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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/24/2023, 09/15/2023, and 04/08/2024 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
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 1-10 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.
With regard to claims 1-10, Applicant claims the use of and incorporation of ARMS2 or an active fragment thereof into a pharmaceutical composition. Applicant has not, however, disclosed any embodiments of the ARMS2 protein in a fragment form. Rather, Applicant has disclosed the full form of the protein via SEQ ID NO: 1. Given that Applicant has not demonstrated the possession or use of a functional or active fragment of the protein, a person having ordinary skill in the art would not know that Applicant has possession of a representative sample of embodiments of the claimed scope of proteins. More specifically, given that only certain fragments of proteins may retain the desired function in the instant application, it would not be obvious to one having ordinary skill in the art which fragments maintain this function. As such, without disclosure or evidence of experimentation to arrive at said fragments, Applicant has not fulfilled the requirements of written description for the active fragments. It is advised that Applicant revise the claims to encompass only the embodiments that fulfill written description in the specification.
Claims 1-10 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 making and using the ARMS2 protein, does not reasonably provide enablement for making and using active fragments thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. See Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
With regard to the breadth of the claims, the nature of the invention, and the level of unpredictability in the art, Applicant claims in claims 1-10 the use and incorporation of an active fragment of ARMS2, which includes any fragment of any length and amino acid composition derived from ARMS2 that can be considered functional. Here, the breadth of the claim is broad, and the nature of the invention as a peptide necessarily implies that only certain fragments will retain the function of the peptide as a whole. Given that Applicant has not disclosed any fragments in the specification, a person having ordinary skill in the art would not necessarily know which fragments retain the desired function, particularly considering that the functionality of protein fragments is unpredictable. Here, Apostolopoulos et al. teach that modeling of the peptides is challenging the size and flexibility of peptides are prohibitive for exact calculations, and full understanding of the peptides requires further progress on both modelling and thermodynamic aspects of their interactions (see pages 14 and 15, paragraphs 2 and 1, respectively). Further, Apostolopoulos et al. discuss some of the challenges of using short peptides peptide fragments as opposed to entire proteins, and these challenges include lack of receptor selectivity, short half-life in vivo, low binding affinity, and more (see Table 1). Similarly, with regard to the amount of direction given by Applicant and the existence of working examples, Applicant does not disclose working examples or fragments or direction for making and using fragments, as discussed above. Without direction for active fragments of the protein, a person having ordinary skill in the art would not reasonably be able to model functional portions of the protein without significant and undue experimentation.
Similarly, with regard to the level of ordinary skill in the art, state of the prior art, and the quantity of experimentation needed to make or use the invention based on the content of the disclosure, a person having ordinary skill in the art would not be able to predict which protein fragments would maintain the active function of ARMS2. As discussed above, Apostolopoulos et al. teach that modeling of the peptides is challenging the size and flexibility of peptides are prohibitive for exact calculations, and full understanding of the peptides requires further progress on both modelling and thermodynamic aspects of their interactions (see pages 14 and 15, paragraphs 2 and 1, respectively). As such, significant and undue experimentation would be required to arrive at active fragments, as it is a difficult and unpredictable process.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Honisch et al. (as noted on the IDS filed 04/08/2024, Honisch et al., "ARMS2 Particularly Interacts With Modulators of ECM Affecting Migration Behavior of Human RPE Cells", Investigative Ophthalmology & Visual Science, Vol. 60, 4894. doi, July 2019, 2 pages), as evidenced by Apostolopoulos et al. (Apostolopoulos, Vasso et al. “A Global Review on Short Peptides: Frontiers and Perspectives.” Molecules (Basel, Switzerland) vol. 26,2 430. 15 Jan. 2021) and Hart et al. (Hart, S L et al. “Integrin-mediated transfection with peptides containing arginine-glycine-aspartic acid domains.” Gene therapy vol. 4,11 (1997): 1225-30).
