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 .
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that
There are enumerated amino acid sequences on page 104-105, 110, 115, 116 of the claims that come under the Sequence Rules, but are lacking a Sequence Identifier.
Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 43 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 43 states that the side chain linked conjugate of claim 24 has in vitro, in vivo or ex vivo cell killing ability. Claim 24 requires that the conjugate of claim 24 comprises amanita toxin linked to a cell binding agent. The amanita toxin is toxic to the cell thus bound. Stating that the conjugate has in vitro, in vivo or ex vivo cell killing activity fails to further limit the subject matter of claim 24.. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
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.
Claims 24 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.
(A)A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance,
claims 24 and 25 recite the broad recitation nutrient transport molecule, and the claim also recites a transferrin which is the narrower statement of the range/limitation;
claims 24 and 25 recite the broad recitation “capsid”, and the claim also recites “(viral)” which is the narrower statement of the range/limitation.
claims 24-27 recite the broad recitation hyaluronic acid and the claim also recites “glycosaminoglycan” which is the narrower statement of the range/limitation;
claims 25-27 recite chondroitin sulfate/dermatan sulfate and the claim also recites “(CSGAGs)” which is the narrower statement of the range/limitation;
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
(B)Claim 25 on page 9 and 10 recite multiple instance of parenthetical material which is broader in scope than the term which precedes it. It is unclear if this parenthetical material is a claim limitation, and how it affects the metes and bound of the claim..
Claim 25 on pages 10 and 11, claim 26 on pages 15-17, claim 27 on pages 23, and 24, recite multiple instance of parenthetical material which is broader in scope than the term which precedes it. It is unclear if this parenthetical material is a claim limitation, and how it affects the metes and bounds of the claim..
Claim 38 page 124, recites interleukins (comprising Il-1, Il-2…). It is unclear if the parenthetical information is an actual claim limitations and how it affects the metes and bounds of the claim.
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 40 and 44 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is undue include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re wands, 858 F.2d 731, 737.8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Claim 40 and 44 are drawn in part to pharmaceutical compositions for the prevention of cancer, an autoimmune disease or an infectious disease. When given the broadest reasonable interpretation, this applies to the administration of the pharmaceutical composition to humans or non-experimental animals for the prevention of these diseases. In order for prevention to be carried out the inventive conjugate targeting the particular cancer, pathological autoimmune cell or infectious disease must be present in the circulation of the human or non-experimental animal before the cancer, autoimmune disease or infectious disease occurs. It is noted that the cell binding conjugates have a finite circulation in the blood. Because it is not possible to know when a particular cancer, particular autoimmune disease or infections disease will occur, it is not possible to know when to administer the inventive conjugate having the appropriate targeting agent in order to prevent said disease. The specification fails to address this problem, Thus, one of skill in the art would be subject to undue experimentation in order to administer the pharmaceutical composition for the prevention of cancer, autoimmune disease or infectious disease.
.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 24-46, 48-is/are rejected under 35 U.S.C. 103 as being obvious over Gallo et al (WO2019/057964) in view of Zhao et al (WO2019/127607).
Gallo et al teach a side-chain linkaged conjugates comprising an anti-PSMA antibody as targeting agent:
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(abstract and pages 39-41). Gallo et al teach that the conjugates are used for the treatment of cancer in a patient particularly breast, pancreatic, cholangiocarcinoma, colorectal, lung, prostate, ovarian, stomach, kidney melanoma, leukemia and lymphoma cancers (paragraph [00128]) which meets the limitations of claim 24 for a cell binding agent which is an antibody, a cell binding agent capable of targeting a tumor cell in claim 38, wherein the tumor cells are lymphoma cells, renal cells, breast cancer cells, prostate cancer cells, ovaria cancer cells, colorectal cancer cells and gastric cancer cells in claim 39. The adducts at R5 and R10 of Gallo et al meet the limitations of “D” in claim 29. Gallo et al teach a pharmaceutical composition comprising the inventive conjugates which meets the limitations of claim 40. Gallo et al teach the attachment of the branching linker to position R10 of amatoxin (structures 1-3, above) and position R5 of amatoxin (structures 4-6, above). Gallo et al do not teach the same chemical formulas for the main linker attached to the amatoxin or the side chain branching linker attached to the main linker.
