DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Claims 21-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 19 November 2021.
Drawings
The drawings were received on 25 July 2023. 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
PNG
media_image1.png
18
19
media_image1.png
Greyscale
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.”
***
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, 8-9, 20, and 28-30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite with respect to what constitutes the metes and bounds of “a monoclonal antibody”. In support of this position attention is directed to US 5,945,293 (Siiman et al.), at column 5, third paragraph, teaches:
"Antibody" is defined to include polyclonal antibodies from any native source, and native or recombinant monoclonal antibodies of classes IgG, IgM, IgA, IgD, and IgE, hybrid derivatives, humanized or chimeric antibodies, and fragments of antibodies including Fab, Fab', and F(ab')2.
It is further noted that it is unclear as to which organism(s) is/are used as a source of cells that produce the monoclonal antibody. 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)
Claim 1 is indefinite with respect to what length, or range of lengths, each of the components of the “plurality of barcodes [which] comprises a molecular label sequence and an oligo(dT) target-binding region” can have.
The newly-added limitation of “an oligo(dT)” has been construed as encompassing an oligonucleotide that comprises only T residues. 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.
Claims 2, 8-9, 20, and 28-30, which depend from claim 1, fail to overcome these issues and are similarly rejected.
Response to traversal
Applicant’s representative, at pages 5-7 of the response of 01 October 2025, hereinafter the response, traverses the rejection of claims under 35 USC 112, second paragraph / (b). As indicated therein, the aspect of amending the claims so to recite both “monoclonal” antibodies and “oligo(dT)” was done so to overcome prior rejections. As indicated above, the prior rejections have been replaced with new rejections that are directed to the newly added claim language. Given such, and in the absence of convincing evidence to the contrary, claims 1-2, 8-9, 20, and 28-30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 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, 8-9, 20, and 28-30 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.
As set forth in Cephalon Inc. v. Watson Pharmaceuticals Inc. 105 USPQ2d 1817, 1821 (CAFC, 2013):
To satisfy section 112 of the 1952 Patent Act, the specification must enable a person of ordinary skill in the art to make and use the invention. 35 U.S.C. § 112, ¶1. This requirement is met when at the time of filing the application one skilled in the art, having read the specification, could practice the invention without “undue experimentation.” In re Wands, 858 F.2d 731, 736-37 [8 USPQ2d 1400] (Fed. Cir. 1988). Whether undue experimentation is required “is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” ALZA Corp. v. Andrx Pharms., LLC, 603 F.3d 935, 940 [94 USPQ2d 1823] (Fed. Cir. 2010) (citing Wands, 858 F.2d at 737).
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. The burden of proof here is on Watson to show that the Khankari patents are invalid for lack of enablement by clear and convincing evidence. See Auto. Tech. Int'l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 1281 [84 USPQ2d 1109] (Fed. Cir. 2007).
Additionally, 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 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.”).
The Nature of the Invention, The breadth of the claims, & The state of the prior art
Claim 1 is the only independent claim pending. Claims 1, 20, and 28 are deemed to be representative and, for convenience, are reproduced below.
PNG
media_image2.png
483
547
media_image2.png
Greyscale
PNG
media_image3.png
70
540
media_image3.png
Greyscale
PNG
media_image4.png
94
545
media_image4.png
Greyscale
As evidenced above, in claim 1 the “plurality of cells” has been limited to human cells. However, as seen in paragraph [0250], the cells can be infected with a variety of organisms. As stated therein:
[0250] In some embodiments, the cells are cells that have been infected with virus
and contain viral oligonucleotides. In some embodiments, the viral infection can be caused by a virus such as single-stranded (+ strand or "sense") DNA viruses (e.g. parvoviruses), or double-stranded RNA viruses (e.g. reoviruses). (Emphasis added)
As a result of amendment, claim 1 now recites the limitation of:
barcoding copies of a nucleic acid target in the plurality of nuclei using the plurality of barcodes to generate a plurality of barcoded nucleic acid molecules,
wherein each of the plurality of barcodes comprises a molecular label sequence and [[a]] an oligo(dT) target-binding region, and
wherein the molecular label sequences of at least two barcodes of the plurality of barcodes comprise different sequences[.] (Emphasis added)
It stands to reason that any and all mRNA copies will have a polyA sequence, to which the “oligo(dT) target binding region” would hybridize. With mRNA transcripts from different genes all having a polyA sequence, one would not be able to determine how many copies of a specific target are present as it would be binding all mRNA transcripts of all genes.
