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 without traverse in the reply filed on 2/5/2026 is acknowledged:
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Claims 1, 2, 4, 5, 7, 8, 10, 12-14, 16, 18 and 19 read on the elected invention and are treated on the merits, below. Claims 20, 22-27, 29, 31 are withdrawn from consideration as exclusively covering a non-elected invention.
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.
The instant application contains polynucleotide and/or polypeptide sequences. Applicant is required to review the Specification for compliance with the above.
Specification
The use trade names or marks used in commerce, has been noted in this application. See for example Sephadex, in Example 3-6 ADC-6.
The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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, 4, 7, 10, 12-14, 16 and 18 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 antibody-drug conjugates (ADC’s) comprising an anti-TROP-2 antibody or an antigen-binding fragment thereof.
Here, a genus of antibodies that can bind to TROP-2 or antigen-binding fragments thereof lack written description because:
1) The specification lacks a representative number of species that satisfies the entirety of the genus; and
2) The recited functional definition of the antibody does not describe the claimed invention.
Firstly, 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”).
1) The specification lacks a representative number of antibody species that satisfies the entirety of the genus.
Specifically, with regard to anti-TROP-2 antibody or an antigen-binding fragment thereof, 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 any particular compound encompassed by the claims. To the contrary, the specification states that the claimed compounds are derived from the recited substituents.
However, in view of the above, the specification does not provide adequate written description of the anti-TROP-2 antibody. Specifically, Applicant fails to disclose any other antibodies, besides those described by specific SEQ ID NO’s in the specification and claims, and in relation to the above, these disclosed species do not represent the substantial variety required by the genus of anti-TROP-2 antibodies.
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)).
2) The recited functional definition of the anti-TROP-2 antibody or antigen-binding fragment thereof does not describe the claimed invention.
Here, the genus of antibodies cannot be adequately described by functional characteristics of preferential binding, even where there is disclosed or known correlations between structure and function.
The Examiner recognizes that the target, TROP-2, may be fully characterized. Previously, disclosing a bonding target, such as TROP-2, satisfies the written description requirement for a claim to an antibody or protein that binds the target. The Federal Circuit's decisions in Enzo Biochem v. Gen-Probe, Inc., 323 F.3d 956, 964 (Fed. Cir. 2002) and Noelle v. Lederman, 355 F. 3d 1341 (Fed. Cir. 2004) which purportedly set forth what has been called the "newly characterized antigen" test. Also, the PTO's Written Description Training Materials Revision dated March 25, 2008, provide an example (Example 13) embodying the test set forth in Enzo and Noelle.
However, reliance on Enzo and Noelle is misplaced. While the court in Noelle did discuss what is referred to as the "newly characterized antigen" test, the Federal Circuit has recently rejected such a test. Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378-79 (Fed. Cir. 2017). At issue in Amgen was the district court's jury instruction which read:
In the case of a claim to antibodies, the correlation between structure and function may also be satisfied by the disclosure of a newly characterized antigen by its structure, formula, chemical name, or physical properties if you find that the level of skill and knowledge in the art of antibodies at the time of filing was such that the production of antibodies against such an antigen was conventional and routine.
Id. at 1376. The Federal Circuit concluded that the instruction was "not legally sound and [was] not based on any binding precedent." Id. In reaching its conclusion the Federal Circuit reviewed the cases which purported to set forth the newly characterized antigen test including Noelle. Id. at 1376-77. The court concluded that in each of the prior cases the reference to the newly characterized antigen test was dicta and not binding precedent. Id.
The Federal Circuit went on to find that the newly characterized antigen test ran afoul of the Federal Circuit's precedent in Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). Id. at 1378. The court noted that the focus of the inquiry is whether the written description contains enough information about the claimed products. Id. The court held that describing the antigens, which was not the claimed invention, did not satisfy the written description requirement when (“it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. See, e.g., J.A. 1241 (549:5-16) (Appellants' expert Dr. Eck testifying that knowing "that an antibody binds to a particular amino acid... does not tell you anything at all about the structure of the antibody [emphasis applied]"); J.A. 1314 (836:9-11) (Appellees' expert Dr. Petsko being informed of Dr. Eck's testimony and responding that "[m]y opinion is that [he's] right"); Centocor, 636 F.3d at 1352 (analogizing the antibody antigen relationship as searching for a key "on a ring with a million keys on it") (internal citations and quotation marks omitted).
In a memo issued in February 2018, USPTO, Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials, Feb. 22, 2018 (available at https://www.usnto.gov/sites/defauH/files/documents/amgen 22feb2018.pdf) the PTO issued a clarification regarding the law of written description as it applies to antibodies stating:
In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
The Memo goes on to state that
"Examples in the 2008 Written Description Training Materials Are Outdated." and should NOT be relied upon as reflecting the current state of the law. Id. at 2. The Memo explains that
USPTO personnel should continue to follow the guidance in the MPEP regarding written description (see, e.g., MPEP 2161.01 and 2163 ), except insofar as MPEP 2163 indicates that disclosure of a fully characterized antigen may provide written descriptive support of an antibody to that antigen.
Id.
The instant claims present the same deficiency as the claims in Amgen where there is no evidence that knowledge of the chemical structure of TROP-2 gives the required kind of structure-identifying information about the corresponding peptides that it binds. As in Amgen, the instant claims attempt to describe TROP-2-binding antibodies by describing the target to which the peptides bind. Moreover, there is nothing else in the disclosure that describes the peptides as required by the test set forth in Ariad.
