012, US 6,818,418, US 7,166,697, US 7,250,297, US 7,417,130, US 7,838,629, US 2004/0209243, and/or US 2010/0239633).
[0117] In some embodiments, the molecular probe is capable of chemically binding, covalently binding, and/or reversible binding to the spatial sample. In some embodiments, the molecular probe binds to a moiety that is bound to, associated with or complexed with the macromolecule in the spatial sample. In some examples, the molecular probe binds to a macromolecule (e.g., target macromolecule), a moiety in proximity to the macromolecule, or a moiety associated or bound to the macromolecule in the spatial sample. In some embodiments, the molecular probe binds a moiety in proximity to the macromolecule such that transfer of information from a probe tag can be transferred to a recording tag allow association with the molecular probe. For example, the distance between the macromolecule and the moiety in proximity to the macromolecule is about 10 nm to 100 nm; about 10 nm to 500 nm, about 10 nm to 1,000 nm, about 10 nm to 5,000 nm, about 100 nm to 300 nm; about 100 nm to 600 nm; about 100 nm to 1,000 nm; about 100 nm to 5,000 nm; about 300 nm to 600 nm, about 300 nm to 1,000 nm; or 300 nm to 5,000 nm. In some cases, transfer of infom1ation from the probe tag to the recording tag can occur if the recording tag is in proximity to the probe tag, regardless where the molecular probe is bound to the macromolecule. In some embodiments, the molecular probe is attached to the probe tag via a linker which may be of various lengths. In some cases, the length of the linker between the molecular probe and the probe tag may increase the distance between a moiety in proximity to the molecular probe and the molecular probe which allows association to the molecular probe. In some embodiments, the proximity of the moiety to the macromolecule may depend on the length of any linkers used in the molecular probe to attach the probe tag.
As evidenced above, the polypeptide macromolecule can be from virtually any biological source.
Attention is directed to the following publications which teach of the enormity of the genera of virus, plants, insects, bacteria, mammals, and species encompassed by the subfamily Murinae as the detection of any and all genes from all members of the various genera are encompassed by the instant claims.
“Viruses” (Wikipedia.com, accessed 08 September 2023), teaches:
An enormous variety of genomic structures can be seen among viral species; as a group, they contain more structural genomic diversity than plants, animals, archaea, or bacteria. There are millions of different types of viruses, although fewer than 7,000 types have been described in detail. (Emphasis added)
“How many species of bacteria are there” (wisegeek.com; accessed 21 January 2014) teaches:
Currently, estimates of the total number of species of bacteria range from about 10 million to a billion, but these estimates are tentative, and may be off by many orders of magnitude. By comparison, there are probably between 10 and 30 million species of animals, the vast majority of them insects. The number of scientifically recognized species of animals is about 1,250,000. There are almost 300,000 recognized species of plants.
“Fungi,” (Wikipedia.com; accessed 08 September 2023), teaches:
As of 2020, around 148,000 species of fungi have been described by taxonomists,[6] but the global biodiversity of the fungus kingdom is not fully understood.[48] A 2017 estimate suggests there may be between 2.2 and 3.8 million species.[5]
“Insect”, (Wikipedia.com; accessed 09/10/2020) teaches:
Insects are the most diverse group of animals; they include more than a million described species and represent more than half of all known living organisms. The total number of extant species is estimated at between six and ten million; potentially over 90% of the animal life forms on Earth are insects.
“Plant,” (Wikipedia.com; accessed 08 September 2023) teaches:
There are about 380,000 known species of plants, of which the majority, some 260,000, produce seeds.
“Mammal,” (Wikipedia.com; accessed 08 September 2023) teaches:
According to Mammal Species of the World, which is updated through periodic editions, 5,416 species were identified in 2006. These were grouped into 1,229 genera, 153 families and 29 orders.[5]
“Murinae,” (Wikipedia.com, accessed 10 June 2024) teaches:
The Old World rats and mice, part of the subfamily Murinae in the family Muridae, comprise at least 519 species. Members of this subfamily are called murines. In terms of species richness, this subfamily is larger than all mammal families except the Cricetidae and Muridae, and is larger than all mammal orders except the bats and the remainder of the rodents.