To the degree that the cells are human cells, and that the target can be a human sequence, it is noted that the last human chromosome to be sequenced was the Y chromosome, and that its nucleotide sequence was not published until 14 September 2023 (“The complete sequence of a human Y chromosome”, Nature, volume 621, 344. 14 September 2023.) As stated therein in the abstract:
The human Y chromosome has been notoriously difficult to sequence and assemble
because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZ and RBMY; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region.
It is noted that the subject application was filed on 29 July 2019, and has a priority date of 03 August 2018. It is noted that both of the filing and priority dates predate the determination of the complete human sequence by 5 years. Such amount of time has been held to be unreasonable in determining whether full enablement has been reached.
Applicant, at page 91, paragraph [0255], teaches:
For example, the nucleic acid target molecules and/or the undesirable nucleic acid species
can comprise DNA molecules, RNA molecules, genomic DNA molecules, cDNA molecules, mRNA molecules, rRNA molecules, mtDNA, siRNA molecules, or any combination thereof. The nucleic acid target molecule can be double-stranded or single-stranded. In some embodiments, the plurality of nucleic acid target molecules can comprise nucleic acids derived from one or more non-nuclear organelles. In some embodiments, the plurality of nucleic acid target molecules can comprise polyA RNA molecules. In some embodiments, the plurality of nucleic acid target molecules comprise at least 100, at least 1,000, at least 10,000, at least 20,000, at least 30,000, at least 40,000, at least 50,000, at least 100,000, at least 1,000,000, or more nucleic acid species. (Emphasis added)
A review of the disclosure fails to find where any Sequence Listing has been provided, much less provide the sequence of the human genome, and lesser still the nucleotide sequence for any virus or bacteria that may be infecting a human cell, e.g., the coronavirus responsible for the COVID-19 pandemic.
In addition to the above, it is also noted that a review of the disclosure fails to find where applicant has identified epitopes of the “nuclear pore complex’ that are unique to the “nuclear pore complex”. Said disclosure has also not been found to specify the type(s) and source(s) of the requisite monoclonal antibodies, much less provide the requisite “monoclonal antibody capable of binding a nuclear pore complex”. Given such, the claimed method has been construed as encompassing any and all types of monoclonal antibodies, produced by any known source.
Attention is directed to US 5,945,293 (Siiman et al.), at column 5, third paragraph, teaches:
"Antibody" is defined to include polyclonal antibodies from any native source, and native or recombinant monoclonal antibodies of classes IgG, IgM, IgA, IgD, and IgE, hybrid derivatives, humanized or chimeric antibodies, and fragments of antibodies including Fab, Fab', and F(ab')2.
It is further noted that it is unclear as to which organism(s) is/are used as a source of cells that produce the monoclonal antibody. 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)
The 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 nucleic acids to be determined can be in excess of 1,000,000.
As seen in amended claim 1, “the nuclei-binding reagent is a monoclonal antibody capable of binding a nuclear pore complex”. The epitope(s) are undefined as are the types and sources of monoclonal antibodies.