Moreover, regard to the functional definition the antibody, 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 antibodies to see if the antibodies can perform the required binding of TROP-2. In this connection, the specification contains no generic structural or specific functional characteristics of those antibodies which bind ofCS, besides those peptides corresponding to the disclosed SEQ ID NO’s, 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.”).
Accordingly, the specification lacks adequate written description for the recited anti-TROP-2 antibody or antigen-binding fragments thereof.
Claims 5 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 5 covers conjugates wherein the anti-TROP-2 antibody or antigen-binding fragments thereof have a heavy chain variable region which has at least 90% identity to SEQ ID NO: 3, and/or a light chain variable region which has at least 90% identity to SEQ ID NO: 4.
How much homology is required to claim a variant of a known sequence when the function of a gene product was recited in the claims was addressed in Ex parte Livshits (Appeal 2013-001807; US Patent Application 11/106,455)
https://www.bradley.com/insights/publications/2016/02/how-much-homology-is-enough-under--112
Un that case, the PTAB agreed with the Examiner that a PHOSITA could envision sequences that met the percent identity requirement and hybridized under the recited conditions to SEQ ID NO:3.
Further, the Examiner admitted that by using conservative substitutions, a PHOSITA could likely envision a DNA sequence that encoded a polypeptide having the same tertiary structure as the polypeptide encoded by SEQ ID NO:3.
However, the PTAB found there was no teaching that the conservation of structure (whether in the DNA or encoded polypeptide) would be a surrogate for conservation of the function claimed (over-expression of L-amino acids in the culture medium).
In other words, PTAB wanted some teaching as to which of the 5 percent of residues of the in the recited single domain antibody could be altered while still conserving the function of the encoded polypeptide.
Here, the specification demonstrates the recited function for the anti-TROP-2 antibodies encoded by specific SEQ ID NO’s of the heavy and light chain variable regions, but offers no teaching as to what fragments of the recited variable regions were critical for conservation of the recited function and which regions could be modified.
Here, the specification leaves it to others to discover the nature and scope of substitutions, deletions, and insertions that can be made to arrive at a 90% sequence identity that additionally allows for recited anti-TROP-2 activity.
The applicants may attempt to use BLAST homology data to argue that a PHOSITA would be able to address the issue, but the evidence is accorded little weight and characterized as an “invitation to experiment” by the PTAB in Livshits.
Even though DNA/polypeptides could be envisioned by the PHOSTIA could be easily tested as set forth in the specification for conservation of the recited function, this was not enough to describe the structure so that a PHOSITA could determine beforehand whether or not a particular structure meets the functional requirements.
Here, a PHOSITA cannot determine if the claimed antibodies with the recited % identity accomplish the recited function from the specification itself in order to meet the written description requirement.
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 1, 2, 4, 5, 7, 8, 10, 12-14, 16, 18 and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The rejected claims recite antigen-binding fragments of anti-TROP-2 antibodies. Besides those SEQ ID’s taught as variable fragments or CDR’s that specifically bind TROP-2, it is unclear what other fragments Applicant intends to cover by antigen-binding fragments of an anti-TROP-2 antibody.
The claims are replete with “preferably”. It is unclear if Applicant intends the claims to be limited to the preferred embodiments.
In claim 2, it is unclear what fragments Applicant considers HCDR1, a HCDR2 and a HCDR3 of a heavy chain variable region set forth in SEQ ID NO: 3. Similalry, it is unclear what fragments Applicant considers LCDR1, a LCDR2 and a LCDR3 of a light chain variable region set forth in SEQ ID NO: 4.
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 1, 4, 10, 12-14, 16, 18 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 20170035906 based on an application by Naito et al. (Naito) in view of:
Kushner et al., Canadian Journal of Physiology and Pharmacology (1999), 77(2), 79-88;
US 6,603,008;
US 6,221,335;
US 20070082929;
US 20070197695;
US 7,517,990;
Tonn, Biological Mass Spectrometry Volume 22 Issue 11, Pages 633 – 642 (1993);
Haskins, Biomedical Spectrometry Volume 9 Issue 7, Pages 269 – 277 (1982);
Wolen, Journal of Clinical Pharmacology 1986; 26: 419-424;
Browne, Journal of Clinical Pharmacology 1998; 38: 213-220;
Baillie, Pharmacology Rev.1981; 33: 81-132;
US 6,440,710; and
Gouyette, Biomedical and Environmental Mass Spectrometry, Vol. 15, 243-247 (1988); in further view of Starodub et al., Abstract, J Clin Oncol 34, 8559(2016) (Starodub) and Goldenberg et al., Oncotarget. 2015 Jun 18;6(26):22496–22512 (Goldenberg).
Regarding claims 1, 4, 10, 12-14, 16, 18, Naito teaches the following linker-drug constructs used in ADC’s for cancer therapy:
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The rejected claims cover deuterated alkyl groups for R1 and R2 which are not specifically taught by Naito. However, it is for that proposition that the examiner joins the secondary references which teach that such modified compounds are obvious, for two separate reasons:
First, one is motivated to prepare deuterated versions of drugs to obtain a version with better pharmaceutical properties.
