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
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because:
In Figure(s) 1, 3C – 3E, and 7A – 7C the reference characters, sheet numbers, and view numbers are not all oriented in the same direction so as to avoid having to rotate the sheet. See 37 CFR 1.84(p)(1).
Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
INFORMATION ON HOW TO EFFECT DRAWING CHANGES
Replacement Drawing Sheets
Drawing changes must be made by presenting replacement sheets which incorporate the desired changes and which comply with 37 CFR 1.84. An explanation of the changes made must be presented either in the drawing amendments section, or remarks, section of the amendment paper. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). A replacement sheet must include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of the amended drawing(s) must not be labeled as “amended.” If the changes to the drawing figure(s) are not accepted by the examiner, applicant will be notified of any required corrective action in the next Office action. No further drawing submission will be required, unless applicant is notified.
Identifying indicia, if provided, should include the title of the invention, inventor’s name, and application number, or docket number (if any) if an application number has not been assigned to the application. If this information is provided, it must be placed on the front of each sheet and within the top margin.
Annotated Drawing Sheets
A marked-up copy of any amended drawing figure, including annotations indicating the changes made, are required by the examiner. The annotated drawing sheet(s) must be clearly labeled as “Annotated Sheet” and must be presented in the amendment or remarks section that explains the change(s) to the drawings.
Timing of Corrections
Applicant is required to submit acceptable corrected drawings within the time period set in the Office action. See 37 CFR 1.85(a). Failure to take corrective action within the set period will result in ABANDONMENT of the application.
If corrected drawings are required in a Notice of Allowability (PTOL-37), the new drawings MUST be filed within the THREE MONTH shortened statutory period set for reply in the “Notice of Allowability.” Extensions of time may NOT be obtained under the provisions of 37 CFR 1.136 for filing the corrected drawings after the mailing of a Notice of Allowability.
Specification
The disclosure is objected to because of the following informalities:
The use of the term TWEEN, which is a trade name or a mark used in commerce, has been noted in this application. See page 68, line 11; and page 70, line 9. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
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, 2, 8-12, 17, 21, 24, 35, 39, 43, 44, 57, 58, 61, and 71 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, 2, and 11 are indefinite with respect to which type(s) of “nucleic acid” (target/analyte) and “biological sample” from which organism(s) is / are encompassed by the claim.
The term “substantially complementary” in claims 1, 2, and 11 is a relative term which renders the claims indefinite. The term “substantially complementary” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 1, 2, 11, 17, 21, 24, and 35 are indefinite with respect to what constitutes the metes and bounds of an oligonucleotide, e.g., a padlock oligonucleotide. A review of the disclosure fails to find where applicant has provided a closed definition for the term “oligonucleotide,” and a review of the art finds that there is not a single art-accepted definition. In support of this position, it is noted that Merriam-Webster.com (“Oligonucleotide definition,” Merriam-Webster.com; accessed 08-23-2017) provides the following exemplary definition:
[A] short nucleic-acid chain usually consisting of up to approximately 20 nucleotides. (Emphasis added)
US 2019/0002971 A1 (Kslover et al.), paragraph [0084], teaches:
In some embodiments, binding moieties comprise an oligonucleotide or analog thereof having a length in the range of from 6 to 60 nucleotides.
US 2009/0011943 A1 (Drmanac et al.), at paragraph [0116], teaches:
The length of capture oligonucleotides may vary widely, In one aspect, capture oligonucleotides and their complements in a bridging oligonucleotide have lengths in the range of from 10 to 100 nucleotides; and more preferably, in the range of from 10 to 40 nucleotides. (Emphasis added)
In comparison, US Patent 6,444,661 B1 (Barton et al.), column 6, first paragraph, states:
The probe oligonucleotide can be as short as about 8-10 bases, up to a length of several thousand bases: the probe can be as long or longer than the target polynucleotide. (Emphasis added)
“Oligonucleotide”, Wikipedia.com (accessed February 17, 2019) teaches:
A less than 100% yield of each synthetic step and the occurrence of side reactions set practical limits of the efficiency of the process so that the maximum length of synthetic oligonucleotides hardly exceeds 200 nucleotide residues. (Emphasis added)
When as here it is evident that there is not a single art-accepted meaning for the term, a question as to the metes and bounds of the claim exist.