“Fish,” (Wikipedia.com, accessed 08 September 2023) teaches:
Fish are abundant in most bodies of water. They can be found in nearly all aquatic environments, from high mountain streams (e.g., char and gudgeon) to the abyssal and even hadal depths of the deepest oceans (e.g., cush-eels and snailfish), although no species has yet been documented in the deepest 25% of the ocean.[4] At 34,300 described species, fish exhibit greater species diversity than any other group of vertebrates.[5]
“Archaea,” Wikipedia.com (accessed 08 September 2023), teaches:
The classification of archaea into species is also controversial. Ernst Mayr defined a species as a group of interbreeding organisms which are reproductively isolated, but this is of no help since archaea only reproduce asexually.[37]
Archaea show high levels of horizontal gene transfer between lineages. Some researchers suggest that individuals can be grouped into species-like populations given highly similar genomes and infrequent gene transfer to/from cells with less-related genomes, as in the genus Ferroplasma.[38] On the other hand, studies in Halorubrum found significant genetic transfer to/from less-related populations, limiting the criterion's applicability. Some researchers question whether such species designations have practical meaning.[40]
Current knowledge on genetic diversity is fragmentary, so the total number of species cannot be estimated with any accuracy.[22] (Emphasis added)
“Algae,” Wikipedia.com (accessed 03-04-2016) teaches:
The most recent estimate suggests 72,500 algal species worldwide.
“Protozoa,” Wikipedia.com (accessed 05-11-2016), teaches:
The classification of protozoa has been and remains a problematic area of taxonomy. Where they are available, DNA sequences are used as the basis for classification; however, for the majority of described protozoa, such material is not available. (Emphasis added)
A review of the disclosure does identify a Sequence Listing. The Sequence Listing, however, comprises but two DNA sequences of 20 and 24 nucleotides in length. Said sequences are also identified as being an “Artificial Sequence”, with their being further characterized as being a “P5 primer” and a “P7 primer”.
The disclosure has not been found to provide the amino acid sequence for any polypeptide, found in any organism, much less identify epitopes of same, and lesser still identify those molecular probes that will bind to each epitope on the genus of macromolecular polypeptides.
The disclosure has been found to comprise but a single example- “ Example 1 - Exemplary Assessment of Proteins in a Spatial Sample” (page 153).
As noted above in paragraph 39, applicant, at page 43, paragraph [0115], of the disclosure provides the following definition for molecular probes. As asserted to therein:
[0115] In some examples, the molecular probe comprises an antibody, an antigen-binding antibody fragment, a single-domain antibody (sdAb), a recombinant heavy-chain-only antibody (VHH), a single-chain antibody (scFv), a shark-derived variable domain (vNARs), a Fv, a Fab, a Fab', a F(ab')2, a linear antibody, a diabody, an aptamer, a peptide mimetic molecule, a fusion protein, a reactive or non-reactive small molecule, or a synthetic molecule. (Emphasis added)
A review of the disclosure fails to find where applicant has provided a representative number of each of the members of the genus of molecular probes for each member of the genus of macromolecules encompassed by the claims. Such non-disclosure of such essential materials of the claimed method has not been found to reasonably suggest that applicant, as of the effective priority date (May 20, 2019) was in possession of the genus of macromolecular polypeptides and the corresponding genus of molecular probes.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1, 5,7, 9, 21, 24, 29, 34, 58, 116, and 220-225 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.
Response to traversal
Applicant’s representative, at pages 9-16 of the response traverses the rejection of claims under 35 USC 112(a) for not satisfying the written description requirement.