For example, Kushner et al., Canadian Journal of Physiology and Pharmacology (1999), 77(2), 79-88 discloses that it is advantageous to deuterate pharmaceutical compounds because isotopic enhancement of known drugs leads to enhancement of efficacy of known pharmaceuticals by improving the activity and increased duration of actions compared to the non-deuterated (non-isotopically enhanced) known drugs. Kushner describes that the deuterated forms of drugs often have different actions than the protonated forms. Some deuterated drugs show different transport processes. Most are more resistant to metabolic changes, especially those changes mediated by cytochrome P 450 systems. Deuteration may also change the pathway of drug metabolism (metabolic switching). Changed metabolism may lead to increased duration of action and lower toxicity. It may also lead to lower activity, if the drug is normally changed to the active form in vivo. Deuteration can also lower the genotoxicity of therapeutic compounds. Deuteration increases effectiveness of compounds by preventing their breakdown by target microorganisms. See page 83+.
US 6,603,008 teaches "[S]ubstitution with heavier isotopes such as deuterium, i.e. 2H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances" (see col. 6, lines 59-67 and col. 7, lines 11-16).
US 6,221,335 teaches that “by deuterating drugs, we have likely … increased the lipophilic nature of the molecule” and, via the deuterium isotope effect, produced a derivative “less easily cleaved by metabolic (or destructive) processes. Hence, the elimination half life of the drug is prolonged and the drug's therapeutic effects are increased.”
US 20070082929, paragraph 0014 states, “Deuteration of pharmaceuticals to improve pharmacokinetics (PK), pharmacodynamics (PD), and toxicity profiles, has been demonstrated previously with some classes of drugs.
US 20070197695 states, “Deuteration can yield pharmaceuticals having improved bioavailability and reduced the toxicity.”
US 7,517,990 states, “a deuterated compound is very useful in elucidation of reaction mechanism and substance metabolism and used widely as a labeled compound. Said compound is also known to be useful as drugs, pesticides … and the like due to change in stability and property itself by isotope effect thereof.”
Second, and as an alternative branch, one is motivated to prepare deuterated versions of drugs, which can be used to obtain valuable information about how the un-deuterated drug or closely related drugs act in the body. Note the quotation for US 7517990 above. For example:
Tonn, Biological Mass Spectrometry Volume 22 Issue 11, Pages 633 – 642 (1993) states “Pharmacokinetic studies employing stable isotope labeled drugs… offer many advantages over the more conventional use of unlabeled drugs… A pharmacokinetic study in which a labeled and an unlabeled drug are simultaneously and independently … is advantageous since it reduces to inter-day variability in the measured pharmacokinetic parameters. The advantages of this approach include an increase in the statistical power of the study, yielding an overall reduction in the number of study subjects, and also a diminished risk due to a reduction in the exposures to the drug. In addition, the overall time required to conduct experiments, and hence the number of samples to be collected for analysis, may also be substantially reduced.” The reference study is an example of just that. Thus, one is motivated to prepare deuterated drugs to gain these explicitly set forth advantages.
Haskins, Biomedical Spectrometry Volume 9 Issue 7, Pages 269 – 277 (1982) surveys the application of stable isotopes in biomedical research in several areas. For example, in stable isotope dilution assays, it notes that deuterium is “is the best heavy isotope for this work”. Also, the section on the use of stable isotopes in chronic administration studies lists only deuterium isotopes.
Wolen, Journal of Clinical Pharmacology 1986; 26: 419-424, noting that the lack of toxicity for deuterium makes it “ideally suited for human studies” (abstract) concludes that “the application of stable isotope methodology to the problems of bioavailability and bioequivalence have proved extremely versatile and useful. The technique is simple and powerful and results in extremely low risk to the subject.” (see page 423) Thus, one is motivated to prepare deuterated drugs to gain these advantages.
Browne, Journal of Clinical Pharmacology1998; 38: 213-220 quantifies the advantage of using stable isotope labeled drugs to, for example, identify metabolites, to evaluate drug interactions, and to measure absolute bioavailability. Compared with standard methods which do not use isotopically labeled drugs, there is a cost reduction of 23% and a reduction in 36% in terms of the number of subjected needed. This again provides a strong motivation, to obtain these advantages.
Baillie, Pharmacology Rev.1981; 33: 81-132 is a useful review of the use of stable isotopes. For example, pages 108-110 (section III C1) discuss the use of deuterated compounds in mechanism and toxicology studies, on drugs such as cyclophosphamide, iproniazid, and ibuprofen. Pages 114-117 (section II C 4) discuss the use the deuterium isotope effect to understand the metabolism of drugs such as chloroform and other inhaled anesthetics, furosemide, and caffeine.
US 6,440,710 states, “Deuterium- and tritium-labeled organic compounds have become increasingly important for the role they play in structure determination, mechanistic studies, elucidation of biosynthetic pathways and in biochemical studies.”
Gouyette, Biomedical and Environmental Mass Spectrometry, Vol. 15, 243-247 (1988), gives an example with the anti-cancer drug Elliptinium. The reference notes, “New derivatives in the ellipticine series are under preclinical and clinical development. In order to study the fate of those molecules, it was decided that a standard molecule of this family of intercalating agents be labelled with stable isotopes which might be used in man without any problem of radioprotection or irradiation. Therefore, in a first step, elliptinium was labelled with three deuterium atoms, then injected intravenously into rats…” In this way, they were “able to confirm the presence of unchanged drug in urine and in bile” and identify two metabolites. This information provided about ellipticine is relevant to other derivatives in the ellipticine series.
Hence, it is clear that under either of these two prongs, “a person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and that there would have been a reasonable expectation of success." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 80 USPQ2d 1641, 1645.
