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 .
Summary
Claims 1-20 are pending in this office action. All pending claims are under examination in this application.
Priority
The current application was filed on May 21, 2024 claims domestic priority to provisional patent application 63/504,385 filed on May 25, 2023.
Information Disclosure Statement
Receipt of the Information Disclosure Statements filed on July 31, 2024 and October 2, 2024 are acknowledged. A signed copy of both documents are attached to this office action.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because Figures 4 and 5 are blurry and the text is not readable. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
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.
Claims 1-3, 5, 8, 14, 16, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al. (Bioactive Materials, 2021).
Wu et al. is considered the closest prior art to the claimed invention as it teaches injectable and thermosensitive hydrogels mediating a universal macromolecular contrast agent with radiopacity for noninvasive imaging of deep tissues (see title). Furthermore, Wu et al. disclose that it is very challenging to visualize implantable medical devices made of biodegradable polymers in deep tissues. Herein, we designed a novel macromolecular contrast agent with ultrahigh radiopacity (iodinate content> 50%) via polymerizing an iodinated trimethylene carbonate monomer into the two ends of poly(ethylene glycol) (PEG). A set of thermosensitive and biodegradable polyester-PEG-polyester triblock copolymers with varied polyester compositions synthesized by us, which were soluble in water at room temperature and could spontaneously form hydrogels at body temperature, were selected as the demonstration materials. The addition of macromolecular contrast agent did not obviously compromise the injectability and thermogelation properties of polymeric hydrogels, but conferred them with excellent X-ray opacity, enabling visualization of the hydrogels at clinically relevant depths through X-ray fluoroscopy or Micro-CT. In a mouse model, the 3D morphology of the radiopaque hydrogels after injection into different target sites was visible using Micro-CT imaging, and their injection volume could be accurately obtained. Furthermore, the subcutaneous degradation process of a radiopaque hydrogel could be non-invasively monitored in a real-time and quantitative manner. In particular, the corrected degradation curve based on Micro-CT imaging well matched with the degradation profile of virgin polymer hydrogel determined by the gravimetric method. These findings indicate that the macromolecular contrast agent has good universality for the construction of various radiopaque polymer hydrogels, and can nondestructively trace and quantify their degradation in vivo. Meanwhile, the present methodology developed by us affords a platform technology for deep tissue imaging of polymeric materials (see abstract).
Regarding instant claim 1, Wu et al. teach a radiopaque, reactive copolymer. The necessary citations within Wu et al. that pertain to instant claim 1 are presented in Table I.
Table I
Instant Claim 1
Wu et al. Citations
A radiopaque, reactive copolymer comprising
Wu et al. (see Figure 1 and Figure 2A) disclose the radiopaque, reactive triblock polycarbonate-PEG-polycarbonate copolymer PITMC-PEG-PITMC.
at least one hydrophilic polymer segment having a plurality of hydrophilic polymer segment ends,
This polymer contains one hydrophilic PEG segment that is linked to iodinated polycarbonate polymer segments (PITMC) with both ends. The PITMC segments are covalvently linked to reactive primary hydroxy groups.
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200
400
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(see Figure 1).
Wu et al. (see Figure 1) further disclose that the monomer used for the preparation of the PITMC segments of the polymer is the cyclic carbonate ester 5,5-Bis- (iodomethyl)-1,3-dioxan-2-one.
Wu et al. (see Figure 3A; page 4720, left-hand column, paragraph 1 - right-hand column, paragraph 1) disclose a system for forming a hydrogel composition that comprises the reactive, radiopaque copolymer and a polyester-PEG-polyester copolymer (P1, P2 or P3). These polymers (see Figure 1 and Figure S4) are prepared from glycolide, lactide and/or caprolactone monomers and are nucleophilic compounds as they comprise primary hydroxy end groups.
a plurality of iodinated polymer segments covalently linked to the plurality of hydrophilic polymer segment ends,
and a plurality of reactive moieties covalently linked to the iodinated polymer segments.
