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
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.
This application contains polypeptide and/or polynucleotide sequences. Applicant is required to review the Specification for sequence compliance, as outlined above.
Specification
The Specification is objected to. Specifically, a trade name or a mark used in commerce, has been noted in this application, e.g., Lipofectamine, page 35; Pierce, page 53. 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 Objections
Claims 1-35 are objected to because of the following informalities:
The antibody name is obscured:
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Appropriate correction is required.
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 12, 15-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating cancer, does not reasonably provide enablement for any other diseases such as those associated with undesired angiogenesis. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
“The standard for determining whether the specification meets the enablement requirement [in accordance with the statute] was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term "undue experimentation," it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988). See also United States v. Telectronics, Inc., 857 F.2d 778, 785, 8 USPQ2d 1217, 1223 (Fed. Cir. 1988) ("The test of enablement is whether one reasonably skilled in the art could make or use the invention from the disclosures in the patent coupled with information known in the art without undue experimentation."). A patent need not teach, and preferably omits, what is well known in the art. In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991); Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1384, 231 USPQ 81, 94 (Fed. Cir. 1986), cert. denied, 480 U.S. 947 (1987); and Lindemann Maschinenfabrik GMBH v. American Hoist & Derrick Co., 730 F.2d 1452, 1463, 221 USPQ 481, 489 (Fed. Cir. 1984). Determining enablement is a question of law based on underlying factual findings. In re Vaeck, 947 F.2d 488, 495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991); Atlas Powder Co. v. E.I. du Pont de Nemours & Co., 750 F.2d 1569, 1576, 224 USPQ 409, 413 (Fed. Cir. 1984).” See M.P.E.P. § 2164.
Here, the nature of the invention is diagnosing and treating cancer with a chelated radioisotope antibody conjugate targeted for the urokinase plasminogen activator receptor (uPA). In this regard, determining the pharmacological profile of a particular antibody-drug conjugate is not routine and the level of ordinary skill in the art of treating cancer is high, as an ordinary artisan in this art needs specialized knowledge of the complex nature of cancer and antibody-drug conjugate chemistry. Applicant is reminded of the heightened enablement for these types of inventions: Specifically, the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. [I]n the field of chemistry generally, there may be times when the well-known unpredictability of chemical reactions will alone be enough to create a reasonable doubt as to the accuracy of a particular broad statement put forward as enabling support for a claim. This will especially be the case where the statement is, on its face, contrary to generally accepted scientific principles. Most often, additional factors, such as the teachings in pertinent references, will be available to substantiate any doubts that the asserted scope of objective enablement is in fact commensurate with the scope of protection sought and to support any demands based thereon for proof. [Footnote omitted.].
Therefore, either the state of the art or the specification needs to establish that Cdc42 inhibitors can treat diseases associated with angiogenesis.
The prior art teaches that diseases characterized by excessive or abnormal angiogenesis (new blood vessel formation) include cancers (feeding tumor growth), diabetic retinopathy, age-related macular degeneration, rheumatoid arthritis, psoriasis, atherosclerosis, obesity, and conditions involving chronic inflammation or ischemia like Crohn's disease, see:
Jensen et al., Chin Med J (Engl). 2025 Apr 21;138(10):1153–1162 (“Sustained inflammation leads to the expression of angiogenic factors by the recruited inflammatory cells, thereby inducing angiogenesis[48] and increasing tissue perfusion…sustained hypoxia and inflammation are present in and drive pathological progression in most common diseases including: (1) rheumatoid or other chronic inflammatory disorders,[48,49] (2) metabolic disorders including obesity and late-stage diabetes,[50,51] (3) cardiovascular disorders including plaque growth and destabilization, ischemic stroke, or myocardial infarction,[52] (4) respiratory disorders such as chronic obstructive lung disease and coronavirus disease 2019,[53,54] (5) eye diseases including age-related macular degeneration, diabetic retinopathy, and retinopathy of pre-maturity,[55] and (6) most types of cancer and premalignant diseases.[56] Under these pathological conditions, angiogenesis is uncontrolled, leading to ectopic vessels with poor stability, maturity, and function being constantly formed and broken down without anastomosing with other vessels. Therefore, these vessels are leaky, leading to the accumulation of interstitial fluid, which compresses the mature vessels and reduces tissue perfusion[57] [Figure 1]. These pathological vasculatures lead to sustained hypoxia and inflammation, creating a vicious cycle that drives disease progression.”)
