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:
The lettering is not of proper size, uniform density, and well-defined in Figure(s) 1A - 9. See 37 CFR 1.84(p)(1) – (5) and 37 CFR 1.84(l). (“Numbers, letters, and reference characters must measure at least .32 cm (1/8 inch) in height.” They should not cross or mingle with lines.)
The margins are not of proper size in Figure(s) 1A - 14. See 37 CFR 1.84(g).
In Figure(s) 1A - 9 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).
The numbering of the sheets of drawings bearing FIG(s). 1A - 14 is not in compliance with all aspects of 37 CFR 1.84(t).
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.
Response to traversal
Applicant’s representative, at page 5 of the response of 05 February 2026, hereinafter the response, traverses the objections to the drawings. As stated therein:
Regarding Figures 1A-9, the Office alleges that "[t]he lettering is not of proper size, uniform density, and well-defined". Applicant respectfully disagrees and submits that the drawings do comply with 37 CFR 1.84.
Regarding Figures 1A-14, the Office alleges that "[t]he margins are not of proper size". Applicant respectfully disagrees and submits that the drawings do comply with 37 CFR 1.84.
Regarding Figures 1A-9, the Office alleges that "[t]he reference characters, sheet numbers, and view numbers are not all oriented in the same direction so as to avoid having to rotate the sheet". Applicant respectfully disagrees and submits that the drawings do comply with 37 CFR 1.84.
Regarding Figures 1A-14, the Office alleges that "[t]he numbering of the sheets of drawings is not in compliance with all aspects of 37 CFR 1.84(t)". Applicant respectfully disagrees and submits that the drawings do comply with 37 CFR 1.84.
Applicant’s traversals of the objections have been considered and have not been found persuasive. With regard to Figures 1A – 8B, the lowercase lettering in the words “Barcode”, “optional”, “Ligase” and “Splint”, e.g., the letters a, r, c, o, e, a, s, e, a, n, are approximately 1/16 inch in height while the minimum acceptable size is 1/8 inch.
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In the case of Figures 5A – 6B, lines are cutting across the lettering.
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In the case of Fig. 1A to Fig. 9, 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. For convenience 37 CFR 1.84(p)(1) is reproduced below.
(p) Numbers, letters, and reference characters.
(1) Reference characters (numerals are preferred), sheet numbers, and view numbers must be plain and legible, and must not be used in association with brackets or inverted commas, or enclosed within outlines, e.g., encircled. They must be oriented in the same direction as the view so as to avoid having to rotate the sheet. Reference characters should be arranged to follow the profile of the object depicted. (Emphasis added)
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With regard to the numbering of the sheets of drawings bearing FIG(s). 1A – 14 not being in compliance with all aspects of 37 CFR 1.84(t). For convenience 37 CFR 1.84(t) is reproduced below.
(t) Numbering of sheets of drawings. The sheets of drawings should be numbered in consecutive Arabic numerals, starting with 1, within the sight as defined in paragraph (g) of this section. These numbers, if present, must be placed in the middle of the top of the sheet, but not in the margin. The numbers can be placed on the right-hand side if the drawing extends too close to the middle of the top edge of the usable surface. The drawing sheet numbering must be clear and larger than the numbers used as reference characters to avoid confusion. The number of each sheet should be shown by two Arabic numerals placed on either side of an oblique line, with the first being the sheet number and the second being the total number of sheets of drawings, with no other marking. (Emphasis added)
It is noted that the margin where the sheet numbering is to be placed needs to bee 1 inch. The sheet numbering is occurring within that 1 inch margin.
In view of the above analysis and in the absence of convincing evidence to the contrary, the objections are maintained.
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).
Attention is directed to MPEP 2173.04 [R-10.2019]. As stated therein:
Breadth of a claim is not to be equated with indefiniteness. In re Miller, 441 F.2d 689, 169 USPQ 597 (CCPA 1971); In re Gardner, 427 F.2d 786, 788, 166 USPQ 138, 140 (CCPA 1970) ("Breadth is not indefiniteness."). 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)
Claim Rejections - 35 USC § 112, Second Paragraph / (b)
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-01.2024]:
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 [R-01-2024], 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).
Holding and Rationale
Claims 1-30 remain 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 “first probe”, “second probe”, “third probe”, “fist analyte”, “second analyte”, “sample”, “barcode”, and “configured”.
The term “plurality” in claim 1 is a relative term which renders the claim indefinite. The term “plurality” 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 “proximity” in claim 1is a relative term which renders the claim indefinite. The term “proximity” 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 2-30, which depend from claim 1 fail to overcome all of the above-identified issues and are similarly rejected.
Claim 2 is indefinite with respect to what constitutes the metes and bounds of “a tissue sample”.
Claims 3, 8, 9, 11, 12, and 19 are indefinite with respect to what constitutes the metes and bounds of “a nucleic acid”.
Claim 4 is indefinite with respect to what constitutes the metes and bounds of “a ribonucleic acid”.
Claims 6, 7, 13 and 14 are indefinite with respect to what constitutes the metes and bounds of “a polypeptide”.