At page 12 of the response said representative asserts:
Likewise, the specification discloses that a molecular probe binds to a macromolecule which includes a polypeptide, and this property (binding to a polypeptide) shared by the members of the genus is by itself sufficient to permit one skilled in the art to recognize members of the genus of molecular probes that are suitable for practicing the invention, because this property is well-known and defined in the art. (Emphasis added)
The above argument has been considered and has not been found persuasive towards the withdrawal of the rejection. While one may be able to recognize a “molecular probe” by nature of its binding, such does not demonstrate that applicant had possession of such probes at the time of filing. As noted above, Attention is also directed to MPEP 2163 Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, “Written Description” Requirement [R-01-2024], at part II ii):
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ( "[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[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.' (internal quotation marks omitted).") (Emphasis added)
The aspect of a “molecular probe” being capable of binding to a polypeptide found in any organism speaks to its function; however, such does not provide the physical characteristics of either the polypeptide or of the molecular probe, e.g., the nucleotide sequence of aptamers and/or the amino acid sequence of the antibodies. Such nondisclosure of such essential properties has not been found to reasonably suggest that applicant was in possession of the entire scope of the claimed invention.
Attention to US 6,300,093 B1 (Kindsvogel et al.), which teaches at column 22, last paragraph:
Antibodies of the present invention may be produced by immunizing an animal, a wide variety of warm-blooded animals such as horses, cows, goats, sheep, dogs, chickens, rabbits, mice, and rats can be used, with a recombinant or synthetic islet cell antigen polypeptide or a selected portion thereof (e.g., a peptide).
Attention is also directed to US 2003/0092624 A1 (Wang et al.). As disclosed at paragraph [0194]:
[0194] According to yet an additional aspect of the present invention there is provided an antibody, either polyclonal or monoclonal antibody, recognizing at least one epitope of the polypeptide described herein. The present invention can utilize serum immunoglobulins, polyclonal antibodies or fragments thereof, (i.e., immunoreactive derivative of an antibody), or monoclonal antibodies or fragments thereof. Monoclonal antibodies or purified fragments of the monoclonal antibodies having at least a portion of an antigen binding region, including, such as, Fv, F(ab1)2, Fab fragments (Harlow and Lane, 1988 Antibody, Cold Spring Harbor), single chain antibodies (U.S. Pat. No. 4,946,778), chimeric or humanized antibodies and complementarily determining regions (CDR)… Antibodies of the IgG class are made up of four polypeptide chains linked together by disulfide bonds. The four chains of intact IgG molecules are two identical heavy chains referred to as H-chains and two identical light chains referred to as L-chains. Additional classes includes IgD, IgE, IgA, IgM and related proteins. (Emphasis added)
Attention is also directed to US 2013/0338038 A1 (DuBridge et al.), which teaches the following at paragraph [0061]:
[0061] Examples of suitable sources for immunoglobulin genes include, but are not limited to, humans, primates, rodents (e.g., rat, mouse, hamster, guinea pig, etc.), non-rodents such as sheep, donkey, goat, horse, cow, pig, chicken, llama, camel, dog, cat, rabbit, fish, and birds. In addition to immunoglobulins obtained from various organisms, variant forms of known antibodies can be used, including humanized, chimeric, and monoclonal antibodies. Further, the immunoglobulin molecules or antibodies of the invention can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or subclass of immunoglobulin molecule. (Emphasis added)
As noted above, a review of the disclosure does identify a Sequence Listing. Said Sequence Listing comprises but 2 DNA sequences, both of which are identified as being an “Artificial Sequence”. The disclosure has not been found to provide the amino acid sequence for any protein, much less any “polypeptide” and lesser still the amino acid sequence for any antibody or antibody fragment that is produced by any organism. A review of the disclosure and of the response fails to identify where applicant has presented evidence supporting the position that they have possession of the broad genus of antibodies and antibody fragments where the antibodies have been produced by the broad genus of organisms recognized as being capable of producing antibodies. Such non-disclosure by applicant has not been found to satisfy the written description requirement.