Attention is directed to US 5,888,727 (Lund et al.), at column 1, third paragraph, teach:
The transport of macromolecules through the nuclear envelope is a complex process that involves many protein factors and an energy source such as GTP (see E. Izaurralde and I.W. Mattaj, Cell 81:153, 1995 and D. Gorlich, et al., Science 271:1513, 1996 for review). Besides the many components of the nuclear pore complex (NPC), several soluble proteins localized to one or both sides of the nuclear envelope are also essential. (Emphasis added)
Attention is also directed to US 2009/0203043 A1 (Hornbeck et al.), at paragraph [0063], teach:
[0063] NUP93, phosphorylated at Thr49, is among the proteins listed in this patent. NUP93 (Nucleoporin 93) is a nuclear pore protein required for correct nuclear pore assembly. The nuclear pore complex, comprised of approximately 30 nucleoporins, mediates the exchange of macromolecules across the nuclear envelope. (PhosphoSite.RTM., Cell Signaling Technology (Danvers, Mass.), Human PSD.TM., Biobase Corporation, (Beverly, Mass.)). (Emphasis added)
Attention is directed to “Monoclonal Antibody Production”, Icosagen.com, accessed 04/17/2014. As is disclosed therein, it would take on the order of 3-4 months for immunization, and an additional 2-3 months for hybridoma production. In short, it would take on the order of 5 to 7 months to produce a single monoclonal antibody in a mouse.
As seen in Hornbeck et al., there are some 30 nucleoproteins in a nuclear pore complex. If one were to produce a single monoclonal antibody for each of the 30 nucleoproteins, it would take on the order of 150 months 12.5 years) to 210 months (17.5 years) to produce a single monoclonal antibody for each of the 30 nucleoproteins that are in a nuclear pore complex.
Clearly, such an effort to enable the full scope of that claimed would constitute undue experimentation. In support of this position attention is directed to Cephalon, 1823:
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). Likewise, we have held that the amount of experimentation would be undue where: (1) the specification lacks guidance by teaching away from the subject matter that was eventually claimed; and (2) there is evidence of the patentee's own failures to make and use the later claimed invention at the time of the application. See, e.g., AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244 [68 USPQ2d 1280] (Fed. Cir. 2003)
The amount of direction or guidance presented,
The amount of guidance provided is limited, generally prophetic, and not commensurate with the scope of the claims.
The presence or absence of working examples
The disclosure has been found to comprise 2 prophetic examples, neither of which identifies any epitope on any component of the nuclear pore complex, much less the nucleotide sequence of any probe or target nucleic acid, be it DNA or RNA.
The predictability or unpredictability of the art
As noted in In re Fisher 166 USPQ 18 (CCPA, 1970):
In cases involving predictable factors, such as that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws. In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.
In the present case, the nucleotide sequence of the target nucleic acids, and the amino acid sequences and epitopes of the components of the “nuclear pore complex”, mu h less the amino acid sequences of the genus of antibodies that are “capable of specifically binding a nuclear pore complex” are highly unpredictable.
Attention is also directed to Wyeth v. Abbott Laboratories 107 USPQ2d 1273 (Fed. Cir. June 2013):
The remaining question is whether having to synthesize and screen each of at least tens of thousands of candidate compounds constitutes undue experimentation. We hold that it does. Undue experimentation is a matter of degree. Chiron Corp. v. Genentech, Inc., 363 F.3d 1247, 1253 [70 USPQ2d 1321] (Fed. Cir. 2004) (internal quotation omitted). Even “a considerable amount of experimentation is permissible,” as 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). Yet, routine experimentation is “not without bounds.” Cephalon, Inc. v. Watson Pharm., Inc., 707 F.3d 1330, 1339 [105 USPQ2d 1817] (Fed. Cir. 2013).
