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
Applicant's election with traverse in the reply filed on 12/22/2025 is acknowledged:
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The traversal is on the ground(s) that the elected and non-elected claims require substantially overlapping proof for examination. This is not found persuasive because Applicant has not indicated that the Groups of invention are not patentably distinct.
The requirement is still deemed proper and is therefore made FINAL.
Based on the election, claims 1-21 and 39 cover the elected invention and are treated in the merits, below. Claims 22-38 are withdrawn from consideration as exclusively covering a non-elected invention.
Specification
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Applicant is required to review the Application for any deficiencies with the sequence requirements set forth, above.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-21 and 39 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.
The rejected claims cover (i) a first oligonucleotide conjugate comprising a first single strand oligonucleotide conjugated to a biomolecule, wherein the first single strand oligonucleotide comprises a first nucleotide sequence; and/or (ii) a second oligonucleotide conjugate comprising a second single strand oligonucleotide conjugated to an agent, wherein the second single strand oligonucleotide comprises a second nucleotide sequence being complementary to the first nucleotide sequence; wherein the first and second oligonucleotide conjugates form a double-strand oligonucleotide conjugate which comprises a hybridized oligonucleotide bridge region between the first nucleotide sequence and the second nucleotide sequence, whereby the biomolecule and the agent are linked together in the double-strand oligonucleotide conjugate.
To satisfy the written-description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. Vas-Cath, 935 F.3d at 1563; see also Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention”); In re Gosteli, 872 F.2d 1008, 1012 (Fed. Cir. 1989) (“the description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed”).
With regard to the recited genus of biomolecules and agents, the following applies:
Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 94 USPQ2d 1161 (Fed. Cir. 2010) states that “...a generic claim may define the boundaries of a vast genus of chemical compounds...the question may still remain whether the specification, including the original claim language, demonstrates that the applicant invented species sufficient to support a claim to a genus”. See page 1171.
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, reduction to drawings, 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 applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
See also Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) (a “laundry list” disclosure of every possible moiety does not constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species.
Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) states that “it is well established in our law that conception of a chemical compound requires that the inventor be able to define it so as to distinguish it from other materials, and to describe how to obtain it”.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or structural features common to the members of the genus, which features constitute a substantial portion of the genus, so that one of skill in the art can “visualize or recognize” the members of the genus (Emphasis added). Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997).
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B(i), the court states, "An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention."
Courts have stated that “[i]n claims involving [non-genetic] chemical materials, generic formulae 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 description of the claimed genus.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). (emphasis added).
There is no such specificity here, nor could one skilled in the art identify biomolecules and agents encompassed by the claims. To the contrary, the specification states that the claimed compounds are derived from the recited substituents.
Here, Applicant desires patent protection for oligonucleotide conjugates comprising biomolecules and agents. However, in view of the above, the specification does not provide adequate written description of the claimed genus of biomolecules and agents. Specifically, Applicant fails to disclose any other biomolecules and agents, besides those covered by the specification, and in relation to the above, these disclosed species or subgenre do not represent the substantial variety covered by the genus of biomolecules and agents.
With regard to the functional definition of biomolecule or agents, the specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed (see Vas-Cath at page 1116) because the specification contains almost no information by which a person of ordinary skill in the art would understand that the inventors possessed the all of the recited compounds. At best, it simply indicates that one should test an inordinate number of compounds and molecules to see if the compounds can perform the required function. In this connection, the specification contains no structural or specific functional characteristics of those compounds which are intended to be biomolecules ad agents, besides those compounds and molecules instantly disclosed, see In re ’318 Patent Infringement Litigation, 583 F.3d 1317, 1327 (Fed. Cir. 2009) (“[A]t the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient.”).
The Examiner acknowledges that a working example or exemplified embodiment is not necessarily a requirement for description. However, where a generic claim term is present in a claim, as in the present application, and defined only by functional characteristics, the specification must convey enough information, e.g., via sufficient representative examples, to indicate invention of species sufficient to constitute the genus. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 967 2 (Fed. Cir. 2002). The written description requirement “requires a description of an invention, not an indication of a result that one might achieve if one made that invention.” Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997); see also Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1350 (Fed. Cir. 2013) (“A patent...‘is not a reward for the search, but compensation for its successful conclusion.’ ... For that reason, the written description requirement prohibits a patentee from ‘leaving it to the ... industry to complete an unfinished invention.’” (citations omitted)).
Accordingly, the specification lacks adequate written description for the recited biomolecules and agents.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 7-9, 13-21 and 39 are rejected under 35 U.S.C. 102(a)(1) or 102(a)(2) as being anticipated by WO 2017190020 (WO 020).
The claims recite (i) a first oligonucleotide conjugate and/or (ii) a second oligonucleotide conjugate. The elected species, see above, requires both the first and second oligonucleotide conjugates and WO 020 is applied in that manner.