Claim 15 is indefinite with respect to what constitutes the metes and bounds of antibody and antibody fragment. In support of this position attention to US 6,300,093 B1 (Kindsvogel et al.), which teaches at column 22, last paragraph:
Antibodies of the present invention may be produced by immunizing an animal, a wide variety of warm-blooded animals such as horses, cows, goats, sheep, dogs, chickens, rabbits, mice, and rats can be used, with a recombinant or synthetic islet cell antigen polypeptide or a selected portion thereof (e.g., a peptide).
Attention is also directed to US 2003/0092624 A1 (Wang et al.). As disclosed at paragraph [0194]:
[0194] According to yet an additional aspect of the present invention there is provided an antibody, either polyclonal or monoclonal antibody, recognizing at least one epitope of the polypeptide described herein. The present invention can utilize serum immunoglobulins, polyclonal antibodies or fragments thereof, (i.e., immunoreactive derivative of an antibody), or monoclonal antibodies or fragments thereof. Monoclonal antibodies or purified fragments of the monoclonal antibodies having at least a portion of an antigen binding region, including, such as, Fv, F(ab1)2, Fab fragments (Harlow and Lane, 1988 Antibody, Cold Spring Harbor), single chain antibodies (U.S. Pat. No. 4,946,778), chimeric or humanized antibodies and complementarily determining regions (CDR)… Antibodies of the IgG class are made up of four polypeptide chains linked together by disulfide bonds. The four chains of intact IgG molecules are two identical heavy chains referred to as H-chains and two identical light chains referred to as L-chains. Additional classes includes IgD, IgE, IgA, IgM and related proteins. (Emphasis added)
Attention is also directed to US 2013/0338038 A1 (DuBridge et al.), which teaches the following at paragraph [0061]:
[0061] Examples of suitable sources for immunoglobulin genes include, but are not limited to, humans, primates, rodents (e.g., rat, mouse, hamster, guinea pig, etc.), non-rodents such as sheep, donkey, goat, horse, cow, pig, chicken, llama, camel, dog, cat, rabbit, fish, and birds. In addition to immunoglobulins obtained from various organisms, variant forms of known antibodies can be used, including humanized, chimeric, and monoclonal antibodies. Further, the immunoglobulin molecules or antibodies of the invention can be of any type (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or subclass of immunoglobulin molecule. (Emphasis added)
The term “plurality” in claim 20 is a relative term which renders the claim indefinite. The term “plurality” 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 20 and 21 are indefinite with respect to what constitutes the metes and bounds of a “detection probe”.
Claim 20 is indefinite with respect to what constitutes the metes and bounds of “an anchor probe”.
Claim 23 is indefinite with respect to what constitutes the metes and bounds of “a fluorescent molecule”.
Claim 24 is indefinite with respect to what constitutes the metes and bounds of “imaging”, e.g., type(s) of image files and pixel density.
Claim 25 is indefinite with respect to what constitutes the metes and bounds of “using a confocal microscope”.
Claim 26 is indefinite with respect to what constitutes the metes and bounds of “a hydrogel”.
Claim 27 is indefinite with respect to what constitutes the metes and bounds of an “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.
Claim 29 is indefinite with respect to what form(s) of “amplifying” are encompassed by the claim.
Response to traversal
Applicant’s representative, at pages 5-11 of the response, traverses the rejection of claims for not satisfying the requirements of 35 USC 112(b). Said representative repeats the following argument for each of the rejected claims. As is asserted to therein:
The MPEP notes that "[a] decision on whether a claim is indefinite requires a determination of whether those skilled in the art would understand what is claimed when the claim is read in light of the specification." MPEP 2173.02. (Emphasis added). Further, the MPEP notes that "[e]xaminers are cautioned against confusing claim breadth with claim indefiniteness. A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined." Id. (Emphases added). Applicant submits that a skilled artisan would understand the meaning of…
The above argument has been considered and has not been found persuasive towards the withdrawal of the rejection. In support of this position it is noted that the scope of the various terms have not been “clearly defined”. In support of this position attention is directed to paragraph [0215] of the disclosure. As is asserted to therein:
[0215] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the invention be limited by the specific examples provided within the specification. While the invention has been described with reference to the aforementioned specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. Furthermore, it shall be understood that all aspects of the invention are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is therefore contemplated that the invention shall also cover any such alternatives, modifications, variations or equivalents. (Emphasis added)
As evidenced above, the disclosure comprises assertions that the invention is not limited to that which has been disclosed, but encompasses any number of “variations, changes and substitutions”. Given such, it is less than clear as to just what does constitute the metes and bounds of all aspects of the claimed invention. In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-30 remain 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, Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Standard for Written Description.
Attention is directed to MPEP 2163.02 Standard for Determining Compliance With the Written Description Requirement [R-07-2022]:
An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. (Emphasis added)
Attention is also set directed to MPEP 2161.01 I [R-07-2022], wherein is stated:
For instance, generic claim language in the original disclosure does not satisfy the written description requirement if it fails to support the scope of the genus claimed. Ariad, 598 F.3d at 1349-50, 94 USPQ2d at 1171 ("[A]n adequate written description of a claimed genus requires more than a generic statement of an invention’s boundaries.") (citing Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1405-06); Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002) (holding that generic claim language appearing in ipsis verbis in the original specification did not satisfy the written description requirement because it failed to support the scope of the genus claimed); Fiers v. Revel, 984 F.2d 1164, 1170, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (rejecting the argument that "only similar language in the specification or original claims is necessary to satisfy the written description requirement").