Our cases have described limits on permissible experimentation in the context of enablement. For example, in ALZA Corp. v. Andrx Pharmaceuticals, LLC, we affirmed a judgment of nonenablement where the specification provided “only a starting point, a direction for further research.” 603 F.3d 935, 941 [94 USPQ2d 1823] (Fed. Cir. 2010) (internal quotation omitted). We concluded that one of ordinary skill “would have been required to engage in an iterative, trial-and-error process to practice the claimed invention even with the help of the … specification.” Id. at 943. In Cephalon, although we ultimately reversed a finding of nonenablement, we noted that the defendant had not established that required experimentation “would be excessive, e.g., that it would involve testing for an unreasonable length of time.” 707 F.3d at 1339 (citing White Consol. Indus., Inc. v. Vega Servo-Control, Inc., 713 F.2d 788, 791 [218 USPQ 961] (Fed. Cir. 1983)). Finally, in In re Vaeck, we affirmed the PTO's nonenablement rejection of claims reciting heterologous gene expression in as many as 150 genera of cyanobacteria. 947 F.2d 488, 495-96 [20 USPQ2d 1438] (Fed. Cir. 1991). The specification disclosed only nine genera, despite cyanobacteria being a “diverse and relatively poorly understood group of microorganisms,” with unpredictable heterologous gene expression. Id. at 496.
Here, the specification similarly discloses only a starting point for further iterative research in an unpredictable and poorly understood field. Synthesizing candidate compounds derived from sirolimus could, itself, require a complicated and lengthy series of experiments in synthetic organic chemistry. Even putting the challenges of synthesis aside, one of ordinary skill would need to assay each of at least tens of thousands of candidates. Wyeth's expert conceded that it would take technicians weeks to complete each of these assays. The specification offers no guidance or predictions about particular substitutions that might preserve the immunosuppressive and antirestenotic effects observed in sirolimus. The resulting need to engage in a systematic screening process for each of the many rapamycin candidate compounds is excessive experimentation. We thus hold that there is no genuine dispute that practicing the full scope of the claims, measured at the filing date, required 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, 8-9, 20, and 28-30 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.
Response to argument
At pages 7-10 of the response said representative traverses the rejection of claims under 35 USC 112 first paragraph / (a for not satisfying the enablement requirement. At page 9 of the response said representative asserts:
Applicant respectfully disagrees with the enablement rejections. However, solely to expedite prosecution, claim 1 has been amended recite, in part, "wherein the nuclei-binding reagent is a monoclonal antibody." Applicant submits that many of the elements that the Office Action is concerned about, e.g., "the Y chromosome" and "the nucleotide sequence for any virus or bacteria that may be infecting a human cell, e.g., the coronavirus responsible for the COVID- 19 pandemic," are not explicitly recited in the claims. As such, the Office Action's argument is improperly directed to the instant claims. In attempting to establish this rejection, the Office Action appears to select elements that are at the periphery of the claim (e.g., COVID-19), and then argues that the Applicant does not adequately enable such elements. However, the law does not require every species of a claim be enabled. See, e.g., In re Angstadt, 537 F.2d 498, 502-03, 190 U.S.P.Q. (BNA) 214, 218, (C.C.P.A. 1976).
The above argument has been considered and has not been found persuasive.
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.
As a result of amendment, the claimed method encompasses the use of any “monoclonal antibody capable of binding a nuclear pore complex” in “huma cells”. The type of “monoclonal antibody” is not limited, and thusly, has been construed as encompassing any monoclonal antibody.
Attention is directed to US 5,945,293 (Siiman et al.), at column 5, third paragraph, teaches:
"Antibody" is defined to include polyclonal antibodies from any native source, and native or recombinant monoclonal antibodies of classes IgG, IgM, IgA, IgD, and IgE, hybrid derivatives, humanized or chimeric antibodies, and fragments of antibodies including Fab, Fab', and F(ab')2.