At page 15 of the response said representative asserts:
In contrast, the methods of the present claims do not rely on the function or structure of a polypeptide since it can be practiced using any polypeptide because there are no specific structural or functional properties the polypeptide is required to have. Accordingly, the specification and claims recite a generic “polypeptide.” In fact, one of the advantages of the claimed method is that the identity of the polypeptide may be unknown before practicing the methods. When that is the case, the identity of the polypeptide may be inferred by comparing the sequence of the nucleic acid probe tag determined in step (d) to a sequence of the probe tag of the molecular probe, see, e.g., paragraphs [0372]-[0373] of the application as published. In other embodiments, the identity of the polypeptide may be determined by performing additional binding steps, as described in the present claim 58.
The above cited argument has been considered and has not been found persuasive. The aspect that the claimed method fairly encompasses the analysis of “any polypeptide” is deemed to encompass the analysis of each and every possible medically-significant polypeptide known at the time of filing the instant application as well as that which has become known and that which, at some point in the future will become known. Applicant’s non-disclosure of the amino acid sequence for any polypeptide has not been found to support the position that applicant had possession of each and every polynucleotide at the time of filing. Likewise, applicant’s nondisclosure of the antibodies produced by any organism, and which binds to each of the genus of polypeptides, has not been found to support the position that applicant, as of the effective filing date (20 May 2019), was in possession of the genus of “probes”.
In view of the above analysis and in the absence of convincing evidence to the contrary, the rejection is maintained.
Claim Rejections - 35 USC § 101 & 112
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.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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, 5, 7, 9, 21, 24, 29, 34, 58, 116, and 220-227 are rejected under 35 U.S.C. 101 because the claimed invention is not supported by either a specific, substantial, and credible asserted utility or a well-established utility.
Attention is also directed to MPEP 2107.02 I [R-07.2022], which states in part:
The claimed invention is the focus of the assessment of whether an applicant has satisfied the utility requirement. Each claim (i.e., each “invention”), therefore, must be evaluated on its own merits for compliance with all statutory requirements… Only where it can be established that other species clearly encompassed by the claim do not have utility should a rejection be imposed on the generic claim. In such cases, the applicant should be encouraged to amend the generic claim so as to exclude the species that lack utility. (Emphasis added)
Attention is also directed to MPEP 2106.03 II [R-07.2022]:
A claim whose BRI covers both statutory and non-statutory embodiments embraces subject matter that is not eligible for patent protection and therefore is directed to non-statutory subject matter. Such claims fail the first step (Step 1: NO) and should be rejected under 35 U.S.C. 101, for at least this reason. In such a case, it is a best practice for the examiner to point out the BRI and recommend an amendment, if possible, that would narrow the claim to those embodiments that fall within a statutory category.
Attention is also directed to MPEP 2107.01 I [R-07.2022], which states in part:
A. Specific Utility
A "specific utility" is specific to the subject matter claimed and can "provide a well-defined and particular benefit to the public." In re Fisher, 421 F.3d 1365, 1371, 76 USPQ2d 1225, 1230 (Fed. Cir. 2005). This contrasts with a general utility that would be applicable to the broad class of the invention. Office personnel should distinguish between situations where an applicant has disclosed a specific use for or application of the invention and situations where the applicant merely indicates that the invention may prove useful without identifying with specificity why it is considered useful. For example, indicating that a compound may be useful in treating unspecified disorders, or that the compound has "useful biological" properties, would not be sufficient to define a specific utility for the compound. See, e.g., In re Kirk, 376 F.2d 936, 153 USPQ 48 (CCPA 1967); In re Joly, 376 F.2d 906, 153 USPQ 45 (CCPA 1967). Similarly, a claim to a polynucleotide whose use is disclosed simply as a "gene probe" or "chromosome marker" would not be considered to be specific in the absence of a disclosure of a specific DNA target. See In re Fisher, 421 F.3d at 1374, 76 USPQ2d at 1232 ("Any EST [expressed sequence tag] transcribed from any gene in the maize genome has the potential to perform any one of the alleged uses…. Nothing about [applicant’s] seven alleged uses set the five claimed ESTs apart from the more than 32,000 ESTs disclosed in the [ ] application or indeed from any EST derived from any organism. Accordingly, we conclude that [applicant] has only disclosed general uses for its claimed ESTs, not specific ones that satisfy § 101."). A general statement of diagnostic utility, such as diagnosing an unspecified disease, would ordinarily be insufficient absent a disclosure of what condition can be diagnosed. Contrast the situation where an applicant discloses a specific biological activity and reasonably correlates that activity to a disease condition. Assertions falling within the latter category are sufficient to identify a specific utility for the invention. Assertions that fall in the former category are insufficient to define a specific utility for the invention, especially if the assertion takes the form of a general statement that makes it clear that a "useful" invention may arise from what has been disclosed by the applicant. Knapp v. Anderson, 477 F.2d 588, 177 USPQ 688 (CCPA 1973).