Moreover, given that there is always a need to enhance the pharmacological effects of a compound (e.g. increased in vivo half-life) without significantly altering its basic chemical structure (first branch), or that there is always a need to reduce the time, cost, risk, and statistical imprecision of pharmacokinetic studies (e.g. measure bioavailability or identify metabolites) (second branch), and that there is only a limited number of ways that this can be done, it would be obvious to pursue a potential solution that has a reasonable expectation of success. See e.g. KSR International Co. v. Teleflex Inc., 1385, 1397; Pfizer, Inc. v. Apotex, Inc., 82 USPQ2d 1321; Alza Corp. v. Mylan Laboratories, Inc., 80 USPQ2d 1001; In re Kubin, 90 USPQ2d 1417; In re O’Farrell, 7 USPQ2d 1673, 1681; In re Eli Lilly & Co., 14 USPQ2d 1741; In re Ball Corp., 18 USPQ2d 1491.
In addition, it is clear under both branches that deuteration per se is a known improvement technique for getting a more useful version of the pharmaceutical, and that the improvement is of a predictable nature, as is seen by the success reported in the various secondary references. Thus, it would have been obvious to one of ordinary skill in the pharmaceutical art to have applied this known improvement technique in the same way to the compound of the primary reference to obtain the results reasonably predictable from the secondary references. See, e.g., KSR International Co. v. Teleflex Inc., 1385, 1396; Ruiz v. AB Chance Co., 69 USPQ2d 1686; In re Nilssen, 7 USPQ2d 1500.
Accordingly, the linker-drug constructs are deemed obvious.
The primary references may not explicitly teach conjugates with anti-TROP-2 antibodies. However, the secondary references demonstrate that Trop-2 is a transmembrane glycoprotein overexpressed in many solid tumors (e.g., breast, lung, urothelial), making it an ideal target for antibody-drug conjugates. It is for that proposition that the rejection joins the secondary references.
See Starodub (“Sacituzumab govitecan (IMMU-132) is a novel ADC comprising SN-38, the active metabolite of the topoisomerase inhibitor, irinotecan, conjugated to an anti-Trop-2 humanized antibody. Its uniquely very high drug:antibody ratio of 7.6 allows delivering up to 136-fold more SN-38 than its parent drug, irinotecan, in a human cancer xenograft. The mAb and ADC are immunotherapeutic in vitro (ADCC). Expression of Trop-2 is increased in most epithelial cancers (>80%), including SCLC.”).
See Goldenberg (“Trop-2 is a novel target for ADC therapy because of its high expression by many solid cancers… A novel target in multiple solid cancers for an ADC is trophoblast cell-surface antigen, or Trop-2, also known as tumor-associated calcium signal transducer (TACSTD2), epithelial glycoprotein-1 (EGP-1), gastrointestinal tumor-associated antigen (GA733-1), and surface marker 1 (M1S1)”).
In this way, those of ordinary skill could have applied the recited anti-TROP-2-antibodies in the manner required and in a predictable fashion for the purposes of providing the instant ADC’s. As outlined above, the primary references teach that ADC’s with the core linker-drugs were known. The secondary references are added for the proposition that the recited targeting antibodies, i.e., anti-TROP-2, are applicable to these ADC’s. Specifically, the secondary references teach that the particular known technique of using anti-TROP-2 antibodies in ADC’s was recognized as part of the ordinary capabilities of one skilled in the art. In this manner those of ordinary skill would have recognized that applying the known technique to ADC’s, such as those taught by the primary references, would have yielded predictable results. Accordingly, using the recited anti-TROP-2 antibodies for the purposes of preparing the instant ADC’s would have been prima facie obvious.
Claims 1, 4, 10, 12-14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020063673 and counterparts US 12377163 and U.S. Publication No. 20210347894 based on an application by Ying et al. (collectively “Ying”) in view of Starodub et al., Abstract, J Clin Oncol 34, 8559(2016) (Starodub) and Goldenberg et al., Oncotarget. 2015 Jun 18;6(26):22496–22512 (Goldenberg).
References to Ying are based on the U.S. Publication.
Regarding claims 1, 4, 10, 12-14 and 16, Ying discloses anti-B7H3 antibody-drug conjugates for cancer treatment:
See for example:
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See pages 7+.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record.
Namely, unlike pre-AIA law, the AIA provides that a foreign priority date can be the effective filing date of a claimed invention. The foreign priority date is the effective filing date of the claimed invention IF
-the foreign application supports the claimed invention under 112(a), AND
-the applicant has perfected the right of priority by providing:
a certified copy of the priority application, and
a translation of the priority application (if not in English).
When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate.
The primary references may not explicitly teach conjugates with anti-TROP-2 antibodies. However, the secondary references demonstrate that Trop-2 is a transmembrane glycoprotein overexpressed in many solid tumors (e.g., breast, lung, urothelial), making it an ideal target for antibody-drug conjugates. It is for that proposition that the rejection joins the secondary references.
See Starodub (“Sacituzumab govitecan (IMMU-132) is a novel ADC comprising SN-38, the active metabolite of the topoisomerase inhibitor, irinotecan, conjugated to an anti-Trop-2 humanized antibody. Its uniquely very high drug:antibody ratio of 7.6 allows delivering up to 136-fold more SN-38 than its parent drug, irinotecan, in a human cancer xenograft. The mAb and ADC are immunotherapeutic in vitro (ADCC). Expression of Trop-2 is increased in most epithelial cancers (>80%), including SCLC.”).