It is further noted that it is unclear as to which organism(s) is/are used as a source of cells that produce the monoclonal antibody. 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)
Attention is directed to US 4,939,082 (Naujoks et al.), which teaches in the abstract:
The monoclonal antibody is preferably produced by immunizing a host animal with an immunogen containing aluminum hydroxide, Bordatella pertussis and native saliva alpha amylase at least 7 times over a period of at least 9 months, fusing B lymphocytes of the immunized host animal with a transforming agent to produce hybridomas, cloning and culturing the hybridomas, and screening antibodies formed. (Emphasis added)
As evidenced above, it would take on the order of 9 months just to immunize the host animal. Assuming, arguendo, that one were to produce just two monoclonal antibodies, such would take on the order of 18 months, which has been held to constitute undue experimentation. 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)
At page 9 of the response said representative asserts:
However, the law does not require every species of a claim be enabled. See, e.g., In re Angstadt, 537 F.2d 498, 502-03, 190 U.S.P.Q. (BNA) 214, 218, (C.C.P.A. 1976).
The above argument has been considered and has not been found persuasive. In support of this position attention is directed to 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)
It is noted that the unanimous decision of the US Supreme Court controls over that of the CCPA.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-2, 8-9, 20, and 28-30 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 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.
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.
Acknowledgement is made of the fact that the claims are to a method and not to a product. However, it is well settled that in order to satisfy the written description for a method, one must also disclose the molecules required to perform the method. In support of this position attention is directed to University of Rochester v. G.D. Searle & Co. 68 USPQ2D 1424 (W.D.N.Y. 2003) at 1433 (affirmed; University of Rochester v. G.D. Searle & Co. 69 USPQ2d 1886 (Fed. Cir. 2004)):
Plaintiff also argues that the requirements for written descriptions of claims to chemical compounds are irrelevant to this case because the '850 patent does not claim a compound, but a method of treatment by targeting PGHS-2 activity over PGHS-1 activity. Virtually any compound claim could be transformed into a method claim, however, simply by means of wording the claim in terms of a method of using the compound. With respect to the issue before the Court, then, this is little more than a semantic distinction without a difference. The claimed method depends upon finding a compound that selectively inhibits PGHS-2 activity. Without such a compound, it is impossible to practice the claimed method of treatment. It means little to “invent” a method if one does not have possession of a substance that is essential to practicing that method. Without that substance, the claimed invention is more theoretical than real; it is, as defendants argue, akin to “inventing” a cure for cancer by utilizing a substance that attacks and destroys cancer cells while leaving healthy cells alone. Without possession of such a substance, such a “cure” is illusory, and there is no meaningful possession of the method.
***
What the inventors did not do, however, is succeed in taking the last, critical step of actually isolating such a compound, or at least of developing a process through which one skilled in the art would be directly led to such a compound. Absent that step, their discoveries, valuable though they might have been, did not blossom into a full-fledged, complete invention. Scientific discoveries, and theories based on those discoveries, frequently lay the groundwork for later inventions, but that does not make the discoverer the inventor as well.
Attention is also directed to the decision in Ariad Pharmaceuticals Inc. v. Eli Lilly & Co.
(Fed. Cir. 2010) 94 USPQ2d 1161, 1175, which teaches:
In accordance with Rochester, the ?516 patent must adequately describe the claimed methods for reducing NF-?B activity, including adequate description of the molecules that Ariad admits are necessary to perform the methods. (Emphasis added)
Holding and Rationale
Claims 1-2, 8-9, 20, and 28-30 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.
Claim 1 is the only independent claim pending. Claims 1, 20, and 28 are deemed to be representative and, for convenience, are reproduced below.