With regard to claim 1, Honisch et al. teach ARMS2 overexpression leads to a significant increase in migration (26% ± 6.7%; p=0.034) and invasion (20% ± 4.8%, p=0.012) of retinal pigmented epithelium cells, and that is it involved in wound healing (see Abstract). They found that the abundance of ECM remodeling proteins like TIMP1, MMP2 and MMP14 was highly upregulated while cell viability remained unaffected (see Abstract). The pull-down assay identified significant enriched ARMS2 binding partners known to be involved in ECM remodeling and cell migration like Collagen Type VI Alpha (COL6A3), Coactosin-Like 1 (COTL1), Desmoglein (DG1), Dystroglycan (DAG1) and Fibrinogen gamma (FGG) (see Abstract). They found that these results confirm the function of ARMS2 as a modulator of extracellular matrix homeostasis and cell migration (see Abstract). Here, ARM2 was overexpressed in living cells of the human eye, hTert-RPE1, and was assessed for its role in wound healing. Honisch et al. do not teach the administration of ARMS2 to a living subject. Apostolopoulos et al. do, however, teach a motivation for integrating peptides investigated via highly expressed cell membrane forms into therapeutic applications for treating disease in patients (see page 18, paragraph 1). Specifically, Apostolopoulos et al. teach that key cancer gene therapies have been investigated utilizing highly expressed integrin proteins that are important factors in short peptide treatments (see page 18, paragraph 1). Here, Apostolopoulos et al. provide a clear motivation to try to administer to a patient proteins or protein ligands that show desirable experimental results, particularly those related to integrins, which are closely functionally related to the ECM. As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date to try to administer the ARMS2 protein to a living being.
With regard to claim 2, Honisch et al. teach the use of human eye cells, hTert-RPE1, and human eye cells inherently and implicitly express human ARMS2 (see Abstract).
With regard to claim 3, Honisch et al. teach that the ARMS2 binds ECM proteins (see Abstract), but they do not teach the use of an active fragment of the protein. Apostolopoulos et al. teach that the use of short peptides or peptide fragments as opposed to the entire protein is beneficial in pharmaceuticals because they can significantly reduce production costs (see page 8, paragraph 2). Given this motivation to use an active fragment of the peptide, it would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to use an active fragment.
With regard to claim 4, Honisch et al. teach that the ARMS2 binds ECM proteins, but they do not explicitly teach that it binds Fibulin-6, Fibronectin-1, and EMILIN2. Seeing as Honisch et al. and the instant application both teach ARMS2, the structures of the proteins are the same, meaning that the functions are necessarily and inherently the same. More specifically, relevant case law has established that "products of identical chemical composition can not have mutually exclusive properties" In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. As such, the ARMS2 taught by Henisch et al. is capable of binding the intended targets of the instant application. As discussed above, Apostolopoulos et al. provide a clear motivation for using active fragments of peptides as opposed to the whole protein, and, given the reasoning above, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references.
With regard to claim 5, Honisch et al. teach the use of ARMS2 in wound healing, but they do not explicitly teach that the ARMS2 heals skin wounds. Regardless, given that Honisch et al. claim the same protein, ARMS2, it inherently has the same structure and function as the ARMS2 claimed in the instant application. As discussed above, a chemical composition and its properties are inseparable, and therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. As such, the ARMS2 of Honisch et al. is inherently capable of healing wounds of the skin.
With regard to claim 6, Honisch et al. teach the use of ARMS2 in wound healing, but they do not explicitly teach that the ARMS2 closes blood vessels. Regardless, given that Honisch et al. claim the same protein, ARMS2, it inherently has the same structure and function as the ARMS2 claimed in the instant application. As discussed above, a chemical composition and its properties are inseparable, and therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. As such, the ARMS2 of Honisch et al. is inherently capable of blood vessel closure.
With regard to claim 7, Honisch et al. teach the use of ARMS2 in wound healing, but they do not explicitly teach that the ARMS2 promotes wound closure. Regardless, given that Honisch et al. claim the same protein, ARMS2, it inherently has the same structure and function as the ARMS2 claimed in the instant application. As discussed above, a chemical composition and its properties are inseparable, and therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. As such, the ARMS2 of Honisch et al. is inherently capable of promoting wound closure.
With regard to claim 8, Honisch et al. teach the use of ARMS2 in wound healing, but they do not explicitly teach that the ARMS2 promotes scar formation. Regardless, given that Honisch et al. claim the same protein, ARMS2, it inherently has the same structure and function as the ARMS2 claimed in the instant application. As discussed above, a chemical composition and its properties are inseparable, and therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. As such, the ARMS2 of Honisch et al. is inherently capable of promoting scar formation.