See Goldenberg (“Trop-2 is a novel target for ADC therapy because of its high expression by many solid cancers… A novel target in multiple solid cancers for an ADC is trophoblast cell-surface antigen, or Trop-2, also known as tumor-associated calcium signal transducer (TACSTD2), epithelial glycoprotein-1 (EGP-1), gastrointestinal tumor-associated antigen (GA733-1), and surface marker 1 (M1S1)”).
In this way, those of ordinary skill could have applied the recited anti-TROP-2-antibodies in the manner required and in a predictable fashion for the purposes of providing the instant ADC’s. As outlined above, the primary references teach that ADC’s with the core linker-drugs were known. The secondary references are added for the proposition that the recited targeting antibodies, i.e., anti-TROP-2, are applicable to these ADC’s. Specifically, the secondary references teach that the particular known technique of using anti-TROP-2 antibodies in ADC’s was recognized as part of the ordinary capabilities of one skilled in the art. In this manner those of ordinary skill would have recognized that applying the known technique to ADC’s, such as those taught by the primary references, would have yielded predictable results. Accordingly, using the recited anti-TROP-2 antibodies for the purposes of preparing the instant ADC’s would have been prima facie obvious.
Claims 1, 4, 10, 12-14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over CN 111689980 (CN 980) in view of Starodub et al., Abstract, J Clin Oncol 34, 8559(2016) (Starodub) and Goldenberg et al., Oncotarget. 2015 Jun 18;6(26):22496–22512 (Goldenberg).
Regarding claims 1, 4, 10, 12-14 and 16, CN 980 teaches the following linker-drugs:
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See page 14.
The primary references may not explicitly teach conjugates with anti-TROP-2 antibodies. However, the secondary references demonstrate that Trop-2 is a transmembrane glycoprotein overexpressed in many solid tumors (e.g., breast, lung, urothelial), making it an ideal target for antibody-drug conjugates. It is for that proposition that the rejection joins the secondary references.
See Starodub (“Sacituzumab govitecan (IMMU-132) is a novel ADC comprising SN-38, the active metabolite of the topoisomerase inhibitor, irinotecan, conjugated to an anti-Trop-2 humanized antibody. Its uniquely very high drug:antibody ratio of 7.6 allows delivering up to 136-fold more SN-38 than its parent drug, irinotecan, in a human cancer xenograft. The mAb and ADC are immunotherapeutic in vitro (ADCC). Expression of Trop-2 is increased in most epithelial cancers (>80%), including SCLC.”).
See Goldenberg (“Trop-2 is a novel target for ADC therapy because of its high expression by many solid cancers… A novel target in multiple solid cancers for an ADC is trophoblast cell-surface antigen, or Trop-2, also known as tumor-associated calcium signal transducer (TACSTD2), epithelial glycoprotein-1 (EGP-1), gastrointestinal tumor-associated antigen (GA733-1), and surface marker 1 (M1S1)”).
In this way, those of ordinary skill could have applied the recited anti-TROP-2-antibodies in the manner required and in a predictable fashion for the purposes of providing the instant ADC’s. As outlined above, the primary references teach that ADC’s with the core linker-drugs were known. The secondary references are added for the proposition that the recited targeting antibodies, i.e., anti-TROP-2, are applicable to these ADC’s. Specifically, the secondary references teach that the particular known technique of using anti-TROP-2 antibodies in ADC’s was recognized as part of the ordinary capabilities of one skilled in the art. In this manner those of ordinary skill would have recognized that applying the known technique to ADC’s, such as those taught by the primary references, would have yielded predictable results. Accordingly, using the recited anti-TROP-2 antibodies for the purposes of preparing the instant ADC’s would have been prima facie obvious.
Claims 1, 4, 10, 12-14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020244657 and counterpart U.S. Publication No. 20230072897 based on an application by Hua et al. (collectively “Hua”) in view of Starodub et al., Abstract, J Clin Oncol 34, 8559(2016) (Starodub) and Goldenberg et al., Oncotarget. 2015 Jun 18;6(26):22496–22512 (Goldenberg).
References to Hua are based on the U.S. Publication.
Regarding claims 1, 4, 10, 12-14 and 16, Hua discloses anti-B7H4 antibody-drug conjugates for cancer treatment:
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Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record.
Namely, unlike pre-AIA law, the AIA provides that a foreign priority date can be the effective filing date of a claimed invention. The foreign priority date is the effective filing date of the claimed invention IF
-the foreign application supports the claimed invention under 112(a), AND
-the applicant has perfected the right of priority by providing:
a certified copy of the priority application, and
a translation of the priority application (if not in English).
When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate.
The primary references may not explicitly teach conjugates with anti-TROP-2 antibodies. However, the secondary references demonstrate that Trop-2 is a transmembrane glycoprotein overexpressed in many solid tumors (e.g., breast, lung, urothelial), making it an ideal target for antibody-drug conjugates. It is for that proposition that the rejection joins the secondary references.
See Starodub (“Sacituzumab govitecan (IMMU-132) is a novel ADC comprising SN-38, the active metabolite of the topoisomerase inhibitor, irinotecan, conjugated to an anti-Trop-2 humanized antibody. Its uniquely very high drug:antibody ratio of 7.6 allows delivering up to 136-fold more SN-38 than its parent drug, irinotecan, in a human cancer xenograft. The mAb and ADC are immunotherapeutic in vitro (ADCC). Expression of Trop-2 is increased in most epithelial cancers (>80%), including SCLC.”).
See Goldenberg (“Trop-2 is a novel target for ADC therapy because of its high expression by many solid cancers… A novel target in multiple solid cancers for an ADC is trophoblast cell-surface antigen, or Trop-2, also known as tumor-associated calcium signal transducer (TACSTD2), epithelial glycoprotein-1 (EGP-1), gastrointestinal tumor-associated antigen (GA733-1), and surface marker 1 (M1S1)”).