PNG
media_image2.png
483
547
media_image2.png
Greyscale
PNG
media_image3.png
70
540
media_image3.png
Greyscale
PNG
media_image4.png
94
545
media_image4.png
Greyscale
As evidenced above, in claim 1 the “plurality of cells” has been limited to human cells. However, as seen in paragraph [0250], the cells can be infected with a variety of organisms. As stated therein:
[0250] In some embodiments, the cells are cells that have been infected with virus
and contain viral oligonucleotides. In some embodiments, the viral infection can be caused by a virus such as single-stranded(+ strand or "sense") DNA viruses (e.g. parvoviruses), or double-stranded RNA viruses (e.g. reoviruses). (Emphasis added)
To the degree that the cells are human cells, and that the target can be a human sequence, it is noted that the last human chromosome to be sequenced was the Y chromosome, and that its sequence was not published until 14 September 2023 (“The complete sequence of a human Y chromosome”, Nature, volume 621, 344. 14 September 2023.) As stated therein in the abstract:
The human Y chromosome has been notoriously difficult to sequence and assemble
because of its complex repeat structure that includes long palindromes, tandem repeats and segmental duplications. As a result, more than half of the Y chromosome is missing from the GRCh38 reference sequence and it remains the last human chromosome to be finished. Here, the Telomere-to-Telomere (T2T) consortium presents the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference, showing the complete ampliconic structures of gene families TSPY, DAZ and RBMY; 41 additional protein-coding genes, mostly from the TSPY family; and an alternating pattern of human satellite 1 and 3 blocks in the heterochromatic Yq12 region.
It is noted that the subject application was filed on 29 July 2019, and has a priority date of 03 August 2018. It is noted that both of the filing and priority dates predate the determination of the complete human sequence by several years.
Applicant, at page 91, paragraph [0255], teaches:
For example, the nucleic acid target molecules and/or the undesirable nucleic acid species
can comprise DNA molecules, RNA molecules, genomic DNA molecules, cDNA molecules, mRNA molecules, rRNA molecules, mtDNA, siRNA molecules, or any combination thereof. The nucleic acid target molecule can be double-stranded or single-stranded. In some embodiments, the plurality of nucleic acid target molecules can comprise nucleic acids derived from one or more non-nuclear organelles. In some embodiments, the plurality of nucleic acid target molecules can comprise polyA RNA molecules. In some embodiments, the plurality of nucleic acid target molecules comprise at least 100, at least 1,000, at least 10,000, at least 20,000, at least 30,000, at least 40,000, at least 50,000, at least 100,000, at least 1,000,000, or more nucleic acid species. (Emphasis added)
A review of the disclosure fails to find where any Sequence Listing has been provided, much less provide the sequence of the human genome, and lesser still the nucleotide sequence for any virus or bacteria that may be infecting a human cell, e.g., the coronavirus responsible for the COVID-19 pandemic.
In addition to the above, it is also noted that a review of the disclosure fails to find where applicant has identified epitopes of the “nuclear pore complex’ that are unique to the “nuclear pore complex”. Said disclosure has also not been found to provide the requisite “antibody capable of specifically binding a nuclear pore complex”.
As a result of amendment, claim 1 now recites the limitation of:
barcoding copies of a nucleic acid target in the plurality of nuclei using the plurality of barcodes to generate a plurality of barcoded nucleic acid molecules,
wherein each of the plurality of barcodes comprises a molecular label sequence and [[a]] an oligo(dT) target-binding region, and
wherein the molecular label sequences of at least two barcodes of the plurality of barcodes comprise different sequences[.] (Emphasis added)
It stands to reason that any and all mRNA copies will have a polyA sequence, to which the “oligo(dT) target binding region” would hybridize. With mRNA transcripts from different genes all having a polyA sequence, one would not be able to determine how many copies of a specific target are present as it would be binding all polyA sequences in all mRNA transcripts of all genes.
While the barcodes may have different sequences, the barcodes have a common target binding site- an oligo(dT) sequence. The barcodes do not bind selectively to different sequences. Rather, they bind to a common and shared sequence- a polyA sequence. The method does not provide an adequate description of how one would be able to determine how many copies of a specific gene exist when all copies of all transcribed genes bear a polyA sequence.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-2, 8-9, 20, and 28-30 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 10-12 of the response traverses the rejection of claims under 35 USC 112 for not satisfying the written description requirement. At page 11 of the response said representative asserts:
Applicant submits that the claimed methods are focused on a way of determining the copy number of a nucleic acid target in a plurality of cells. The claims are not unpredictable in a way that would trigger a written description rejection.