The term “adjacent” in claim 1 is a relative term which renders the claim indefinite. The term “adjacent” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The term “plurality” in claims 1, 2, 11, and 61 is a relative term which renders the claims indefinite. The term “plurality” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 11 is indefinite with respect to what constitutes the metes and bounds of “a protein”.
Claims 8-10, 17, 21, 24, 35, 39, 43-44, 57-58, and 71, which depend from claim 1; and claim 12, which depends from claim 11, fail to overcome the above identified issues and are similarly rejected.
Claim 9 is indefinite with respect to which type(s) of RNA, from which sources/organisms is/are encompassed by the claim. In support of this position attention is directed to US 2005/0058982 A1 (Han et al.), which teaches at paragraph [0030]:
Therefore, RNA may be double-stranded (dsRNA), single-stranded (ssRNA) or double-stranded with a single-stranded overhang. Common types of RNA include messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), short interfering RNA (siRNA), micro RNA (miRNA) and small hairpin RNA (shRNA), each of which plays a specific role in biological cells.
If, per chance, the RNA is that in a virus, claim 9 is indefinite with respect to just which forms/source(s) of viral RNA are encompassed. In support of this position attention is directed to US 6,017,923 (Sabol et al.), which teaches at column 34, paragraph 4, “…RNA viruses such as, but not limited to, influenza type A, B, and C, mumps, measles, rhinovirus, dengue, rubella, rabies, hepatitis virus A, encephalitis virus, and the like…”
Claim 11 is indefinite with respect to what constitutes the metes and bounds of “a biological sample”, “an analyte binding moiety that binds specifically to the protein”, “a capture probe” and its “analyte capture sequence”. For example, is the “analyte binding moiety that binds specifically to the protein” a nucleic acid (DNA) sequence, e.g., an aptamer, or is it part of an antibody or is it something else entirely?
Claim 57 is indefinite with respect to what constitutes the metes and bounds of the “sample”, be it “a formalin-fixed, paraffin-embedded (FFPE) sample or fresh frozen sample.” For example, what type(s) of “samples” from which organisms(s) is/are encompassed by the claim.
Claim 58 is indefinite with respect to what constitutes the metes and bounds of “a tissue section.” More specifically, which type(s) of tissue(s) from which organism(s) is/are encompassed by the claim?
The term “more” in claims 12, 24, and 61 is a relative term which renders the claims indefinite. The term “more” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim Rejections - 35 USC § 112, Enablement
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 1-2, 8-12, 17, 21, 24, 35, 39, 43-44, 57-58, 61, and 71 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the full breadth of the claimed invention.
Standard for Enablement
It is well settled that in order to satisfy the enablement requirement, “the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 [42 USPQ2d 1001] (Fed. Cir. 1997). (Emphasis added)
For purposes of examination, the aspect of just what constitutes the “full scope” of the claims is that which is consistent with the broadest reasonable interpretation. See MPEP 904.01 and 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.
