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 .
The Applicants’ Amendment to the Claims filed on 08/19/2026 is entered.
Claims 1-10 are cancelled.
Claims 11-30 are pending.
Claims 11, and 18-23 are withdrawn.
Claims 12-17, and 24-30 are under examination.
This is the First Office Action on the Merits of US 18/573,587 filed on 12/22/2023 which is a 371 of PCT/US2023/029733 filed on 08/08/2023 which claims US priority benefit of US Provisional Applications 63/526,786 filed 07/14/2023, 63/523,970 filed 06/29/2023, 63/472,674 filed 06/13/2023, 63/459,762 filed 04/17/2023, 63/458,471 filed on 04/11/2023, 63/447,371 filed on 02/22/2023, filed on 63/444,451 filed on 02/09/2023, 63/431,946 filed on 12/12/2022 and 63/396,040 filed on 08/08/2022.
Election/Restrictions
Applicant's election with traverse of invention Group II (e.g., claims 12-17, and 24-30) in the reply filed on 08/19/2026 is acknowledged. The traversal is on the ground(s) that the applicants argue that the Vaillant reference does not establish a composition comprising a cross-linking molecule and a small molecule modulator targeted to a porosome protein. The applicants argue that “At most, the cited Vaillant disclosure concerns inhibition of specified HBV/HDV-related targets, including microtubule-actin crosslinking factor. Applicants argue that it does not disclose “a porosome-targeted modulator”. This is not found persuasive because to break unity the reference is not required to anticipate the present claims. Rather, claims lack unity because the groups lack the same or corresponding special technical feature of a composition comprising a cross-linking molecule and a small molecule modulator targeted to a porosome protein. The Vaillant reference shows that the technical feature of a composition comprising a cross-linking molecule and a small molecule modulator targeted to a porosome protein does not make a contribution over the prior art in view of Vaillant et al. Actin is a type of porosome protein.
The requirement is still deemed proper and is therefore made FINAL.
Claims 11, and 18-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention Group, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 08/19/2026.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/396,040 filed on 08/08/2022, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The ‘040 Provisional has an eleven page Specification whereas the instant application has Specification. The ‘040 Provisional does not support the subject matter of any of present claims 12-17, and 24-30. For example, the ‘040 Provisional does not recite the term porosome or the genus of small molecule modulators targeted to a porosome protein. The ‘040 Provisional does not disclose a humanized nanobody that binds a domain of a porosome protein. The ‘040 Provisional does not disclose the element of artificial cysteine.
Information Disclosure Statement
The IDS statements filed on 05/26/2026, 02/06/2026, 08/22/2025, 04/02/2025, 07/31/2024, and 12/22/2023.
Claim Objections
Claim 12 is objected to because of the following informalities: Claim 1 is missing a term such as “and” or “or” after the phrase “at least one cross-linking molecule”. For purpose of examination, consistent with the specification, the claim is construed to intend an “and”. Appropriate correction is required.
Claims 13 and 15 are objection to because claim 13 recites the abbreviated term “ELP” and claim 15 recites the abbreviated term “pAcF”. These terms should be written in full-length the first time they appear in the claims.
Claim 30 is objected to for reciting an “i” step twice (rather than an i & j step).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 28 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 28 fails to include all the limitations of claim 14 upon which it depends. Claim 28 is drawn to the humanized nanobody of claim 14. However, claim 14 is drawn to a composition comprising such nanobody. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Written Description
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.
Claims 12-17, 24, and 26-30 are rejected under 35 U.S.C. 112(a) 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.
Claims 12-16, 24, and 26-30 are drawn to a composition comprising a small molecule capable of binding one or more porosome proteins. In addition, claims 14, 15-17, and 28-30 are drawn to a composition comprising: a nanobody engineered to bind to one or more domains of one or more porosome proteins.
Thus, claims 12-16, 24, and 26-30 require the critically essential element of a genus of small molecules capable of binding one or more porosome proteins. Also, claims 14, 15-17, and 28-30 require the critically essential element of a genus of nanobodies engineered to bind to one or more domains of one or more porosome protein.
However, the specification does not provide a representative set of species of such small molecules or nanobody structures correlated to the required binding functions to fulfill the requirements of written description with regard to the broad genus of small molecules or nanobodies encompassed the claims.
Regarding the genus of small molecules, the specification disclose the small molecule species of doxorubicin and CDN1163 (small molecule stimulator of Calcium transporting ATPase (CTA). Thus, claim 25 is not included in this rejection. Claim 17 is included in this rejection because although doxorubicin is a known species of small molecule, claim 17 depends from claims 15-16 an claim 16 recite a nanobody. Also, the specification discloses a sub-genus of small molecules that bind/target some specific porosome proteins. See instant Table 5 showing a representative set of small molecules drugs for targeting microtubules which contain the porosome protein tubulin beta. Also, Table 5 shows several more sub-genuses of small molecules that bind/target a sub-group of 16 different types of porosome proteins. For example, Table 5 shows a sub-genus for small molecule inhibitors of myosin 7b. However, the instant Specification discloses a vast number of porosome proteins without providing a subset of small molecules targeting such. For example, Table 1 shows 28 types of porosome proteins. Table 6 shows 34 type of porosome proteins.