In this way, those of ordinary skill could have applied the recited anti-TROP-2-antibodies in the manner required and in a predictable fashion for the purposes of providing the instant ADC’s. As outlined above, the primary references teach that ADC’s with the core linker-drugs were known. The secondary references are added for the proposition that the recited targeting antibodies, i.e., anti-TROP-2, are applicable to these ADC’s. Specifically, the secondary references teach that the particular known technique of using anti-TROP-2 antibodies in ADC’s was recognized as part of the ordinary capabilities of one skilled in the art. In this manner those of ordinary skill would have recognized that applying the known technique to ADC’s, such as those taught by the primary references, would have yielded predictable results. Accordingly, using the recited anti-TROP-2 antibodies for the purposes of preparing the instant ADC’s would have been prima facie obvious.
Claims 1, 4, 10, 12-14, 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021115426 and counterpart U.S. Publication No. 20230054458 based on an application by Yang et al. (collectively “Yang”) in view of Starodub et al., Abstract, J Clin Oncol 34, 8559(2016) (Starodub) and Goldenberg et al., Oncotarget. 2015 Jun 18;6(26):22496–22512 (Goldenberg).
References to Yang are based on the U.S. Publication.
Regarding claims 1, 4, 10, 12-14, 16 and 18, Yang discloses anti-claudin18.2 antibody-drug conjugates for cancer treatment:
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See pages 6+.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record.
Namely, unlike pre-AIA law, the AIA provides that a foreign priority date can be the effective filing date of a claimed invention. The foreign priority date is the effective filing date of the claimed invention IF
-the foreign application supports the claimed invention under 112(a), AND
-the applicant has perfected the right of priority by providing:
a certified copy of the priority application, and
a translation of the priority application (if not in English).
When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate.
The primary references may not explicitly teach conjugates with anti-TROP-2 antibodies. However, the secondary references demonstrate that Trop-2 is a transmembrane glycoprotein overexpressed in many solid tumors (e.g., breast, lung, urothelial), making it an ideal target for antibody-drug conjugates. It is for that proposition that the rejection joins the secondary references.
See Starodub (“Sacituzumab govitecan (IMMU-132) is a novel ADC comprising SN-38, the active metabolite of the topoisomerase inhibitor, irinotecan, conjugated to an anti-Trop-2 humanized antibody. Its uniquely very high drug:antibody ratio of 7.6 allows delivering up to 136-fold more SN-38 than its parent drug, irinotecan, in a human cancer xenograft. The mAb and ADC are immunotherapeutic in vitro (ADCC). Expression of Trop-2 is increased in most epithelial cancers (>80%), including SCLC.”).
See Goldenberg (“Trop-2 is a novel target for ADC therapy because of its high expression by many solid cancers… A novel target in multiple solid cancers for an ADC is trophoblast cell-surface antigen, or Trop-2, also known as tumor-associated calcium signal transducer (TACSTD2), epithelial glycoprotein-1 (EGP-1), gastrointestinal tumor-associated antigen (GA733-1), and surface marker 1 (M1S1)”).
In this way, those of ordinary skill could have applied the recited anti-TROP-2-antibodies in the manner required and in a predictable fashion for the purposes of providing the instant ADC’s. As outlined above, the primary references teach that ADC’s with the core linker-drugs were known. The secondary references are added for the proposition that the recited targeting antibodies, i.e., anti-TROP-2, are applicable to these ADC’s. Specifically, the secondary references teach that the particular known technique of using anti-TROP-2 antibodies in ADC’s was recognized as part of the ordinary capabilities of one skilled in the art. In this manner those of ordinary skill would have recognized that applying the known technique to ADC’s, such as those taught by the primary references, would have yielded predictable results. Accordingly, using the recited anti-TROP-2 antibodies for the purposes of preparing the instant ADC’s would have been prima facie obvious.
Claims 1, 4, 10, 12-14, 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021121204 and counterpart U.S. Publication No. 20230055408 based on an application by Ying et al. (collectively “Ying”) in view of Starodub et al., Abstract, J Clin Oncol 34, 8559(2016) (Starodub) and Goldenberg et al., Oncotarget. 2015 Jun 18;6(26):22496–22512 (Goldenberg).
References to Ying are based on the U.S. Publication.
Regarding claims 1, 4, 10, 12-14, 16 and 18, Ying discloses anti-CEA antibody-drug conjugates for cancer treatment:
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See pages 9+.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record.
Namely, unlike pre-AIA law, the AIA provides that a foreign priority date can be the effective filing date of a claimed invention. The foreign priority date is the effective filing date of the claimed invention IF
-the foreign application supports the claimed invention under 112(a), AND
-the applicant has perfected the right of priority by providing:
a certified copy of the priority application, and
a translation of the priority application (if not in English).
When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate.
The primary references may not explicitly teach conjugates with anti-TROP-2 antibodies. However, the secondary references demonstrate that Trop-2 is a transmembrane glycoprotein overexpressed in many solid tumors (e.g., breast, lung, urothelial), making it an ideal target for antibody-drug conjugates. It is for that proposition that the rejection joins the secondary references.