B. Substantial Utility
"[A]n application must show that an invention is useful to the public as disclosed in its current form, not that it may prove useful at some future date after further research. Simply put, to satisfy the ‘substantial’ utility requirement, an asserted use must show that the claimed invention has a significant and presently available benefit to the public." Fisher, 421 F.3d at 1371, 76 USPQ2d at 1230. The claims at issue in Fisher were directed to expressed sequence tags (ESTs), which are short nucleotide sequences that can be used to discover what genes and downstream proteins are expressed in a cell. The court held that "the claimed ESTs can be used only to gain further information about the underlying genes and the proteins encoded for by those genes. The claimed ESTs themselves are not an end of [the inventor’s] research effort, but only tools to be used along the way in the search for a practical utility…. [Applicant] does not identify the function for the underlying protein-encoding genes. Absent such identification, we hold that the claimed ESTs have not been researched and understood to the point of providing an immediate, well-defined, real world benefit to the public meriting the grant of a patent." Id. at 1376, 76 USPQ2d at 1233-34). Thus a "substantial utility" defines a "real world" use. Utilities that require or constitute carrying out further research to identify or reasonably confirm a "real world" context of use are not substantial utilities. For example, both a therapeutic method of treating a known or newly discovered disease and an assay method for identifying compounds that themselves have a "substantial utility" define a "real world" context of use. An assay that measures the presence of a material which has a stated correlation to a predisposition to the onset of a particular disease condition would also define a "real world" context of use in identifying potential candidates for preventive measures or further monitoring. On the other hand, the following are examples of situations that require or constitute carrying out further research to identify or reasonably confirm a "real world" context of use and, therefore, do not define "substantial utilities":
(A) Basic research such as studying the properties of the claimed product itself or the mechanisms in which the material is involved;
(B) A method of treating an unspecified disease or condition;
(C) A method of assaying for or identifying a material that itself has no specific and/or substantial utility;
(D) A method of making a material that itself has no specific, substantial, and credible utility; and
(E) A claim to an intermediate product for use in making a final product that has no specific, substantial and credible utility.
Office personnel must be careful not to interpret the phrase "immediate benefit to the public" or similar formulations in other cases to mean that products or services based on the claimed invention must be "currently available" to the public in order to satisfy the utility requirement. See, e.g., Brenner v. Manson, 383 U.S. 519, 534-35, 148 USPQ 689, 695 (1966). Rather, any reasonable use that an applicant has identified for the invention that can be viewed as providing a public benefit should be accepted as sufficient, at least with regard to defining a "substantial" utility.
C. Research Tools
Some confusion can result when one attempts to label certain types of inventions as not being capable of having a specific and substantial utility based on the setting in which the invention is to be used. One example is inventions to be used in a research or laboratory setting. Many research tools such as gas chromatographs, screening assays, and nucleotide sequencing techniques have a clear, specific and unquestionable utility (e.g., they are useful in analyzing compounds). An assessment that focuses on whether an invention is useful only in a research setting thus does not address whether the invention is in fact “useful” in a patent sense. Instead, Office personnel must distinguish between inventions that have a specifically identified substantial utility and inventions whose asserted utility requires further research to identify or reasonably confirm. Labels such as “research tool,” “intermediate” or “for research purposes” are not helpful in determining if an applicant has identified a specific and substantial utility for the invention.