Regarding instant claims 2-3, 5, 8, 14, 16, and 18, Wu et al. teach the appropriate instant claim limitations.
Please see the discussion and citations within instant claim 1 for the necessary rejection text.
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 non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 4, 6-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. in view of Alexis et al. (US2015/0290344A1).
[The Examiner is going to introduce the new reference and then combine them where appropriate to reject the instant claims.]
1. Alexis et al.
Alexis et al. teach biodegradable polyester-and poly(esteramide) based X-ray imaging agents (see title). Additionally, Alexis et al. disclose biodegradable, radio-opaque polyesters and poly(esteramides) are described herein. The polyesters contain a plurality of radio-opaque agents or radio-opaque agent-containing moieties that are covalently bound along or from the polymer backbone. The agents/moieties may be bound to the termini of the polymer provided they are bound within the polyester backbone as well. The polyester can be aliphatic or aromatic. The polyester and poly(ester amide) is substituted with a plurality of radio-opaque graft agents or prepared from an appropriate radio-opaque monomer agent. The materials can be used for any application where a radio-opaque material is desired or necessary. The materials can be used to form, in whole or in part, a medical device, or coating thereon or therein (see abstract).
The teachings of Wu et al. are discussed within the 35 U.S.C. §102 Section above.
Ascertaining the Difference
The teachings of Wu et al. alone do not encompass the remaining instant claim limitations. Alexis et al. compliments Wu et al. and expands on the radio-opaque agents that can be used by a skilled artisan. Therefore, the combination of Wu et al. and Alexis et al. is employed for rejection purposes.
Combination of Wu et al. and Alexis et al.
Regarding instant claim 4, Wu et al. and Alexis et al. teach wherein the at least one hydrophilic polymer segment comprises a plurality of hydrophilic polymer segments and wherein the radiopaque, reactive copolymer comprises a plurality of polymer arms linked to a core region, the polymer arms each comprising one of the plurality hydrophilic polymer segments, one of the plurality of iodinated polymer segments, and one of the plurality of reactive moieties.
Alexis et al. disclose linear, branched and starshaped radiopaque polyesters comprising a plurality of radiopaque agents covalently bound to the polymer that are prepared by ring-opening polymerization of glycolide, lactide and caprolactone. In some embodiments, the polyester is crosslinked with small molecules or mixed with PEG as a second co-polymer (see paragraphs [0009]-[0011] and [0013] within Alexis et al.). Alternatively, the skilled person would attach the ITMC monomer of Wu et al. to the star-shaped PEG polymer of Alexis et al. instead of the linear PEG of Wu et al. in the course of routine experimentation.
Regarding instant claims 6 and 7, Wu et al. and Alexis et al. teach wherein the reactive moiety comprises an electrophilic group.
The skilled person would transform the terminal hydroxy groups of the reactive polymer of Wu et al. to carboxylates or other reactive groups common in the art [e.g. NHS (N-hydroxysuccinimide) esters] for bioconjugation using common general knowledge without inventive skill.
Regarding instant claim 9, Wu et al. and Alexis et al. teach wherein the iodinated cyclic ester monomer is selected from an iodinated lactone and an iodinated 1,4-dioxane-2,5-dione compound.
Alexis et al. disclose the preparation of the monomer 3-[(4-iodophenyl)methyl]-6-methyl-1,4-dioxane-2,5-dione ("4-iodobenzyl lactide") and the polyester thereof (see Example 8; claims 21 and 22; both within Alexis et al.).
Regarding instant claims 10, 12, and 13, Wu et al. and Alexis et al. teach wherein the plurality of iodinated polymer segments is iodinated polyester segments in which at least one iodinated moiety is covalently attached to a polyester backbone of the iodinated polyester segments.
The skilled person would replace the ITMC monomer of Wu et al. with 4-iodobenzyl lactide of Alexis et al. or a related compound in the course of routine experimentation to prepare a radio-opaque, reactive copolymer. By doing so, the skilled person would arrive at the subject matter of the desired instant claims without exercising inventive skill (see also paragraphs [0070-0071] within Alexis et al.).