La Mendola et al., Int J Mol Sci. 2022 Sep 19;23(18):10962 (“Angiogenesis is a multi-step process by which new blood capillaries are formed starting from preexisting functional vessels [1]. Angiogenesis is strictly regulated by the balance of many positive and negative angiogenic modulators within the vascular microenvironment [2]…There is accumulating evidence that many diseases are angiogenesis-dependent. Pathological angiogenesis is a hallmark of many cancers, diabetic retinopathy, autoimmune diseases, rheumatoid arthritis, atherosclerosis, cerebral ischemia, cardiovascular diseases and delayed wound healing [3,4].”)
Dudley et al., Angiogenesis. 2023 Apr 15;26(3):313–347 (“Different mechanisms such as vasculogenesis, sprouting, intussusceptive, and coalescent angiogenesis, as well as vessel co-option, vasculogenic mimicry and lymphangiogenesis, underlie the formation of new vasculature. In many pathological conditions, such as cancer, atherosclerosis, arthritis, psoriasis, endometriosis, obesity and SARS-CoV-2(COVID-19), developmental angiogenic processes are recapitulated, but are often done so without the normal feedback mechanisms that regulate the ordinary spatial and temporal patterns of blood vessel formation. Thus, pathological angiogenesis presents new challenges yet new opportunities for the design of vascular-directed therapies. Here, we provide an overview of recent insights into blood vessel development and highlight novel therapeutic strategies that promote or inhibit the process of angiogenesis to stabilize, reverse, or even halt disease progression. In our review, we will also explore several additional aspects (the angiogenic switch, hypoxia, angiocrine signals, endothelial plasticity, vessel normalization, and endothelial cell anergy) that operate in parallel to canonical angiogenesis mechanisms and speculate how these processes may also be targeted with anti-angiogenic or vascular-directed therapies.”).
However, the use of chelated radioisotope antibody conjugates targeted for uPA are limited to for cancer treatment and metastasis, see Background section of the Specification:
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Therefore, the use of these conjugates for treatment and diagnosis of cancer may be characterized as “known”, but use of such conjugates to treat other diseases is not predictable. For instance, there is no nexus between the use of these conjugates and other diseases associated with angiogenesis. Thus, it is unpredictable whether a conjugate used for cancer treatment can also be used to treat other diseases associated with angiogenesis, since there doesn’t appear to be a link between cancer treatment in general and treatment of other diseases covered by the claims that are characterized by unwanted angiogenesis, such as diabetic retinopathy, age-related macular degeneration, rheumatoid arthritis, psoriasis, atherosclerosis, obesity, and conditions involving chronic inflammation or ischemia like Crohn's disease.
The specification fails to remedy the state of the art. Here the specification shows activity of the instant conjugates against cancer cells. Therefore, a nexus may be established between the experimental results and the treatment of cancer. The specification does not provide any additional examples or guidance on how to use the recited conjugates to treat any other diseases. Thus, the specification provides sufficient teachings only for the enablement of treatment of cancers. The prior art provides no compensatory guidance and it would require undue experimentation to practice the invention for treating other diseases. The amount of experimentation would be undue because it would require determining how to use the conjugates to treat diseases besides cancer, such as those associated with angiogenesis. Specifically, as outlined above, it is not routine to determine how an antibody conjugate will act on a complex biochemistry to treat different conditions. In the instant case, it is only known that the instant conjugates have cytotoxic activity against uPA receptor-positive cancer cells. This means that significant experimentation would be required to determine how the conjugates can be used to treat other diseases not associated with the uPA receptor. Those of ordinary skill in the art cannot extrapolate between the anti-cancer activity of the conjugates and the pharmacology of other diseases. Moreover, there is little guidance, in both the prior art and the specification, with respect to the use of such conjugates to treat diseases other than cancer.
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 1-35 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 term “the chemically-bonded monoclonal IgG1 kappa light chain subgroup 2 (VK2) type antibody” in claims 1 and 35 lacks antecedent basis.
The term “the VK2 variable region (VL)” in claim 35 lacks antecedent basis.
The term “the kappa chain 00 region (LC)” in claim 35 lacks antecedent basis.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Janet Epps-Smith, can be reached at telephone number (571)272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646