Regarding claims 1, 3, 8, 17, 18 and 39, WO 020 discloses an oligonucleotide conjugate ([o]ligonucleotide conjugates, Para. [0007]), comprising (i) a first oligonucleotide conjugate comprising a first single strand oligonucleotide conjugated to a biomolecule (the oligonucleotide component comprises a first universal sequence, Para. [0009]; conjugate comprises: i) a targeting component that binds to the binding target; ii) a linker component; iii) a cleavage component; and iv) an oligonucleotide component, wherein the oligonucleotide component comprises a first identifier sequence that identifies the binding target, Para. [0018]), wherein the first single strand oligonucleotide comprises a first nucleotide sequence (conjugate comprises: i) a targeting component that binds to the binding target; ii) a linker component; iii) a cleavage component; and iv) an oligonucleotide component, wherein the oligonucleotide component comprises a first identifier sequence that identifies the binding target, Para. [0018]; the identifier sequence is a single stranded oligonucleotide, Para. [00135]);
Regarding claims 4, 7-9, 13, 14, (ii) a second oligonucleotide conjugate comprising a second single strand oligonucleotide conjugated to an agent, wherein the second single strand oligonucleotide comprises a second nucleotide sequence being complementary to the first nucleotide sequence (a second oligonucleotide conjugate, wherein the second oligonucleotide conjugate comprises a detectable moiety; and an oligonucleotide component, wherein at least a portion of the oligonucleotide component of the second oligonucleotide conjugate is complementary to at least a portion of the oligonucleotide component of the first oligonucleotide conjugate, Para. [0021]; the second identifier sequence is a single stranded, Para. [00136]); wherein the first and second oligonucleotide conjugates form a double-strand oligonucleotide conjugate which comprises a hybridized oligonucleotide bridge region between the first nucleotide sequence and the second nucleotide sequence (a second oligonucleotide component that hybridizes to the first oligonucleotide component of the primary identifier oligonucleotide conjugate, Para. [0030]), whereby the biomolecule and the agent are linked together in the double-strand oligonucleotide conjugate (antibody-drug conjugates comprising (a) a primary identifier oligonucleotide conjugate comprising (i) an antibody that binds to a target on a cell, and (ii) a first oligonucleotide component that is attached to the antibody at the end 3 'end of the first oligonucleotide component, and (b) a secondary therapeutic oligonucleotide conjugate comprising (i) a second oligonucleotide component that hybridizes to the first oligonucleotide component of the primary identifier oligonucleotide conjugate, and (ii) a small molecule that is attached to the 3' end of the second oligonucleotide conjugate, Para. [00162]).
Regarding Claim 2, WO 020 discloses the oligonucleotide conjugate of claim 1, wherein the first nucleotide sequence and the second nucleotide sequence individually comprise a GC rich sequence (first identifier sequence ...second identifier sequence ...55 percent GC rich, Para. [00257]).
Regarding Claim 3, WO 020 discloses the oligonucleotide conjugate of claim 1, wherein the first nucleotide sequence and the second nucleotide sequence individually have substantially no secondary structure (oligonucleotide conjugates, Para. [0036]; See FIG. 4):
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Regarding claims 15, 16, the require chemical linkers are taught:
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Regarding claim 18-21, Figure 21B, demonstrates the recited hybridized structure conjugated to a drug:
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The antibody conjugates include conjugates comprising MMAE, see paragraph [00162] and diagnostic moieties, see paragraph [00157].
The above anticipates the oligonucleotide conjugate embodiments covered in the rejected claims, within the meaning of section 102.
Claim Rejections - 35 USC § 103
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.
Claims 5, 6, 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017190020 (WO 020) in view of WO 2017106283 (WO 283) as evidenced by GenCore version 6.5.2, Copyright (c) 1993 - 2025 Biocceleration Ltd., BEB89691, WO 2017106283, Human HNF1A gene targeting antisense oligonucleotide, SEQ ID 39307 (SEQ ID 39307).
Regarding claims 10 and 11, WO 020 may fail to explicitly teach the first nucleotide sequence and the second nucleotide sequence. However, WO 283 teaches that these oligonucleotide sequences were known, see SEQ ID 39307:
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In this way, those of ordinary skill could have applied the recited oligonucleotides in the manner required and in a predictable fashion for the purposes of obtaining the recited conjugates. Specifically, WO 283 teaches the particular oligonucleotides as part of the purview of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known oligonucleotides, and their hybridized oligonucleotides, as a polynucleotide bridge in the conjugates of WO020 would have yielded a reasonable expectation of success. Accordingly, in the absence of an unexpected result, using the recited oligonucleotides for the purposes of an oligonucleotide bridge in the instant conjugates would have been prima facie obvious.
Regarding claims 5 and 6, WO 020 may fail to teach the recited melting temperatures of the recited oligonucleotides. However, WO 283 demonstrates that these polynucleotides were known and can be used in the instant conjugates, as outlined above. In this way, any observed physical characteristics, such as melting temperature, as recited in claims 5 and 6, would have been a necessary aspect of these oligonucleotides, see MPEP 2112.01 (“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”). Therefore, the recited oligonucleotide melting temperatures would have been prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Janet Epps-Smith, can be reached at telephone number (571)272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646