In addition, regarding the genus of nanobodies, the specification provides no nanobody structures but rather refers to nanobodies as engineered against one or more domains of one or more porosome proteins (see para 0122-0123). For example, the specification contemplates embodiments of certain nanobodies engineered to attach t-SNARE or v-SNARE but show no structure of such nanobodies. (See para 0091). However, the specification does not provide a representative set of such functional species of nanobodies to represent the vast genus of nanobodies encompassed by the claims as presently written.
Further, the state of the art before the effective filing date of the presently claimed invention shows that the correlation of nanobody structure to their function was unpredictable. According to Hacisuleyman et al ("ModiBodies: A computational method for modifying nanobodies to improve their antigen binding and specificity," bioRxiv, October 2019), therapeutic nanobodies, are highly specific and require precise targets to attach to (see Abstract).
One of ordinary skill in the art cannot predict the structure of a functional small molecule or of a functional nanobody by defining the porosome protein or antigen to which it binds. Rather, the structure of the small molecule or nanobody must be envisioned to satisfy the written description requirement. Adequate written description requires more than a mere statement that a compound is part of the invention and reference to a potential method of isolating a compound. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
As such, Applicant has not fulfilled the requirements of written description with regard to the broad genus of nanobodies.
Written Description – reach-thru claim
Claim 30 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claim 30 depends from claim 15 which is drawn to a product composition. The composition comprises a humanized nanobody with a small molecule and an artificial cysteine. The claimed product does not require a porosome protein but requires that the small molecule is capable of binding a porosome protein. Claim 30 is drawn to a screening method to identify the porosome protein of claim 15. Please see MPEP 2163: Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, para. 1, “Written Description” Requirement”, which states that the “claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function”. The MPEP 2163 II. A. 3.(a)(i) recites that “for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession”.
In the instant case, a skilled artisan at the time the application was filed would not have recognized that the inventor was in possession of the invention as claimed because the nature of the invention is drawn to products which are discovered by performing the screening assay of claim 30. Although the applicant shows possession of the methods of claim 30, and possession of the art-recognized general formula of porosome proteins such as the compounds represented claim 29, they do not appear to show possession of the broad genus of products comprising any small molecules capable of binding to a porosome obtained by performing the screening methods according to claim 30.
Such "reach-through" claims were addressed by the Federal Circuit in University of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886 (Fed. Cir. 2004). See M.P.E.P. § 2163.
Regarding the written description requirement in reach-through situations, the CAFC wrote, "While it is true that this court and its predecessor have repeatedly held that claimed subject matter 'need not be described in haec verba' in the specification to satisfy the written description requirement…it is also true that the requirement must still be met in some way so as to 'describe the claimed invention so that one skilled in the art can recognize what is claimed.' Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 963 at 968 (63 USPQ2d 1609) (Fed. Cir. 2002). We have further explained that: [T]he appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. … A description of an anti-inflammatory steroid, i.e., a steroid (a generic structural term) described even in terms of its function of lessening inflammation of tissues fails to distinguish any steroid from others having the same activity or function. A description of what a material does, rather than of what it is, usually does not suffice. [Regents of the Univ. of Cal. v.] Eli Lilly [& Co., Inc.], 119 F.3d [1559,] 1568 [43 USPQ2d 1398] [(Fed. Cir. 1997) ("Lilly")] …
The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. Id. Enzo, 323 F.3d at 968. Similarly, for example, in the nineteenth century, use of the word "automobile" would not have sufficed to describe a newly invented automobile; an inventor would need to describe what an automobile is, viz., a chassis, an engine, seats, wheels on axles, etc. Thus, generalized language may not suffice if it does not convey the detailed identity of an invention." Rochester, 358 F.3d at 1892.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 12 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sumitha et al in “Degradation-Dependent Controlled Delivery of Doxorubicin by Glyoxal Cross-Linked Magnetic and Porous Chitosan Microspheres” ACS Omega, published August 9, 2021).
Regarding base claim 12, Sumitha et al discloses a composition, comprising:
a glyoxal which is a cross-linking molecule; and,
the small molecule doxorubicin which is defined by instant claim 17 as a small molecule capable of binding a porosome protein. See Abstract; Scheme 1).
Thus Sumitha et al anticipates claim 12.
Claims 12-17, 24, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Costa et al in “Active Targeting of Cancer Cells by Nanobody Decorated Polypeptide Micelle with Bio-orthogonally Conjugated Drug” (Nano Lett, 2019 Vol 19, pages 247-254; IDS ref & Attached Supporting Material for Costa et al 2019).
Regarding base claims 12 and 15, Costa et al disclose a composition comprising a humanized nanobody conjugated to doxorubicin and comprising an artificial cysteine where the cysteine is bound to an ELP diblock and the ELP deblock is bound to a cross-linking molecule pAcf. See entire article and Graphical Abstract just below:
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Regarding claim 13, Costa et al disclose the cross-linking molecule is an ELP deblock.