As set forth in Fiers v. Revel 25 USPQ2d 1601, 1604-5 (CAFC, January 1993):
We thus determined that, irrespective of the complexity or simplicity of the method of isolation employed, conception of a DNA, like conception of any chemical substance, requires a definition of that substance other than by its functional utility.
Fiers' attempt to distinguish Amgen therefore is incorrect. We also reject Fiers' argument that the existence of a workable method for preparing a DNA establishes conception of that material. (Emphasis added)
Conception of a substance claimed per se without reference to a process requires conception of its structure, name, formula, or definitive chemical or physical properties...
The difficulty that would arise if we were to hold that a conception occurs when one has only an idea of a compound, defining it by its hoped-for function, is that would-be inventors would file patent applications before they had made their inventions and before they could describe them. That is not consistent with the statute or the policy behind the statute, which is to promote disclosure of inventions.
As set forth in the en banc decision in Ariad Pharmaceuticals Inc. v. Eli Lilly and Company, 94 USPQ2d 1161 (Fed. Cir. 2010) at 1171:
We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus. Id. at 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 [25 USPQ2d 1601] (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001)). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
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In Fiers, we rejected the argument that “only similar language in the specification or original claim is necessary to satisfy the written description requirement.” 984 F.2d at 1170 (emphasis added). Rather, we held that original claim language to “a DNA coding for interferon activity” failed to provide an adequate written description as it amounted to no more than a “wish” or “plan” for obtaining the claimed DNA rather than a description of the DNA itself. Id. at 1170-71. That Fiers applied § 112, first paragraph, during an interference is irrelevant for, as we stated above, the statute contains no basis for ignoring the description requirement outside of this context. And again in Enzo we held that generic claim language appearing in ipsis verbis in the original specification does not satisfy the written description requirement if it fails to support the scope of the genus claimed. 323 F.3d at 968. We concluded that “[a] claim does not become more descriptive by its repetition, or its longevity.” Id. at 969.
***
The written description requirement also ensures that when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function—a problem that is particularly acute in the biological arts.
Attention is also directed to MPEP 2163 Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, “Written Description” Requirement [R-01-2024], at part II ii):
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ( "[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).") (Emphasis added)
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 1-30 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.
Claims 1-6 and 14 are deemed to be representative and, for convenience, are reproduced below.
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Applicant, at page 18, paragraph [0057], asserts:
[0057] Provided herein are methods, compositions and systems for the detecting the proximity of analytes within a sample using probes. The detection methods described herein can detect the relationship between one or more analyte within a sample with high accuracy, high specificity, high sensitivity, or a combination thereof. A variety of types of analytes can be detected using these methods. Additionally, a variety of probe types can be used to detect one or more analyte as part of the methods described herein. (Emphasis added)
Applicant, at page 63, paragraph [0129], asserts:
[0129] In cases where the second analyte comprises a nucleic acid, the nucleic acid may comprise one or more genetic aberrations. The one or more genetic aberrations of the second analyte may comprise one or more insertions, one or more deletions, one or more copy number variations, one or more single nucleotide polymorphisms, one or more single nucleotide variants, or a combination thereof. The one or more single nucleotide polymorphisms of the second analyte may comprise one or more variants relative to a reference genome. The reference genome may comprise a human reference genome, a mouse reference genome, a synthetic reference genome or a combination thereof. (Emphasis added)
Applicant, at paragraphs [0143] and [0144] (pages 73 and 74), asserts:
[0143] The second probe may comprise an aptamer. The aptamer of the second probe may comprise a nucleic acid. The aptamer of the second probe may comprise a secondary structure, a tertiary structure or a combination thereof. The aptamer may be configured to recognize, bind to, and/or couple to an analyte. For example, the aptamer may comprise a sequence and associated tertiary structure that recognizes and binds to a protein or interest. The analyte recognized by, bound to, and/or coupled to by the aptamer may be the second analyte. The analyte recognized by, bound to, and/or coupled to by the aptamer may comprise a nucleic acid, a polypeptide, or a combination thereof. For example, the analyte may comprise a DNA-binding protein comprising an epitope recognized by the aptamer. The aptamer may comprise RNA, DNA, a polypeptide, xeno nucleic acid (XNA), or a combination thereof. The aptamer may have a molecular weight of at least about 1 kilodaltons (kDa), at least about 2 kDa, at least about 3 kDa, at least about 4 kDa, at least about 5 kDa, at least about 6 kDa, at least about 7 kDa, at least about 8 kDa, at least about 9 kDa, at least about 10 kDa, at least about 11 kDa, at least about 12 kDa, at least about 13 kDa, at least about 14 kDa, at least about 15 kDa, at least about 16 kDa, at least about 17 kDa, at least about 18 kDa, at least about 19 kDa, at least about 20 kDa, at least about 21 kDa, at least about 22 kDa, at least about 23 kDa, at least about 24 kDa, at least about 25 kDa, at least about 26 kDa, at least about 27 kDa, at least about 28 kDa, at least about 29 kDa, at least about 30 kDa, at least about 31 kDa, at least about 32 kDa, at least about 33 kDa, at least about 34 kDa, at least about 35 kDa, at