As set forth in the unanimous U.S. Supreme Court decision in Amgen Inc., et al. v. Sanofi et al. 598 U.S. ___ (2023):
Our decisions in Morse, Incandescent Lamp, and Holland Furniture reinforce the simple
statutory command. If a patent claims an entire class of processes, machines,
manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. See §112(a); see also Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U. S. 405, 419 (1908) (“[T]he claims measure the invention.”). (Emphasis added)
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To be fair, Amgen does not dispute this much. It freely admits that it seeks to claim for
itself an entire universe of antibodies. Still, it says, its broad claims are enabled because scientists can make and use every undisclosed but functional antibody if they simply follow the company’s “roadmap” or its proposal for “conservative substitution.” We cannot agree. These two approaches amount to little more than two research assignments… Whether methods like a “roadmap” or “conservative substitution” might suffice to enable other claims in other patents—perhaps because, as this Court suggested in Incandescent Lamp, the inventor identifies a quality common to every functional embodiment, supra, at 13—they do not here. They leave a scientist about where Sawyer and Man left Edison: forced to engage in “painstaking experimentation” to see what works. 159 U. S., at 475. That is not enablement. More nearly, it is “a hunting license.” Brenner v. Manson, 383 U. S. 519, 536 (1966). (Emphasis added)
It is further noted that “routine experimentation is ‘not without bounds.’” Wyeth v. Abbott Laboratories 107 USPQ2d 1273, 1275, 1276 (Fed. Cir. June 2013), citing Cephalon, Inc. v. Watson Pharm., Inc., 707 F.3d 1330, 1339 [105 USPQ2d 1817] (Fed. Cir. 2013), and that what constitutes "undue experimentation" can be evaluated from the perspective of the amount of time required to enable the full scope of the invention. In support of this position, attention is directed to Cephalon at 1823, citing White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 218 USPQ 961 (Fed. Cir. 1983), that work that would require 18 months to 2 years so to enable the full scope of an invention, even if routine, would constitute undue experimentation. As stated therein:
Permissible experimentation is, nevertheless, not without bounds. This court has held that experimentation was unreasonable, for example, where it was found that eighteen months to two years’ work was required to practice the patented invention. See, e.g., White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d 788, 791 [218 USPQ 961] Fed. Cir.1983). (Emphasis added)
As set forth in Cephalon Inc. v. Watson Pharmaceuticals Inc. 105 USPQ2d 1817, 1821 (CAFC, 2013):
The following factors may be considered when determining if a disclosure requires undue experimentation:
(1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
Wands, 858 F.2d at 737 (“Wands factors”); Enzo Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362, 1372 [52 USPQ2d 1129] (Fed. Cir. 1999) (“The Wands factors, when applied from the proper temporal perspective … are a useful methodology for determining enablement….”). These factors while illustrative are not mandatory. Enzo Biochem, Inc., 188 F.3d at 1371. What is relevant depends on the facts, and although experimentation must not be undue, a reasonable amount of routine experimentation required to practice a claimed invention does not violate the enablement requirement. Id.
Holding and Rationale
Claims 1-2, 8-12, 17, 21, 24, 35, 39, 43-4, 57-58, 61, and 71 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Nature of the Invention
Claims 1, 2, 11, and 61 are the only independent claims pending. Claims 1, 9-12, 24, 44, and 61 are deemed to be representative and, for convenience, are reproduced below.
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As evidenced above in claim 1, one is to analyze the nucleic acid found in “a biological sample”. Said biological sample has been construed as encompassing any form of “a biological sample” where the nucleic acid (target) is that found in any organism, including any mammal, fish, virus, bacteria, or plant.
As evidenced above, the method of claim 1 requires the use of “a plurality of capture probes… [which[ comprises a capture domain and a blocking moiety at its 3’ end”. Said method also requires the use of “a padlock probe”, which comprises “a first sequence” and a “second sequence” which are “substantially complementary” to a first and second portion of the “nucleic acid”, respectively.
As seen in dependent claims 8 and 9, the “nucleic acid” target is either DNA (claim 8) or an “RNA”, which, in claim 10 “is mRNA.”
As specified in claim 11, the method is to result with “identifying a location of a protein in a biological sample”. Applicant, at page 6, third paragraph, provides the following description of types of proteins.
In some instances, the analyte is selected from of a lipid, a carbohydrate, a peptide, a
protein, a glycoproteins (N-linked or O-linked), a lipoprotein, a phosphoprotein, a specific phosphorylated or acetylated variants of a protein, a amidation variant of a protein, a hydroxylation variants of a protein, a methylation variant of a protein, a ubiquitylation variant of a proteins, a sulfation variant of a protein, a viral coat protein, an extracellular protein, an intracellular protein, an antibody, an antigen binding fragment, or any combination thereof. In some instances, the analyte is a protein. (Emphasis added)
As seen in claim 24, one must have primers that will hybridize “to the circularized padlock oligonucleotide”.
As seen in claim 44, “the capture probe is affixed to the substrate at a 5’ end of the capture probe.”
As seen in claim 61, it is to “a kit” and can comprise any number of “padlock oligonucleotides, primer and substrate with “capture probes”.
The breadth of the claims
The “nucleic acid” that the capture probes and padlock probes are to bind to has been construed as encompassing any DNA and RNA, including mRNA, found in any organism.
Attention is directed to the following publications which teach of the enormity of the subphylum Vertebrata as well as 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.