See Starodub (“Sacituzumab govitecan (IMMU-132) is a novel ADC comprising SN-38, the active metabolite of the topoisomerase inhibitor, irinotecan, conjugated to an anti-Trop-2 humanized antibody. Its uniquely very high drug:antibody ratio of 7.6 allows delivering up to 136-fold more SN-38 than its parent drug, irinotecan, in a human cancer xenograft. The mAb and ADC are immunotherapeutic in vitro (ADCC). Expression of Trop-2 is increased in most epithelial cancers (>80%), including SCLC.”).
See Goldenberg (“Trop-2 is a novel target for ADC therapy because of its high expression by many solid cancers… A novel target in multiple solid cancers for an ADC is trophoblast cell-surface antigen, or Trop-2, also known as tumor-associated calcium signal transducer (TACSTD2), epithelial glycoprotein-1 (EGP-1), gastrointestinal tumor-associated antigen (GA733-1), and surface marker 1 (M1S1)”).
In this way, those of ordinary skill could have applied the recited anti-TROP-2-antibodies in the manner required and in a predictable fashion for the purposes of providing the instant ADC’s. As outlined above, the primary references teach that ADC’s with the core linker-drugs were known. The secondary references are added for the proposition that the recited targeting antibodies, i.e., anti-TROP-2, are applicable to these ADC’s. Specifically, the secondary references teach that the particular known technique of using anti-TROP-2 antibodies in ADC’s was recognized as part of the ordinary capabilities of one skilled in the art. In this manner those of ordinary skill would have recognized that applying the known technique to ADC’s, such as those taught by the primary references, would have yielded predictable results. Accordingly, using the recited anti-TROP-2 antibodies for the purposes of preparing the instant ADC’s would have been prima facie obvious.
Claims 1, 4, 10, 12-14, 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021190480 (WO 480) in view of Starodub et al., Abstract, J Clin Oncol 34, 8559(2016) (Starodub) and Goldenberg et al., Oncotarget. 2015 Jun 18;6(26):22496–22512 (Goldenberg).
Regarding claims 1, 4, 10, 12-14, 16 and 18, WO 480 discloses anti-TROP-2 antibody-drug conjugates for cancer treatment:
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See pages 17+.
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record.
Namely, unlike pre-AIA law, the AIA provides that a foreign priority date can be the effective filing date of a claimed invention. The foreign priority date is the effective filing date of the claimed invention IF
-the foreign application supports the claimed invention under 112(a), AND
-the applicant has perfected the right of priority by providing:
a certified copy of the priority application, and
a translation of the priority application (if not in English).
When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate.
The primary references may not explicitly teach conjugates with anti-TROP-2 antibodies. However, the secondary references demonstrate that Trop-2 is a transmembrane glycoprotein overexpressed in many solid tumors (e.g., breast, lung, urothelial), making it an ideal target for antibody-drug conjugates. It is for that proposition that the rejection joins the secondary references.
See Starodub (“Sacituzumab govitecan (IMMU-132) is a novel ADC comprising SN-38, the active metabolite of the topoisomerase inhibitor, irinotecan, conjugated to an anti-Trop-2 humanized antibody. Its uniquely very high drug:antibody ratio of 7.6 allows delivering up to 136-fold more SN-38 than its parent drug, irinotecan, in a human cancer xenograft. The mAb and ADC are immunotherapeutic in vitro (ADCC). Expression of Trop-2 is increased in most epithelial cancers (>80%), including SCLC.”).
See Goldenberg (“Trop-2 is a novel target for ADC therapy because of its high expression by many solid cancers… A novel target in multiple solid cancers for an ADC is trophoblast cell-surface antigen, or Trop-2, also known as tumor-associated calcium signal transducer (TACSTD2), epithelial glycoprotein-1 (EGP-1), gastrointestinal tumor-associated antigen (GA733-1), and surface marker 1 (M1S1)”).
In this way, those of ordinary skill could have applied the recited anti-TROP-2-antibodies in the manner required and in a predictable fashion for the purposes of providing the instant ADC’s. As outlined above, the primary references teach that ADC’s with the core linker-drugs were known. The secondary references are added for the proposition that the recited targeting antibodies, i.e., anti-TROP-2, are applicable to these ADC’s. Specifically, the secondary references teach that the particular known technique of using anti-TROP-2 antibodies in ADC’s was recognized as part of the ordinary capabilities of one skilled in the art. In this manner those of ordinary skill would have recognized that applying the known technique to ADC’s, such as those taught by the primary references, would have yielded predictable results. Accordingly, using the recited anti-TROP-2 antibodies for the purposes of preparing the instant ADC’s would have been prima facie obvious.
Claims 2, 5, 7, 8 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over:
WO 2020063673 and counterparts;
CN 111689980;
WO 2020244657 and counterparts;
WO 2021115426 and counterparts;
WO 2021121204 and counterparts; or
WO 2021190480 (WO 480)
in view of: Starodub et al., Abstract, J Clin Oncol 34, 8559(2016) (Starodub) and Goldenberg et al., Oncotarget. 2015 Jun 18;6(26):22496–22512 (Goldenberg);
in further view of: WO 2021148003 and counterpart U.S. Publication No. US 20230144203 to Huang et al (collectively “Huang”).
Regarding claims 2, 5, 7, 8 and 19, the primary and secondary references may fail to explicitly teach the particular anti-TROP-2 antibody. However, this antibody and its use in ADC’s was known, as evidenced by Huang, see page 20 (SEQ ID’s HC, LC, CDR’s) of the U.S. Publication. In this manner, those of ordinary skill would have recognized that applying the known antibody to ADC’s, such as those taught by the primary references, would have yielded predictable results. Accordingly, using the recited anti-TROP-2 antibodies for the purposes of preparing the instant ADC’s would have been prima facie obvious.