least about 36 kDa, at least about 37 kDa, at least about 38 kDa, at least about 39 kDa, at least about 40 kDa, at least about 41 kDa, at least about 42 kDa, at least about 43 kDa, at least about 44 kDa, at least about 45 kDa, at least about 46 kDa, at least about 47 kDa, at least about 48 kDa, at least about 49 kDa, or at least about 50 kDa. The aptamer may have a molecular weight of at most about 1 kDa, at most about 2 kDa, at most about 3 kDa, at most about 4 kDa, at most about 5 kDa, at most about 6 kDa, at most about 7 kDa, at most about 8 kDa, at most about 9 kDa, at most about 10 kDa, at most about 11 kDa, at most about 12 kDa, at most about 13 kDa, at most about 14 kDa, at most about 15 kDa, at most about 16 kDa, at most about 17 kDa, at most about 18 kDa, at most about 19 kDa, at most about 20 kDa, at most about 21 kDa, at most about 22 kDa, at most about 23 kDa, at most about 24 kDa, at most about 25 kDa, at most about 26 kDa, at most about 27 kDa, at most about 28 kDa, at most about 29 kDa, at most about 30 kDa, at most about 31 kDa, at most about 32 kDa, at most about 33 kDa, at most about 34 kDa, at most about 35 kDa, at most about 36 kDa, at most about 37 kDa, at most about 38 kDa, at most about 39 kDa, at most about 40 kDa, at most about 41 kDa, at most about 42 kDa, at most about 43 kDa, at most about 44 kDa, at most about 45 kDa, at most about 46 kDa, at most about 47 kDa, at most about 48 kDa, at most about 49 kDa, or at most about 50 kDa. The aptamer may have a molecular weight of about 1 to about 50 kDa, about 2 to about 49 kDa, about 3 to about 48 kDa, about 4 to about 47 kDa, about 5 to about 46 kDa, about 6 to about 45 kDa, about 7 to about 44 kDa, about 8 to about 43 kDa, about 9 to about 42 kDa, about 10 to about 41 kDa, about 11 to about 40 kDa, about 12 to about 39 kDa, about 13 to about 38 kDa, about 14 to about 37 kDa, about 15 to about 36 kDa, about 16 to about 35 kDa, about 17 to about 34 kDa, about 18 to about 33 kDa, about 19 to about 32 kDa, about 20 to about 31 kDa, about 21 to about 30 kDa, about 22 to about 29 kDa, about 23 to about 28 kDa, or about 24 to about 27 kDa, about 25 to about 26 kDa.
[0144] The second probe may comprise a polypeptide. The polypeptide of the second probe may comprise a protein, a peptide or a combination thereof. The protein of the polypeptide of the second probe comprises a be a protein-binding protein, a DNA-binding protein, or a combination thereof. The protein of the polypeptide of the second probe may be a nucleic acid binding protein. The protein may comprise an antibody, antibody fragment, affimer, nanobody, or a combination thereof. The antibody or antibody fragment of the second probe may comprise a variety of isotypes including but not limited to IgG, IgM, IgA, IgD, IgE, or a combination thereof. The antibody or antibody fragment of the second probe may comprise an fc domain that recognizes an analyte (e.g. the second analyte ). The second probe may comprise one or more antibodies or antibody fragments. In some cases, the second probe may comprise an antibody that recognizes, binds to, and/or couples to the second analyte and an antibody that recognizes, binds to, and/or couples to the antibody that that recognizes, binds to, and/or couples to the second analyte. One or more of the antibodies of the second probe may comprise one or more modifications. The one or more modifications of the one or more antibodies of the second probe may comprise a nucleic acid modification conjugated to one or more of the antibodies or antibody fragments of the second probe either directly or indirectly. The nucleic acid modification of the second probe may comprise a binding site (e.g. the fourth binding site of the second probe). The binding site of the nucleic acid modification of the second probe may serve as a primer to initiate amplification. The binding site of the nucleic acid modification of the second probe may serve as a binding site for one or more portions of the first probe and/or third probe, and upon binding of the one or more portions of the first probe, may initiate ligation of one end of the first probe to another end of the first probe and/or another end of the third probe.
A review of the disclosure fails to find where applicant has provided a Sequence Listing
that discloses the nucleotide sequence for any DNA or RNA molecule, be it a probe or target. Such sequences are deemed to constituted essential material1. Likewise, the disclosure has not been found to provide the animo acid sequence for any protein target, much less any epitope on or in said protein/polypeptide. Additionally, the disclosure has not been found to provide the amino acid sequence for any part of any antibody. Such nondisclosure by applicant of such essential materials of the claimed method has not been found to reasonably suggest that applicant, as of the filing date sought, was in possession of the invention.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-30 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 11-12 of the response said representative traverses the rejection of clams under 35 USC 112(a) for not satisfying the written description requirement. At page 12 of the response said representative asserts:
As an initial matter, Applicant submits that the disclosure of a particular nucleotide or amino acid sequence is not necessary for reasonably conveying to the skilled artisan that the inventor had possession of the claimed invention. In addition, Applicant submits that the Office has not provided a reasoning why these particular features are needed to prove that the Applicant was in possession of the invention at the time of the filing date sought. The MPEP makes clear that the scope of what is needed to determine that the Applicant was in possession of the invention as of the filing date is not a myopic exercise requiring a specific type of evidence regardless of the scope and/or type of invention. Applicant submits that the Office is incorrectly applying the standard for determining the written description requirement by requiring a particular type of evidence, in this case a sequence listing of specific nucleic acids and/or amino acids, rather than considering the scope of the invention. Applicant submits that they were in possession of the invention as of the filing date of the priority document and that claims 1-30 do comply with the written description requirement.