With regard to claim 9, as discussed above, Honisch et al. teach ARMS2 overexpression leads to a significant increase in migration (26% ± 6.7%; p=0.034) and invasion (20% ± 4.8%, p=0.012) of retinal pigmented epithelium cells, and that is it involved in wound healing (see Abstract). They found that the abundance of ECM remodeling proteins like TIMP1, MMP2 and MMP14 was highly upregulated while cell viability remained unaffected (see Abstract). The pull-down assay identified significant enriched ARMS2 binding partners known to be involved in ECM remodeling and cell migration like Collagen Type VI Alpha (COL6A3), Coactosin-Like 1 (COTL1), Desmoglein (DG1), Dystroglycan (DAG1) and Fibrinogen gamma (FGG) (see Abstract). They find that these results confirm the function of ARMS2 as a modulator of extracellular matrix homeostasis and cell migration (see Abstract). Here, ARM2 was overexpressed in living cells of the human eye, hTert-RPE1, and was assessed for its role in wound healing. Honisch et al. do not teach the administration of ARMS2 to a living being. Apostolopoulos et al. do, however, teach a motivation for integrating highly expressed proteins into therapeutic applications for treating disease in patients (see page 18, paragraph 1). Specifically, Apostolopoulos et al. teach that human cancer gene therapies have been investigated utilizing highly expressed human integrin proteins, αvβ3 integrins, (see Hart et al. page 1229, paragraph 5) that are key factors in short peptide treatments (see Apostolopoulos et al. page 18, paragraph 1). Here, Apostolopoulos et al. provide a clear motivation to try to administer to a human patient proteins or protein ligands that show desirable experimental results, particularly those related to integrins, which are closely functionally related to the ECM. As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date to try to administer the ARMS2 protein to a human subject.
With regard to claim 10, Honisch et al. teach the overexpression of ARMS2 in human eye cells to assess its role in wound healing through its interactions with ECM proteins. Honisch et al. do not, however, teach a pharmaceutical composition for promoting wound healing comprising an age-related maculopathy susceptibility protein 2 (ARMS2) or an active fragment thereof, or a nucleic acid molecule encoding said ARMS2 or said active fragment thereof, or an expression vector comprising said nucleic acid molecule, and a pharmaceutically acceptable carrier. As discussed above, Apostolopoulos et al. teach a motivation for integrating peptides investigated via highly expressed cell membrane forms into therapeutic applications for treating disease in patients (see page 18, paragraph 1). Specifically, Apostolopoulos et al. teach that cancer gene therapies have been investigated utilizing highly expressed integrin proteins that are key factors in short peptide treatments (see page 18, paragraph 1). Here, Apostolopoulos et al. provide a clear motivation to try to administer to a patient proteins or protein ligands that show desirable experimental results, particularly integrins, which are closely functionally related to the ECM. Apostolopoulos et al. also provide motivations for specific forms of pharmaceutical compositions, including compositions comprising pharmaceutically acceptable carriers and nanocarriers, which achieve desired benefits including controlled release (see page 8, paragraph 2) and increased drug delivery with high biocompatibility, low toxicity, and high stability (see page 9, paragraph 3). As discussed above, Apostolopoulos et al. also teach that the use of short peptides or active peptide fragments as opposed to the entire protein is beneficial in pharmaceuticals because they can significantly reduce production costs (see page 8, paragraph 2). Here, Apostolopoulos et al. provide clear motivations for the use of proteins/peptides or active fragments thereof in pharmaceutical compositions with pharmaceutically acceptable carriers. As such, it would have been obvious to one having ordinary skill in the art prior to the effective filing date of the instant application to combine the references to make and use a pharmaceutical composition comprising the ARMS2 protein or an active fragment thereof with a pharmaceutically acceptable carrier.
Summary
Claims 1-10 are rejected on the grounds of obviousness under 35 U.S.C. 103. Claims 1-10 are rejected under 35 U.S.C. 112(a) on the grounds of scope of enablement and written description.
Conclusion
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/BRENDAN P. OLISS/Examiner, Art Unit 1658
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654