Regarding instant claim 11, Wu et al. and Alexis et al. teach wherein the iodinated moiety comprises a monocyclic or multicyclic aromatic structure that is substituted with one or more iodine groups.
Alexis et al. disclose wherein the iodinated moiety comprises a monocyclic or multicyclic aromatic structure that is substituted with one or more iodine groups (see paragraphs [0070-0071] within Alexis et al.).
Regarding instant claim 15, Wu et al. and Alexis et al. teach wherein the nucleophilic compound is a polyamino compound.
Alexis et al. disclose star-shaped PEG polymers with various nucleophilic and electrophilic end groups. The polyamino compound, Poly-L-lysine, is mentioned as crosslinker (see paragraphs [0082]-[0083] within Alexis et al.).
Regarding instant claim 17, Wu et al. and Alexis et al. teach further comprising an accelerant composition.
A skilled artisan (POSITA; person of ordinary skill in the art) using both the Wu et al. and Alexis et al. disclosures as a guide, could incorporate an accelerant composition into the synthetic organic chemistry transformation of choice (basic buffering composition).
Regarding instant claim 19, Wu et al. and Alexis et al. teach a radiopaque crosslinked hydrogel composition comprising a crosslinked reaction product of (a) a nucleophilic compound and (b) a radiopaque, reactive copolymer in accordance with instant claim 6.
Please see the discussion and citations within instant claims 1, 6, and 7 for the necessary rejection text.
Regarding instant claim 20, Wu et al. and Alexis et al. teach a method of treatment comprising administering to a subject a mixture that comprises (a) a nucleophilic compound and (b) radiopaque, reactive copolymer comprising at least one hydrophilic polymer segment having a plurality of hydrophilic polymer segment ends, a plurality of iodinated polymer segments covalently linked to the plurality of hydrophilic polymer segment ends, and a plurality of reactive moieties covalently linked to the iodinated polymer segments, under conditions such that the nucleophilic compound and the radiopaque, reactive copolymer crosslink after administration.
Please see the discussion and citations within instant claim 1 for the necessary rejection text. Additionally, Alexis et al. disclose cross-linking can occur after administration using enzymes, thermal, and UV/gamma irradiation (see paragraph [0088] within Alexis et al.). [Wu et al. disclose the hydrogel formation under body temperature (thermal) conditions (see abstract within Wu et al.).]
Analogous Art
The Wu et al. and Alexis et al. references are directed to the same field of endeavor as the instant claims, that is, a radiopaque, reactive copolymer, as disclosed within instant claim 1.
Obviousness Analysis
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the radiopaque, reactive copolymer disclosed by Wu et al., using the teachings of Alexis et al. in order to arrive at the subject matter of the instant claims.
The Wu et al. and Alexis et al. references all have considerable overlap in the radiopaque arts. In this instance, Wu et al. supplies the radiopaque, reactive copolymer template, while Alexis et al. expands the radiopaque, reactive copolymers to diversify the polymeric analogues. Both references are directed to radiopaque, reactive copolymers and therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the two references when seeking to develop radiopaque, reactive copolymers for medical applications.
Given these teachings, a POSITA would have been motivated to combine the radiopaque, reactive copolymer as disclosed by Wu et al., and the synthetic variations disclosed by Alexis et al.
The modification constitutes a simple substitution of one known element for another to obtain a predictable result [MPEP §2143(I)(B)].
The combination represents the use of a known technique to improve a similar composition in the same way [MPEP §2143(I)(C)].
The art provides a finite number of identified, predictable solutions, and the POSITA would have pursued the claimed configuration with a reasonable expectation of success [MPEP §2143(I)(E); KSR].
The combination of the radiopaque, reactive copolymer taught by Wu et al. along with the use of the necessary claim limitations taught by Alexis et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application.