Accordingly, Applicant respectfully requests that the § 112(a) rejection of claims 1-30 be withdrawn.
The above argument has been considered and has not been found persuasive. While the claims are drawn to “a method” and not to a product, e.g., target proteins, target nucleic acids, nucleic acid aptamers, antibodies and fragments of same and of any type, applicant still needs to provide an adequate written description of these components of the claimed invention, wherein said disclosure is representative of the very broad breadth of scope of the claimed invention. In support of this position attention is again directed to Rochester:
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 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.
64. 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)
A review of the disclosure fails to find where applicant has provided any Sequence Listing of such essential sequences (nucleic acid and amino acid), nor provided any antibody or antibody fragment, wherein the antibodies are produced by any of the art recognized animals. The disclosure has not been found to provide a description of the epitopes on the genus of molecules to which the antibodies and aptamers are to bind. Such nondisclosure of targets and probes has not been found to reasonably suggest that applicant, as of the effective filing date, was in possession of this very broad genus of target molecules and probes, be they nucleic acid or not.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-30 remain 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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting over claims 1-30 of copending Application No. 19/236720. This is a provisional double patenting rejection because the patentably indistinct claims have not in fact been patented.
The subject matter claimed in the instant application is fully disclosed in the referenced copending application and would be covered by any patent granted on that copending application since the referenced copending application and the instant application are claiming common subject matter, as follows: The claims of the instant application are drawn to a method that results in the detection of the complement of a barcode or a derivative thereof using a plurality of detection probes while the claims of the ‘720 application are drawn to “a method of detecting analytes in a sample” using a plurality of detection probes. In both applications, the probes can be nucleic acid as well as an antibody or an antibody fragment.
Furthermore, there is no apparent reason why applicant would be prevented from presenting claims corresponding to those of the instant application in the other copending application. See In re Schneller, 397 F.2d 350, 158 USPQ 210 (CCPA 1968). See also MPEP § 804.
Response to traversal
At page 12, bridging to page 13 of the response said representative traverses the nonstatutory double patenting rejection of claims in view of the 19/236720 application. As is asserted to therein:
Applicant submits that the instant claims are patentably distinct over claims 1-30 of the '720 Application. For example, none of claims 1-30 of the '720 Application are directed to "a third probe wherein said third probe comprises: (i) a sixth binding site configured to couple to said second probe; (ii) a seventh binding site configured to couple to said first analyte; (iii) a third end, wherein said third end is adjacent to said first end; and (iv) a fourth end, wherein said fourth end is adjacent to said second end," as recited in claim 1 of the instant Application. Applicant submits that the pending claims are patentably distinct over claims 1-30 of the '720 Application. Applicant respectfully requests that the double patenting rejection of claims 1-30 be withdrawn.
For convenience, claim 1 of the ‘720 application is reproduced below.
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As an initial matter it is noted that the rejection is not one of statutory double patenting where the claims are identical. Rather, the rejection is a nonstatutory double patenting rejection. As evidenced above, claim 1 of the ‘720 application comprises first and second probes just lie the ‘7322 application. Likewise, the aspect of using two probes and not three, where the two probes allow “determining a proximity of said first and second analyte” is deemed to constitute an obvious design choice.
In view of the above analysis and in the absence of convincing evidence to the contrary, the rejection is maintained.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Standard for Obviousness.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Attention is directed to In re Jung, 98 USPQ2d 1174, 1178 (Fed. Cir. 2011) wherein is stated:
There has never been a requirement for an examiner to make an on-the-record claim construction of every term in every rejected claim and to explain every possible difference between the prior art and the claimed invention in order to make out a prima facie rejection. This court declines to create such a burdensome and unnecessary requirement. “[Section 132] does not mandate that in order to establish prima facie anticipation, the PTO must explicitly preempt every possible response to a section 102 rejection. Section 132 merely ensures that an applicant at least be informed of the broad statutory basis for the rejection of his claims, so that he may determine what the issues are on which he can or should produce evidence.” Chester, 906 F.2d at 1578 (internal citation omitted). As discussed above, all that is required of the office to meet its prima facie burden of production is to set forth the statutory basis of the rejection and the reference or references relied upon in a sufficiently articulate and informative manner as to meet the notice requirement of § 132. As the statute itself instructs, the examiner must “notify the applicant,” “stating the reasons for such rejection,” “together with such information and references as may be useful in judging the propriety of continuing prosecution of his application.” 35 U.S.C. § 132.
Attention is directed to the decision in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007):
When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill in the art has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
It is further noted that prior art is not limited to the four corners of the documentary prior art being applied. Prior art includes both the specialized understanding of one of ordinary skill in the art, and the common understanding of the layman. It includes “background knowledge possessed by a person having ordinary skill in the art. . . [A] court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1396.