IV. RELATIONSHIP BETWEEN 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, FIRST PARAGRAPH, AND 35 U.S.C. 101
A deficiency under the utility prong of35 U.S.C. 101 also creates a deficiency under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. See In re Brana, 51 F.3d 1560, 34 USPQ2d 1436 (Fed. Cir. 1995); In re Jolles, 628 F.2d 1322, 1326 n.10, 206 USPQ 885, 889 n.11 (CCPA 1980); In re Fouche, 439 F.2d 1237, 1243, 169 USPQ 429, 434 (CCPA 1971) (“If such compositions are in fact useless, appellant’s specification cannot have taught how to use them.”). Courts have also cast the 35 U.S.C. 101/35 U.S.C. 112 relationship such that 35 U.S.C. 112 presupposes compliance with 35 U.S.C. 101. See In re Ziegler, 992 F.2d 1197, 1200-1201, 26 USPQ2d 1600, 1603 (Fed. Cir. 1993) (“The how to use prong of section 112 incorporates as a matter of law the requirement of 35 U.S.C. 101 that the specification disclose as a matter of fact a practical utility for the invention. ... If the application fails as a matter of fact to satisfy 35 U.S.C. § 101, then the application also fails as a matter of law to enable one of ordinary skill in the art to use the invention under 35 U.S.C. § 112.”); In re Kirk, 376 F.2d 936, 942, 153 USPQ 48, 53 (CCPA 1967) (“Necessarily, compliance with § 112 requires a description of how to use presently useful inventions, otherwise an applicant would anomalously be required to teach how to use a useless invention.”). For example, the Federal Circuit noted, “[o]bviously, if a claimed invention does not have utility, the specification cannot enable one to use it.” In re Brana, 51 F.3d 1560, 34 USPQ2d 1436 (Fed. Cir. 1995). As such, a rejection properly imposed under 35 U.S.C. 101 for lack of utility should be accompanied with a rejection under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph. It is equally clear that a rejection based on “lack of utility,” whether grounded upon 35 U.S.C. 101 or 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, rests on the same basis (i.e., the asserted utility is not credible).
As presently worded, claims 1, 5, 7, 9, 21, 24, 29, 34, 58, 116, and 220-227 are drawn to “a method of analyzing a polypeptide”.
The claims do not distinguish between those polypeptides that do and do not have utility under 35 USC 101 but rather, encompasses any and all manner of polypeptides. In support of this interpretation attention is directed to page 15 of the response of 03 November 2025 where applicant asserts:
[T]the methods of the present claims do not rely on the function or structure of a polypeptide since it can be practiced using any polypeptide because there are no specific structural or functional properties the polypeptide is required to have. Accordingly, the specification and claims recite a generic “polypeptide.” In fact, one of the advantages of the claimed method is that the identity of the polypeptide may be unknown before practicing the methods. (Emphasis in original)
While the claims currently before the Office are all drawn to a method and not to a product, such does not alter the requirements of satisfying the utility requirements of 35 USC 101. In support of this position, attention is directed to Brenner, Comr. Pats. v. Manson, 148 USPQ 689 (US 1966):
Until the process claim has been reduced to production of a product shown to be useful, the metes and bounds of that monopoly are not capable of precise delineation. It may engross a vast, unknown, and perhaps unknowable area. Such a patent may confer power to block off whole areas of scientific development, 22 without compensating benefit to the public. The basic quid pro quo contemplated by the Constitution and the Congress for granting a patent monopoly is the benefit derived by the public from an invention with substantial utility. Unless and until a process is refined and developed to this point-where specific benefit exists in currently available form-there is insufficient justification for permitting an applicant to engross what may prove to be a broad field. (Emphasis added)
* * *
We find absolutely no warrant for the proposition that although Congress intended that no patent be granted on a chemical compound whose sole "utility" consists of its potential role as an object of use-testing, a different set of rules was meant to apply to the process which yielded the unpatentable product. 24 That proposition seems to us little more than an attempt to evade the impact of the rules which concededly govern patentability of the product itself.