Furthermore, the additional claim limitations taught by Alexis et al. would have been viewed by a POSITA as routine design optimizations or known modifications within radiopaque, reactive copolymers. The motivation for doing so would have been to incorporate alternative and expansive synthetic modifications within the radiopaque, reactive copolymer series, with the goal being to identify the most attractive pre-clinical candidate. Implementing these features in Wu et al.’s radiopaque, reactive copolymer would not require more than ordinary skill or routine experimentation.
Accordingly, the combination of Wu et al. and Alexis et al. provides all the elements of the claimed invention. The resulting radiopaque, reactive copolymers, constitute no more than the predictable outcome of combining familiar prior art components, and therefore the claimed subject matter would have been obvious to a POSITA prior to the effective filing date of the invention.
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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, 5, 11, 14-18, and 20 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1, 3, 5, and 15-20 of co-pending Application No. 19/205,442 (reference application) in view of Alexis et al.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and that of Application ‘442 encompass radiopaque, reactive polymers.
The difference between the instant claims and that of Application ‘442 is the use of iodinated amino-acid residues within the radiopaque, reactive polymers.
However, Alexis et al. teach biodegradable polyester-and poly(esteramide) based X-ray imaging agents (see title). Additionally, Alexis et al. disclose biodegradable, radio-opaque polyesters and poly(esteramides) are described herein. The polyesters contain a plurality of radio-opaque agents or radio-opaque agent-containing moieties that are covalently bound along or from the polymer backbone. The agents/moieties may be bound to the termini of the polymer provided they are bound within the polyester backbone as well. The polyester can be aliphatic or aromatic. The polyester and poly(ester amide) is substituted with a plurality of radio-opaque graft agents or prepared from an appropriate radio-opaque monomer agent. The materials can be used for any application where a radio-opaque material is desired or necessary. The materials can be used to form, in whole or in part, a medical device, or coating thereon or therein (see abstract).
It would have been prima facie obvious to use iodinated amino acids (see paragraphs [0056-0057] and [0071] within Alexis et al.) as suggested by Alexis et al. Despite the fact that iodinated amino acids are not fully disclosed within Alexis et al., the cited paragraphs above give ample evidence to a skilled artisan (POSITA) to pursue this halogenated material. There would have been a reasonable expectation of success in doing so as both Alexis et al. and Application ‘442 are radiopaque, reactive polymers.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 5, 11, 14-18, and 20 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1, 3, 5, and 15-20 of co-pending Application No. 19/367,065 (reference application) in view of Alexis et al.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and that of Application ‘065 encompass radiopaque, reactive polymers.
The difference between the instant claims and that of Application ‘065 is the use of iodinated amino-alcohol residues within the radiopaque, reactive polymers.
However, Alexis et al. teach biodegradable polyester-and poly(esteramide) based X-ray imaging agents (see title). Additionally, Alexis et al. disclose biodegradable, radio-opaque polyesters and poly(esteramides) are described herein. The polyesters contain a plurality of radio-opaque agents or radio-opaque agent-containing moieties that are covalently bound along or from the polymer backbone. The agents/moieties may be bound to the termini of the polymer provided they are bound within the polyester backbone as well. The polyester can be aliphatic or aromatic. The polyester and poly(ester amide) is substituted with a plurality of radio-opaque graft agents or prepared from an appropriate radio-opaque monomer agent. The materials can be used for any application where a radio-opaque material is desired or necessary. The materials can be used to form, in whole or in part, a medical device, or coating thereon or therein (see abstract).
It would have been prima facie obvious to use iodinated amino alcohols (see paragraphs [0057] and [0071] within Alexis et al.) as suggested by Alexis et al. Despite the fact that iodinated amino acids are not fully disclosed within Alexis et al., the cited paragraphs above give ample evidence to a skilled artisan (POSITA) to pursue this halogenated material. There would have been a reasonable expectation of success in doing so as both Alexis et al. and Application ‘065 are radiopaque, reactive polymers.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN W LIPPERT III whose telephone number is (571)270-0862. The examiner can normally be reached Monday - Thursday 9:00 AM - 5:00 PM.
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/JOHN W LIPPERT III/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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