Suggestion, teaching or motivation does not have to be explicit and “may be found in any number of sources, including common knowledge, the prior art as a whole or the nature of the problem itself’” Pfizer, Inc. v. Apotex, Inc. 480 F.3d 1348, 82 USPQ2d 1321 (Fed. Cir. 2007) citing Dystar Textilfarben GMBH v. C. H. Patrick Co., 464 F.3d 1356 (Fed. Cir. 2006).
Holding and Rationale
Claims 1-30 are rejected under 35 U.S.C. 103 as being unpatentable over US 2023/0126825 A1 (Nagendran et al.).
Nagendran et al., teach:
[0007] In some instances, the analyte derived molecule is a ligation product. In some instances, the method further includes, prior to step (b): contacting a plurality of first probes and second probes to the biological sample on the array, wherein the plurality of first probes and second probes target a plurality of nucleic acids in the biological sample, wherein a first probe and a second probe of the plurality comprise sequences that are substantially complementary to the analyte, wherein the analyte is a target nucleic acid, and wherein the second probe comprises a capture probe capture domain sequence that is complementary to all or a portion of the capture domain; hybridizing the first probe and the second probe to the target nucleic acid; generating a ligation product by ligating the first probe and the second probe; and releasing the ligation product from the target nucleic acid. (Emphasis added)
[0008] In some instances, the first probe and the second probe are substantially complementary to adjacent sequences of the target nucleic acid. In some instances, the first probe and the second probe hybridize to sequences that are not adjacent to each other on the target nucleic acid, and wherein the first probe is extended with a DNA polymerase, thereby (i) filling in a gap between the first probe and the second probe and (ii) generating an extended first probe. In some instances, the first probe further comprises a primer sequence. In some instances, the first probe and/or the second probe is a DNA probe. In some instances, the releasing the ligation product from the target nucleic acid comprises contacting the biological sample with an endoribonuclease, optionally wherein the endoribonuclease is an RNase H enzyme. (Emphasis added)
[0009] In some instances, the analyte derived molecule is an analyte capture agent. In some instances, the methods further include, prior to step (b): contacting the biological sample with a plurality of analyte capture agents, wherein the analyte capture agent comprises an analyte binding moiety and an oligonucleotide comprising an analyte binding moiety barcode and an analyte capture sequence, wherein the analyte capture sequence comprises a sequence complementary to the capture domain; and binding the analyte binding moiety of the analyte capture agent to the analyte, wherein the analyte is a protein. In some instances, step (b) comprises hybridizing the analyte capture sequence to the capture domain. (Emphasis added)
[0031] In some embodiments, determining the mislocalization of the analyte includes measuring the signal intensity of the plurality of detection probes and comparing the signal intensity to a first image of the biological sample. In some embodiments, signal intensity in the image of the biological sample includes a single cell or cell type that expresses a biomarker that is detected when the biological sample is stained.
[0039] In some embodiments, the biological sample includes a tissue section. In some embodiments, the tissue section is about 2.5 μm to about 20 μm in thickness.
[0041] In some embodiments, the analyte is RNA. In some embodiments, the RNA is mRNA. In some embodiments, the analyte is a protein. In some embodiments, the protein is a cell surface marker. In some embodiments, the protein is an immune cell receptor. (Emphasis added)
[0043] In some embodiments, the method also includes determining abundance and/or location of an analyte in the second biological sample, wherein the determining includes: (a) contacting a spatial array with the second biological sample, wherein the spatial array includes a plurality of spatial capture probes, wherein a spatial capture probe of the plurality of spatial capture probes includes a capture domain and a spatial barcode; (b) hybridizing the analyte to the spatial capture probe; and (c) determining (i) all or a part of the sequence of the analyte, or a complement thereof, and (ii) the sequence of the spatial barcode… (Emphasis added)
[0071] Spatial analysis methodologies and compositions described herein can provide a vast amount of analyte and/or expression data for a variety of analytes within a biological sample at high spatial resolution, while retaining native spatial context. Spatial analysis methods and compositions can include, e.g., the use of a capture probe including a spatial barcode (e.g., a nucleic acid sequence that provides information as to the location or position of an analyte within a cell or a tissue sample (e.g., mammalian cell or a mammalian tissue sample) and a capture domain that is capable of binding to an analyte (e.g., a protein and/or a nucleic acid) produced by and/or present in a cell. Spatial analysis methods and compositions can also include the use of a capture probe having a capture domain that captures an intermediate agent for indirect detection of an analyte. For example, the intermediate agent can include a nucleic acid sequence (e.g., a barcode) associated with the intermediate agent. Detection of the intermediate agent is therefore indicative of the analyte in the cell or tissue sample. (Emphasis added)
[0073] Some general terminology that may be used in this disclosure can be found in Section (I)(b) of WO 2020/176788 and/or U.S. Patent Application Publication No. 2020/0277663. Typically, a “barcode” is a label, or identifier, that conveys or is capable of conveying information (e.g., information about an analyte in a sample, a bead, and/or a capture probe). A barcode can be part of an analyte, or independent of an analyte. A barcode can be attached to an analyte. A particular barcode can be unique relative to other barcodes. For the purpose of this disclosure, an “analyte” can include any biological substance, structure, moiety, or component to be analyzed. The term “target” can similarly refer to an analyte of interest. (Emphasis added)
[0074] Analytes can be broadly classified into one of two groups: nucleic acid analytes, and non-nucleic acid analytes. Examples of non-nucleic acid analytes include, but are not limited to, lipids, carbohydrates, peptides, proteins, glycoproteins (N-linked or O-linked), lipoproteins, phosphoproteins, specific phosphorylated or acetylated variants of proteins, amidation variants of proteins, hydroxylation variants of proteins, methylation variants of proteins, ubiquitylation variants of proteins, sulfation variants of proteins, viral proteins (e.g., viral capsid, viral envelope, viral coat, viral accessory, viral glycoproteins, viral spike, etc.), extracellular and intracellular proteins, antibodies, and antigen binding fragments. In some embodiments, the analyte(s) can be localized to subcellular location(s), including, for example, organelles, e.g., mitochondria, Golgi apparatus, endoplasmic reticulum, chloroplasts, endocytic vesicles, exocytic vesicles, vacuoles, lysosomes, etc. In some embodiments, analyte(s) can be peptides or proteins, including without limitation antibodies and enzymes. Additional examples of analytes can be found in Section (I)(c) of WO 2020/176788 and/or U.S. Patent Application Publication No. 2020/0277663. In some embodiments, an analyte can be detected indirectly, such as through detection of an intermediate agent, for example, an analyte derived molecule such as a connected probe (e.g., a ligation product) or an analyte capture agent (e.g., an oligonucleotide-conjugated antibody), such as those described herein. (Emphasis added)