This is not to say that we mean to disparage the importance of contributions to the fund of scientific information short of the invention of something "useful," or that we are blind to the prospect that what now seems without "use" may tomorrow command the grateful attention of the public. But a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.
For "specific utility", the invention must have a utility specific to the subject matter claimed in contrast with a general utility that would be applicable to the broad class of the invention. According to 35 U.S.C. 101, a specific utility is not a list of potential applications for which the broad class of the invention would also have utility.
Applicants' disclosure is directed to chromosomal or genetic loci’s alternations that are generic to essentially any nucleic acid allele, allelic variants, or combination(s) thereof. The claimed determination of the broad range of the number of copies of two or more genomic loci in a broad class of genomic DNA sample amounts to a general utility of a broad class of diagnosis or modulation of a variety of genetic loci and for detection of related nucleic acids.
To be specific, the application must teach the skilled artisan in specific terms specific biological activities of a diagnosis utility, and reasonably correlate a genomic alteration of a genomic loci to a disease condition.
The claims fairly encompass the sequencing of the expressed sequence tags (ESTs; cDNA) at issue in Fisher. Indeed, as seen at 1227, one of the seven specified utilities was “identifying the presence or absence of a polymorphism” which is recognized as a form of sequencing. As in Fisher, the disclosure does not teach what one is to do with the resulting sequence information.
Fisher, at 1230, teaches:
Further, the Utility Guidelines discuss “research tools,” a term often given to inventions used to conduct research. The PTO particularly cautions that
[a]n assessment that focuses on whether an invention is useful only in a research setting thus does not address whether the invention is in fact “useful” in a patent sense. [The PTO] must distinguish between inventions that have a specifically identified substantial utility and inventions whose asserted utility requires further research to identify or reasonably confirm.
Id. The PTO's standards for assessing whether a claimed invention has a specific and substantial utility comport with this court's interpretation of the utility requirement of §101.
Fisher, at 1231:
Regarding the seven uses asserted by Fisher, we observe that each claimed EST uniquely corresponds to the single gene from which it was transcribed (“underlying gene”). As of the filing date of the ′643 application, Fisher admits that the underlying genes have no known functions. Fisher, nevertheless, claims that this fact is irrelevant because the seven asserted uses are not related to the functions of the underlying genes. We are not convinced by this contention. Essentially, the claimed ESTs act as no more than research intermediates that may help scientists to isolate the particular underlying protein-encoding genes and conduct further experimentation on those genes.
***
Fisher compares the claimed ESTs to certain other patentable research tools, such as a microscope. Although this comparison may, on first blush, be appealing in that both a microscope and one of the claimed ESTs can be used to generate scientific data about a sample having unknown properties, Fisher's analogy is flawed. As the government points out, a microscope has the specific benefit of optically magnifying an object to immediately reveal its structure. One of the claimed ESTs, by contrast, can only be used to detect the presence of genetic material having the same structure as the EST itself. It is unable to provide any information about the overall structure let alone the function of the underlying gene. Accordingly, while a microscope can offer an immediate, real world benefit in a variety of applications, the same cannot be said for the claimed ESTs. Fisher's proposed analogy is thus inapt. Hence, we conclude that Fisher's asserted uses are insufficient to meet the standard for a “substantial” utility under §101.
Applicant is urged to consider amending the claims such that the claims are drawn to a method that results in a product that unquestionably does have utility under 35 USC 101 and which is adequately supported by the original disclosure.
Claims 1, 5, 7, 9, 21, 24, 29, 34, 58, 116, and 220-227 are also rejected under 35 U.S.C. 112, first paragraph. Specifically, since the claimed invention is not supported by either a specific, substantial, and credible asserted utility or a well-established utility for the reasons set forth above, one skilled in the art clearly would not know how to use the claimed invention.