The above argument has been considered and has not been found persuasive for as noted above, the amended claim no specifies that one is using “an oligo(dT) target-binding region”. It stands to reason that any and all mRNA copies will have a polyA sequence, to which the “oligo(dT) target binding region” would hybridize. With mRNA transcripts from different genes all having a polyA sequence, one would not be able to determine how many copies of a specific target are present as it would be binding all polyA sequences in all mRNA transcripts of all transcribed genes.
While the barcodes may have different sequences, the barcodes have a common target binding site- an oligo(dT) sequence. The barcodes do not bind selectively to different sequences. Rather, they bind to a common and shared sequence- a polyA sequence. The method does not provide an adequate description of how one would be able to determine how many copies of a specific gene exist when all copies of all transcribed genes that bear a polyA sequence.
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 1-2, 8-9, 20, and 28-30 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 1-2, 8-9, 20, and 28-30 are drawn to a “method for determining the copy number of a nucleic acid target in a plurality of cells”, wherein the cells are limited to “human cells”.
The claims do not distinguish between those nucleic acids that do and do not have utility under 35 USC 101 but rather, encompasses any and all manner of nucleic acids that are present in human cells and which has a polyA sequence. Such nucleic acids have been construed as encompassing mRNA, which is recognized as comprising a polyA tail. Attention is directed to page 106, paragraph [0286], of the disclosure wherein applicant asserts:
The nucleus can include one or more target nucleic acid molecules (e.g., messenger RNA (mRNA), microRNA (miRNA), long non-coding RNA (long ncRNA or lncRNA), Piwi-interacting RNA (piRNA)). (Emphasis added)
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.
Applicant, at page 91, paragraph [0255], teaches:
For example, the nucleic acid target molecules and/or the undesirable nucleic acid species
can comprise DNA molecules, RNA molecules, genomic DNA molecules, cDNA molecules, mRNA molecules, rRNA molecules, mtDNA, siRNA molecules, or any combination thereof. The nucleic acid target molecule can be double-stranded or single-stranded. In some embodiments, the plurality of nucleic acid target molecules can comprise nucleic acids derived from one or more non-nuclear organelles. In some embodiments, the plurality of nucleic acid target molecules can comprise polyA RNA molecules. In some embodiments, the plurality of nucleic acid target molecules comprise at least 100, at least 1,000, at least 10,000, at least 20,000, at least 30,000, at least 40,000, at least 50,000, at least 100,000, at least 1,000,000, or more nucleic acid species. (Emphasis added)
It is noted that the “cDNA molecules” are the same as expressed sequence tags, which is a DNA copy of an mRNA molecules. The fact that the target molecules can be “at least 1,000,000, or more nucleic acid species” speaks to the general applicability of the claimed method and how it does not have a specific and substantial utility.
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 1-2, 8-9, 20, and 28-30 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
Applicant’s representative, at apes 12-13 of the response, traverses the rejection of claims under 35 USC 101 for lacking a specific and substantial utility. At page 13 of the response said representative asserts:
Barcoding copies of a nucleic acid target in the plurality of nuclei and estimating the copy number of the nucleic acid target in the plurality of cells using the molecular label sequences of the plurality of barcodes in the sequencing data provides the user with biological insights regarding the cells under observation.
The above cited argument has been considered and has not been found persuasive. As noted above, all mRNA gene transcripts in human cells will have a polyA sequence. While one may be able to determine how many mRNA molecules are present, such does not enable one to determine how many copies of certain gene(s) is / are present. In order to determine how many copies of specific genes will require further research, e.g., sequencing of the individual mRNA molecules and/or using gene-specific probes to hybridize to the coding section of the mRNA molecules. The claims at issue do not recite such limitations. Given such, the rejections are 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..
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Bradley L. Sisson/Primary Examiner, Art Unit 1682