“Vertebrate” (Wikipedia.com, accessed 04 September 2025) teaches:
Vertebrates (j'v3:rtabrit, - ~~.!!D, also called Craniates, are animals with a vertebral column and a cranium. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain.
The vertebrates make up the sub hylum Vertebrata ({ V3:rta'bre,ta/ VUR-ta-BRAY-ta) with some 65,000 species, by far the largest ranked grouping in the phylum Chordata. The vertebrates include mammals, birds, amphibians, and various classes of fish and reptiles. (Emphasis added)
“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)
Attention is directed to “Eukaryotic Genome Complexity” (Pray, Nature Education, 1(1):36, 2008, pages 1-4.). As seen therein, a table of estimated protein encoding genes in different genomes is provided.
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As evidenced above in claims 1, 9 and 10, the claimed method and kit requires the presence and use of both capture probes and padlock oligonucleotides that will bind to three different sequences in the “nucleic acid”, be it DNA, RNA or mRNA. As seen in claim 11, the method is to result with “identifying a location of a protein in a biological sample”. As seen therein, one is to employ not only a “capture probe” but “an analyte binding moiety that binds specifically to the protein”.
The Predictability or Unpredictability of the Art
The nucleotide sequence for the genome of any given species of bacteria, much less any and all other organisms, is highly unpredictable. It is also highly unpredictable as to just which nucleotide sequenes will bind to proteins found in any organism in any “biological sample”.
In order to enable the full scope of the invention, one would have to determine the nucleotide sequence for each and every organism, much less any gene of interest, in order to identify the correct nucleotide sequences for all “capture probes” and the first and second sequences of the padlock oligonucleotide as wel as the primers, all of which are encompassed by the claimed kit.
The Presence of Absence of Working Examples
The disclosure has been found to comprise the following prophetic examples:
“EXAMPLE 1 - Method for identifying the location of mRNA molecules using RCA and digestion”, page 67;
“EXAMPLE 2 - Digestion of the Amplified Padlock Oligonucleotide and a second RCA reaction”, page 69; and
“EXAMPLE 3 - Method for identifying a location of an RTL ligation product using RCA and detection probes”, page 71.
The disclosure has not been found to comprise and provide a Sequence Listing where the nucleotide sequence of any target nucleic acid or target protein, as well as the nucleotide sequence for any primer, capture probe or “padlock oligonucleotide” for any sequence in any organism found in any “biological sample”.
The State of the Prior Art
As evidenced above, it is estimated that there are many tens of millions of different species of bacteria. “List of sequenced bacterial genomes” (Wikipedia.com; accessed 24 January 2014) teaches that less than 300 different species of bacteria have had their genomes sequenced, which comprises species found in some 8 genera of cyanobacterium.
The lack of guidance and quantity of experimentation necessary
The quantity of experimentation necessary is great, on the order of many man-years, and then with little if any reasonable expectation of successfully enabling the full scope of the claims. In support of this position, it is noted that the claimed method requires the pairing of probes/primers with template. In order to select the appropriate probe/primers, which are deemed to be essential, one must have knowledge of the nucleotide sequence of the template. Neither the as-filed specification nor the state of the art provides such guidance so that one skilled in the art, without any undue experimentation, could reasonably generate such a probe system contemplated by the intended breadth of the claimed method. Absent knowledge of the nucleotide sequence of the template, selection of the correct primer is highly unpredictable.
Time required to enable a portion of the claims’ scope.
If one were to use a probe/primer that is but 20 nucleotides long, and substituting each position with the four traditional nucleotides, there are some 420 or 1.099 x 1012 or 1,099,000,000,000 different potential probes from which to select. If one could somehow produce and screen 100 million (100,000,000) 20mer oligonucleotides a week, and to do so for 52 weeks a year, it would take over 211 years to screen for useful primers of this one size for one target. Such a tremendous effort constitutes undue experimentation.