Response to traversal
At pages 17-19 of the response of 03 November 2025 said representative traverses the rejection of claims under 35 USC 101 as lacking a specific and substantial utility and under 35 USC 112 (a) / first paragraph, for not being enabled. At page 19 of the response said representative asserts:
Moreover, performing spatial analysis of polypeptides (i.e., spatial proteomics) including determining identity/amino acid sequence and location (positional information) of polypeptides within a sample has a specific, substantial, and credible utility based on a “real world” use as recognized by those of ordinary skill in the art.
The above argument has been considered and has not been found to be persuasive towards the withdrawal of the rejection. As presently worded, the claimed method fairly encompasses “analyzing polypeptide” that may be unknown. In support of this interpretation attention is directed to page 15 of the response of 03 November 2025 where applicant asserts:
[T]the methods of the present claims do not rely on the function or structure of a polypeptide since it can be practiced using any polypeptide because there are no specific structural or functional properties the polypeptide is required to have. Accordingly, the specification and claims recite a generic “polypeptide.” In fact, one of the advantages of the claimed method is that the identity of the polypeptide may be unknown before practicing the methods. (Emphasis in original)
Attention is also directed to MPEP 2107.01 I [R-07.2022], which states in part:
B. Substantial Utility
"[A]n application must show that an invention is useful to the public as disclosed in its current form, not that it may prove useful at some future date after further research. Simply put, to satisfy the ‘substantial’ utility requirement, an asserted use must show that the claimed invention has a significant and presently available benefit to the public." Fisher, 421 F.3d at 1371, 76 USPQ2d at 1230. The claims at issue in Fisher were directed to expressed sequence tags (ESTs), which are short nucleotide sequences that can be used to discover what genes and downstream proteins are expressed in a cell. The court held that "the claimed ESTs can be used only to gain further information about the underlying genes and the proteins encoded for by those genes. The claimed ESTs themselves are not an end of [the inventor’s] research effort, but only tools to be used along the way in the search for a practical utility…. [Applicant] does not identify the function for the underlying protein-encoding genes. Absent such identification, we hold that the claimed ESTs have not been researched and understood to the point of providing an immediate, well-defined, real world benefit to the public meriting the grant of a patent." Id. at 1376, 76 USPQ2d at 1233-34). Thus a "substantial utility" defines a "real world" use. Utilities that require or constitute carrying out further research to identify or reasonably confirm a "real world" context of use are not substantial utilities. For example, both a therapeutic method of treating a known or newly discovered disease and an assay method for identifying compounds that themselves have a "substantial utility" define a "real world" context of use. An assay that measures the presence of a material which has a stated correlation to a predisposition to the onset of a particular disease condition would also define a "real world" context of use in identifying potential candidates for preventive measures or further monitoring. On the other hand, the following are examples of situations that require or constitute carrying out further research to identify or reasonably confirm a "real world" context of use and, therefore, do not define "substantial utilities":
(A) Basic research such as studying the properties of the claimed product itself or the mechanisms in which the material is involved;
(B) A method of treating an unspecified disease or condition;
(C) A method of assaying for or identifying a material that itself has no specific and/or substantial utility;
(D) A method of making a material that itself has no specific, substantial, and credible utility; and
(E) A claim to an intermediate product for use in making a final product that has no specific, substantial and credible utility.
Office personnel must be careful not to interpret the phrase "immediate benefit to the public" or similar formulations in other cases to mean that products or services based on the claimed invention must be "currently available" to the public in order to satisfy the utility requirement. See, e.g., Brenner v. Manson, 383 U.S. 519, 534-35, 148 USPQ 689, 695 (1966). Rather, any reasonable use that an applicant has identified for the invention that can be viewed as providing a public benefit should be accepted as sufficient, at least with regard to defining a "substantial" utility.
As evidenced above, the claimed method fairly encompasses the analysis of polypeptides that are unknown and thusly have no know utility. As set forth in the MPEP, “a method of assaying for or identifying a material that itself has no specific and/or substantial utility” do not have a substantial utility. Given such analysis and in the absence of convincing evidence to the contrary, the rejection is maintained.
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM..
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682