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, 2, 4, 5, 7, 8, 10, 12-14, 16, 18, 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. 12377163 in view of Starodub, Goldenberg and Huang.
Although the claims at issue are not identical, they are not patentably distinct from each other since the rejected claims cover linker-drug constructs that anticipate those covered by the rejected claims. Alternatively, the difference between the rejected claims and the conflicting claims is that the conflicting claims do recite the instant conjugates and methods with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the claimed conjugates with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
Specifically, Starodub Goldenberg and Huang demonstrate that ADC’s with the recite anti-TROP-2 antibody were within the purview of those of ordinary skill, and thus, prima facie obvious, as outlined above.
Claims 1, 2, 4, 5, 7, 8, 10, 12-14, 16, 18, 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 45-57 of U.S. Application No. 17596239 in view of Starodub, Goldenberg and Huang.
Although the claims at issue are not identical, they are not patentably distinct from each other since the rejected claims cover linker-drug constructs that anticipate those covered by the rejected claims. Alternatively, the difference between the rejected claims and the conflicting claims is that the conflicting claims do recite the instant conjugates and methods with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the claimed conjugates with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
Specifically, Starodub, Goldenberg and Huang demonstrate that ADC’s with the recite anti-TROP-2 antibody were within the purview of those of ordinary skill, and thus, prima facie obvious, as outlined above.
Claims 1, 2, 4, 5, 7, 8, 10, 12-14, 16, 18, 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Application No. 17782980 in view of Starodub, Goldenberg and Huang.
Although the claims at issue are not identical, they are not patentably distinct from each other since the rejected claims cover linker-drug constructs that anticipate those covered by the rejected claims. Alternatively, the difference between the rejected claims and the conflicting claims is that the conflicting claims do recite the instant conjugates and methods with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the claimed conjugates with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
Specifically, Starodub, Goldenberg and Huang demonstrate that ADC’s with the recite anti-TROP-2 antibody were within the purview of those of ordinary skill, and thus, prima facie obvious, as outlined above.
Claims 1, 2, 4, 5, 7, 8, 10, 12-14, 16, 18, 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-20, 22-25 of U.S. Application No. 17785373 in view of Starodub, Goldenberg and Huang.
Although the claims at issue are not identical, they are not patentably distinct from each other since the rejected claims cover linker-drug constructs that anticipate those covered by the rejected claims. Alternatively, the difference between the rejected claims and the conflicting claims is that the conflicting claims do recite the instant conjugates and methods with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the claimed conjugates with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
Specifically, Starodub Goldenberg and Huang demonstrate that ADC’s with the recite anti-TROP-2 antibody were within the purview of those of ordinary skill, and thus, prima facie obvious, as outlined above.
Claims 1, 2, 4, 5, 7, 8, 10, 12-14, 16, 18, 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Application No. 17914087 in view of Starodub, Goldenberg and Huang.
Although the claims at issue are not identical, they are not patentably distinct from each other since the rejected claims cover linker-drug constructs that anticipate those covered by the rejected claims. Alternatively, the difference between the rejected claims and the conflicting claims is that the conflicting claims do recite the instant conjugates and methods with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the claimed conjugates with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
Specifically, Starodub and Goldenberg demonstrate that ADC’s with the recite anti-TROP-2 antibody were within the purview of those of ordinary skill, and thus, prima facie obvious, as outlined above.
Claims 1, 2, 4, 5, 7, 8, 10, 12-14, 16, 18, 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16, 18-20 of U.S. Application No. 17914209 in view of Starodub, Goldenberg and Huang.
Although the claims at issue are not identical, they are not patentably distinct from each other since the rejected claims cover linker-drug constructs that anticipate those covered by the rejected claims. Alternatively, the difference between the rejected claims and the conflicting claims is that the conflicting claims do recite the instant conjugates and methods with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the claimed conjugates with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
Specifically, Starodub and Goldenberg demonstrate that ADC’s with the recite anti-TROP-2 antibody were within the purview of those of ordinary skill, and thus, prima facie obvious, as outlined above.
Claims 1, 2, 4, 5, 7, 8, 10, 12-14, 16, 18, 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Application No. 17913928 in view of Starodub, Goldenberg and Huang.
Although the claims at issue are not identical, they are not patentably distinct from each other since the rejected claims cover linker-drug constructs that anticipate those covered by the rejected claims. Alternatively, the difference between the rejected claims and the conflicting claims is that the conflicting claims do recite the instant conjugates and methods with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the claimed conjugates with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
Specifically, Starodub, Goldenberg and Huang demonstrate that ADC’s with the recite anti-TROP-2 antibody were within the purview of those of ordinary skill, and thus, prima facie obvious, as outlined above.
Claims 1, 2, 4, 5, 7, 8, 10, 12-14, 16, 18, 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13 and 14 of U.S. Application No. 18032086 in view of Starodub, Goldenberg and Huang.
Although the claims at issue are not identical, they are not patentably distinct from each other since the rejected claims cover linker-drug constructs that anticipate those covered by the rejected claims. Alternatively, the difference between the rejected claims and the conflicting claims is that the conflicting claims do recite the instant conjugates and methods with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the claimed conjugates with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
Specifically, Starodub, Goldenberg and Huang demonstrate that ADC’s with the recite anti-TROP-2 antibody were within the purview of those of ordinary skill, and thus, prima facie obvious, as outlined above.
Conclusion
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646