In order to determine the appropriate probes/primers for the millions of organisms encompassed by the claimed method, one would need to determine the nucleotide sequence of the various target sequences. “How many species of bacteria are there?” teaches that it would take “a few months” to determine the nucleotide sequence of any given bacteria. As stated therein:
Today, given that sequencing a bacterial genome costs half a million US dollars and takes a few months, this is infeasible. (Emphasis added)
Assuming, arguendo, that one needed to sequence but only 200 bacteria, and it took on average just 3 months to sequence one strain of one species of bacteria, it would take some 600 months, or 50 years to sequence just 1 strain from each of 200 different species of bacteria. Such effort is deemed to constitute undue experimentation.
Alternatively, if one were to determine the nucleotide sequence of the genome of an organism every day, 365 days a year, and to also identify in the same day probes/primers that would be useful in the identification of target sequence(s) found in said organism wherein said target sequence(s) has/have utility under 35 USC 101, it would take approximately 2739 years to sequence even 1 million bacteria, viruses or fungi. Clearly, such an effort to enable the full scope of that claimed would constitute undue experimentation.
As presently worded, the claimed method fairly encompasses the many species of cyanobacterium encompassed by the 150 genera of cyanobacterium at issue in Vaeck. “List of sequenced bacterial genomes” (Wikipedia.com; accessed 24 January 2014) teaches that the genomic sequence of less than 300 species of bacteria has been determined, and that these include some 17 strains of cyanobacterium, which are limited to but 8 genera. By comparison, in Vaeck, 9 genera of cyanobacterium had been disclosed, yet it was held that to enable the full scope of the invention which was limited to the 150 genera of cyanobacterium, it would require undue experimentation.
Attention is also directed to MPEP 2164.06(b) and In re Vaeck, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991).
Where, as here, a claimed genus represents a diverse and relatively poorly understood group of microorganisms, the required level of disclosure will be greater than, for example, the disclosure of an invention involving a “predictable” factor such as a mechanical or electrical element. See Fisher, 427 F.2d at 839, 166 USPQ at 24.
Attention is also directed to the decision in Promega Corp. v. Life Techs. Corp. 113 USPQ2d 1181, 1187, 1189 (Fed. Cir. 2014):
The enablement requirement ensures that “the public knowledge is enriched by the patent specification to a degree at least commensurate with the scope of the claims.” Nat'l Recovery Techs., Inc. v. Magnetic Separation Sys., Inc., 166 F.3d 1190, 1195-96 [49 USPQ2d 1671] (Fed. Cir. 1999). The scope of the claims must be “less than or equal to the scope of enablement.” Id. at 1196.
[1] Here, we disagree with Promega's characterization that unrecited STR loci combinations in the “open loci set” limitation of the asserted claims are merely “unrecited elements”; under the undisputed claim construction, they are part of the claim scope.
***
While the claims of the
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patents are not directed to a genus of compounds as in Wyeth, the claims at issue here similarly cover potentially thousands of undisclosed embodiments in an unpredictable field. And similar to Wyeth, the specification of the
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patents provides only a starting point—specific STR loci combinations that successfully co-amplify—with no disclosure that would have allowed a skilled artisan, absent laborious testing, to add new loci to these recited STR loci combinations that would still successfully co-amplify. Undue experimentation is a matter of degree, and even “a considerable amount of experimentation is permissible,” so long as it is “merely routine” or the specification “provides a reasonable amount of guidance” regarding the direction of experimentation. Johns Hopkins Univ. v. CellPro, Inc., 152 F.3d 1342, 1360-61 [47 USPQ2d 1705] (Fed. Cir. 1998) (internal quotation omitted). But permissible routine experimentation “is not without bounds.” Wyeth, 720 F.3d at 1386 (citation omitted). As the extensive evidence here demonstrates, undue experimentation would have been required in order to enable the full scope of coverage sought by
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— the successful co-amplification of potentially thousands of unrecited STR loci combinations. (Emphasis added)
In view of such legal precedence, the aspect of having to work for many tens of years just to provide the starting materials for minute fraction of the scope of the claimed invention is deemed to constitute both an unreasonable length of time and undue experimentation.
In view of the breadth of scope clamed, the limited guidance provided, the unpredictable nature of the art to which the claimed invention is directed, and in the absence of convincing evidence to the contrary, the claims are deemed to be non-enabled by the disclosure.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-2, 8-12, 17, 21, 24, 35, 39, 43-4, 57-58, 61, and 71 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 enablement requirement.
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 difficul