Zhao et al teach tubulysin analogs conjugated to cell binding molecule (abstract) with the same linkers as the instant claims. Zhao et al teach a side-chain linkaged conjugate having formula I (page 4); the branched side-chain of formula 1-q1 (page 6), which meet those limitations in claims 24. Zhao et al teach the side-chain linkaged conjugate of formula III on page 8, which meet those limitations in claim 25. Zhao et al teach the drug-side chain-linkage of formula III can readily react to form the conjugate of formula I (page 8), which meet those limitations of claim 26. Zhao et al teach the drug-side chain linkaged conjugate of formula V which can readily react to form the conjugate of formula III (page 94) which meet those limitations of claim 27. Zhao et al teach that the side-chain linkaged conjugates of claim 34 comprise the moieties of instant claim 30 (pages 39-41) which meet those limitation of claim 30. Zhao et al teach that the side-chain linker of claim 24 comprises the moieties required in instant claim 31 (pages 41-44). Zhao et al teach that the side-chain linker comprises the moieties of instant claim 37 (claim 14 of ‘607). Zhao et al teach that the pharmaceutical composition comprises the formulation of claim 41 (claim 18 of ‘607). Zhao et al teach that the pharmaceutical composition is packaged in a vial, bottle, pre-filled syringe, pre-filled autoinjector syringe in the form of a liquid of lyophilized solid (claim 19 of ‘607) thus meeting the limitation of claim 42. Zhao et al teach that the side-chain-linked conjugates have in vitro, in vivo or ex-vivo cell -killing activity (claim 20 of ‘607) thus meeting the limitations of instant claim 43.
Zhao et al teach the concurrent administration of the inventive pharmaceutical composition with a chemotherapy agent, a radiation agent, an immunotherapy agent, an or another conjugate for synergistic treatment or prevention of a cancer (claim 21 of ‘607) which meets the limitations of claim 44. Zhao et al teach the further limitations of dependent claim 45 (claim 22 of ‘607) and the further limitations of instant claim 44 (claim 23 of ‘607). Zhao et al teach the side-chain linkaged compound of claim 25 comprises the Lv1 moieties of instant claim 38 (page 76 of ‘607)
Zhao et al teach that the long-side chain branch can prevent the antibody-drug-conjugate from hydrolysis by a proteinase or esterase resulting in more ability of the conjugate in circulation (page 3, lines 8-11 of the middle paragraph). Zhao et al teach that the long-branched side-chain linker can prolong the half-life of the conjugate during targeted delivery and minimize exposure to non-target cels, tissue or organs resulting in less off-target toxicity (page 4, lines 21-24).
It would have been prima facie obvious at the time prior to the effective filing date to substitute the formulas used by Zhao et al in the side-chain linkaged conjugates for the specific side-chain linkages used by Gallo et al. One of skill in the art would have been motivate to do so by the teachings of Zhao et al that the particular side-chain linkages resulted in resistance of the conjugate to proteinases and esterases while circulating in the blood, resulting in greater stability and less off-target toxicity.
Regarding claims 32-35, applying the formula for the side chain linkers of Zhao et al to substitute for the side-chain linkers of Gallo et al would lead on of skill in the art to the R5 and R10 amatoxin side chain linker conjugates of structures a-11, a-12, a-15, a-16, a-37, a-38, a-39 and a-40 of claim 32; structure b-01 of claim 33; structures c-11 and c14-c16 of claim 34 and structures d-03 and d-04 of claim 35.
All claims are rejected.
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643