[0075] A “biological sample” is typically obtained from the subject for analysis using any of a variety of techniques including, but not limited to, biopsy, surgery, and laser capture microscopy (LCM), and generally includes cells and/or other biological material from the subject. In some embodiments, a biological sample can be a tissue section. In some embodiments, a biological sample can be a fixed and/or stained biological sample (e.g., a fixed and/or stained tissue section). Non-limiting examples of stains include histological stains (e.g., hematoxylin and/or eosin) and immunological stains (e.g., fluorescent stains).
[0078] A “capture probe” refers to any molecule capable of capturing (directly or indirectly) and/or labelling an analyte (e.g., an analyte of interest) in a biological sample. In some embodiments, the capture probe is a nucleic acid or a polypeptide. In some embodiments, the capture probe includes a barcode (e.g., a spatial barcode and/or a unique molecular identifier (UMI)) and a capture domain). In some embodiments, a capture probe can include a cleavage domain and/or a functional domain (e.g., a primer-binding site, such as for amplification, or a flow cell attachment sequence, such as for next-generation sequencing (NGS)). (Emphasis added)
[0085] In some embodiments, more than one analyte type (e.g., nucleic acids and proteins) from a biological sample can be detected (e.g., simultaneously or sequentially) using any appropriate multiplexing technique, such as those described in Section (IV) of WO 2020/176788 and/or U.S. Patent Application Publication No. 2020/0277663. (Emphasis added)
[0086] In some embodiments, detection of one or more analytes (e.g., protein analytes) can be performed using one or more analyte capture agents. As used herein, an “analyte capture agent” refers to an agent that interacts with an analyte (e.g., an analyte in a biological sample) and with a capture probe (e.g., a capture probe attached to a substrate or a feature) to identify the analyte. In some embodiments, the analyte capture agent includes: (i) an analyte binding moiety (e.g., that binds to an analyte), for example, an antibody or antigen-binding fragment thereof; (ii) analyte binding moiety barcode; and (iii) a capture handle sequence. As used herein, the term “analyte binding moiety barcode” refers to a barcode that is associated with or otherwise identifies the analyte binding moiety. As used herein, the term “analyte capture sequence” or “capture handle sequence” refers to a region or moiety configured to hybridize to, bind to, couple to, or otherwise interact with a capture domain of a capture probe. In some embodiments, a capture handle sequence is complementary to a capture domain of a capture probe. In some cases, an analyte binding moiety barcode (or portion thereof) may be able to be removed (e.g., cleaved) from the analyte capture agent. (Emphasis added)
[0115] Thus, disclosed herein are methods of determining analyte mislocalization within a biological sample, the method including: (a) obtaining a first image of the biological sample; (b) hybridizing the analyte or analyte derived molecule to a capture probe on an array, wherein the array includes a plurality of capture probes, wherein a capture probe of the plurality of capture probe includes a capture domain; (c) optionally extending the capture probe using the analyte as a template, thereby generating an extended capture probe; (d) hybridizing a padlock probe or a snail probe to the analyte derived molecule or extended capture probe; (e) circularizing the padlock probe or the snail probe; (f) amplifying the padlock probe or the snail probe, thereby generating an amplified circularized padlock probe or an amplified circularized snail probe; (g) hybridizing a plurality of detection probes to the amplified circularized padlock probe or the amplified circularized snail probe, wherein a detection probe from the plurality of detection probes comprises: a sequence that is substantially complementary to a sequence of the padlock probe or the snail probe, or a complement thereof, and a detectable label; (h) obtaining a second image of the biological sample and detecting a signal from the plurality of detection probes in the second image; and (i) determining mislocalization of the analyte within the biological sample by comparing the first image of the biological sample to the second image of the biological sample. (Emphasis added)
[0125] In other embodiments, probes can be designed so that one of the probes of a pair is a probe that hybridizes to a specific sequence. Then, the other probe can be designed to detect a mutation of interest. (Emphasis added)
[0130] In some embodiments, proteins in a biological sample can be detected using analyte capture agents, as described herein. In some embodiments, the analyte capture agents are contacted with the biological sample before the biological sample is contacted with an array. In some embodiments, the analyte capture agents are contacted with the biological sample after the biological sample is contacted with the array. In some embodiments, an analyte binding moiety of the analyte capture agent interacts (e.g., binds) with an analyte (e.g., protein) in a biological sample. In some embodiments, the analyte binding moiety is an antibody, aptamer or antigen-binding fragment. (Emphasis added)
[0134] In some embodiments, analyte capture agents are capable of binding to analytes present inside a cell. In some embodiments, analyte capture agents are capable of binding to cell surface analytes that can include, without limitation, a receptor, an antigen, a surface protein, a transmembrane protein, a cluster of differentiation protein, a protein channel, a protein pump, a carrier protein, a phospholipid, a glycoprotein, a glycolipid, a cell-cell interaction protein complex, an antigen-presenting complex, a major histocompatibility complex, an engineered T-cell receptor, a T-cell receptor, a B-cell receptor, a chimeric antigen receptor, an extracellular matrix protein, a posttranslational modification (e.g., phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation or lipidation) state of a cell surface protein, a gap junction, and an adherens junction. In some embodiments, the analyte capture agents are capable of binding to cell surface analytes that are post-translationally modified.