Regarding claim 14, Costa et al disclose that the nanobody binds a porosome protein which is doxorubicin. (See Fig 1 just below).
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Regarding claim 16, Costa et al disclose that the doxorubicin is attached to the pAcF. (See Fig 1 above).
Regarding claim 17, Costa et al disclose that the doxorubicin is attached to the pAcF. (See Fig 1 above).
Regarding claim 24, Costa et al disclose the cross-linking molecule p-acetyl phenylalanine (pAcf). (See Fig 1 above).
Regarding claim 30, because this claim is a reach-thru claim as discussed above, the process recited in the claim is not afforded patentable weight for purpose of applying prior art. Claim 30 drawn to the composition of claim 15 and is anticipated for the same reasons applied to claim 15.
Thus, Costa et al anticipate claims 12-17, 24, and 30.
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.
Claims 12, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Sumitha et al in “Degradation-Dependent Controlled Delivery of Doxorubicin by Glyoxal Cross-Linked Magnetic and Porous Chitosan Microspheres” ACS Omega, published August 9, 2021), in view of Qaisar et al in “Restoration of SERCA ATPase prevents oxidative stress-related muscle atrophy and weakness” (Redox Biology Vol 20, pages 68-74, available online 09/27/2018).
Claim 12 is anticipated by Sumitha et al for reasons provided above. Sumitha et al disclose a composition, comprising: a glyoxal which is a cross-linking molecule; and the therapeutic small molecule doxorubicin which is a small molecule capable of binding a porosome protein. (See above).
Regarding claim 25, Sumitha et al disclose the composition comprising the small molecule doxorubicin but do not disclose the small molecule CDN1163.
Regarding claim 25, Qaisar et al discloses a composition comprising the small molecule CDN1163 capable of targeting the porosome protein called SERCA (Sarcoplasmic Reticulum Ca2+ ATPase). Qaisar et al showed that CDN1163 is a small molecule allosteric SERCA activator, which ameliorated muscle impairment in a mouse model for muscle weakness and atrophy. (See Abstract). Qaisar et al suggest that “the pharmacological restoration of SERCA is a promising therapeutic approach to counter oxidative stress-associated muscle impairment” (see Abstract).
The level of skill in the art was high before the effective filing date of the presently claimed invention.
One of ordinary skill in the art would have been motivated to include the therapeutic small molecule CDN1163 into a micellar nanoparticle delivery system comprising the cross-linking molecule glyoxal of Sumitra et al for the rationale of providing a drug delivery system for pharmacological restoration of SERCA to treat muscle impairment.
In view of the high skill level in the art it is considered that one of ordinary skill in the art having the cited references before the effective filing date of the presently claimed invention would have had a reasonable expectation of success to compose a composition comprising the small molecule drug delivery system of Sumitra et al with the CDN1163 small molecule of Qaisar et al to arrive at the presently claimed invention.
Claims 12, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Dai et al in “Refining the Design of Diblock Elastin-Like Polypeptides for Self-Assembly into Nanoparticle” (Polymers 2021, Vol 13, published May 1, 2021), in view of Qaisar et al in “Restoration of SERCA ATPase prevents oxidative stress-related muscle atrophy and weakness” (Redox Biology Vol 20, pages 68-74, available online 09/27/2018).
Regarding claims 12-13, Dai et al disclose a composition comprising thermoresponsive polymers for drug delivery systems. Dai et al disclose the use of the cross-linking molecule which is an ELP deblock for making such thermoresponsive polymers. Dai et al disclose the incorporation of an artificial cysteine which is bound to the ELP deblock.
Dai et al differs from instant claim 12 because it does not explicitly disclose a drug payload being a small molecule capable of binding a porosome protein.
Qaisar et al discloses a composition comprising the small molecule CDN1163 capable of targeting the porosome protein called SERCA (Sarcoplasmic Reticulum Ca2+ ATPase). Qaisar et al showed that CDN1163 is a small molecule allosteric SERCA activator, which ameliorated muscle impairment in a mouse model for muscle weakness and atrophy. (See Abstract). Qaisar et al suggest that “the pharmacological restoration of SERCA is a promising therapeutic approach to counter oxidative stress-associated muscle impairment” (see Abstract).
The level of skill in the art was high before the effective filing date of the presently claimed invention.
One of ordinary skill in the art would have been motivated to include the therapeutic small molecule CDN1163 into a micellar nanoparticle delivery system comprising the cross-linking molecule ELP deblock of Dai et al for the rationale of providing a drug delivery system for pharmacological restoration of SERCA to treat muscle impairment.
In view of the high skill level in the art it is considered that one of ordinary skill in the art having the cited references before the effective filing date of the presently claimed invention would have had a reasonable expectation of success to compose a composition comprising the drug delivery system of Dai et al with the CDN1163 small molecule of Qaisar et al to arrive at the presently claimed invention.
Conclusion
No claim is allowed.
Related prior art which may be applied in a future office action if appropriate:
Schwiebert et al PNAS Vol 89, pages 10623-10627, 1992; IDS ref). Schwiebert et al disclose a disease-related porosome protein.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658
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