[0160] In some embodiments, the detecting step includes contacting the amplified circularized padlock probe or snail probe with a plurality of detection probes. In some embodiments, a detection probe of the plurality of detection probes includes a sequence that is substantially complementary to a sequence of the padlock probe or snail probe, circularized padlock probe or snail probe, or amplified circularized padlock probe or snail probe and a detectable label. For example, the detection probe of the plurality of detection probes can include a sequence that is substantially complementary to a sequence of amplified circularized padlock probe or snail probe and a detectable label. (Emphasis added)
[0162] In some embodiments, a detection probe of the plurality of detection probes includes a nucleotide sequence that is different from other detection probes, thereby enabling detection of signals from two or more detection probe sequences (e.g., two or more different amplified circularized padlock probe or snail probe). (Emphasis added)
[0166] In some embodiments, the method includes repeating the detecting step with a second plurality of detection probes. In such cases, the method includes removing the detection probes from the first detecting step (e.g., via enzymatic digestion) and contacting the amplified circularized padlock probe or snail probe with a second plurality of detection probes. A detection probe of the second plurality of detection probes includes a sequence that is substantially complementary to a sequence of the padlock probe or snail probe and that is non-overlapping, partially overlapping, or completely overlapping with the sequence to which a detection probe from the first plurality of detection probes is substantially complementary.
[0172] In some embodiments, the methods are applied to analyte, or analyte derived molecules (e.g., an mRNA molecule, a gDNA molecule, a product of reverse transcription (e.g., an extended capture probe), and an analyte binding moiety barcode (e.g., a binding moiety barcode that identifies that analyte binding moiety (e.g., an antibody))). In some embodiments, the analyte or analyte derived molecules comprise RNA and/or DNA. In some embodiments, the analyte or analyte derived molecules comprise one or more proteins. (Emphasis added)
[0174] In some instances, the biological sample is a section of a tissue (e.g., a 10 μm section). (Emphasis added)
In view of the above presentation, Nagendran et al., is deemed to at least render obvious, if not anticipate, the claimed method which can be both nucleic acids and proteins, using a plurality of probes, which can be nucleic acid probes and/or antibodies or fragments of same as well as binding sites that can allow for the binding or “coupling” of probes of the plurality of probes.
As seen in paragraph [0162], Nagendran et al., each using “two or more detection probes”. Such is deemed to render obvious the use of a “third probe”.
In view of the above showing of the prior art, claims 1-30 remain rejected under 35 U.S.C. 103 as being unpatentable over US 2023/0126825 A1 (Nagendran et al.).
Response to traversal
Applicant’s representative, at page 13 of the response, traverses the rejection of claims under 35 USC 103(a). As asserted to therein, argument is presented that Nagendran et al., does not reach using a third probe. This argument has been considered and has not been found for as seen in paragraph [0162], Nagendran et al., teach of using “two or more detection probes”. The aspect of using more than two is deemed to render obvious the use of three such probes.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1-30 remain rejected under 35 U.S.C. 103 as being unpatentable over US 2023/0126825 A1 (Nagendran et al.).
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM.
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682
1 Attention is directed to 37 CFR 1.57(d), which sates in part:
(d) "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. "Essential material" is material that is necessary to:
(1) Provide a written description of the claimed 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 set forth the best mode contemplated by the inventor of carrying out the invention as required by 35 U.S.C. 112(a);
(2) Describe the claimed invention in terms that particularly point out and distinctly claim the invention as required by 35 U.S.C. 112(b); or
(3) Describe the structure, material, or acts that correspond to a claimed means or step for performing a specified function as required by 35 U.S.C. 112(f). (Emphasis added)
(e) Other material ("Nonessential material") may be incorporated by reference to U.S. patents, U.S. patent application publications, foreign patents, foreign published applications, prior and concurrently filed commonly owned U.S. applications, or non-patent publications. An incorporation by reference by hyperlink or other form of browser executable code is not permitted.