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 statement filed October 22, 2024 is acknowledged by the examiner.
The information disclosure statement filed October 22, 2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. In this instance, the Benjamin, E. J.; et al., Circulation, 2017 non-patent literature publication has not been provided. The IDS has been placed in the application file, but that particular reference has not been considered.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because of the following informalities:
Paragraph [0004] states that the application contains at least one drawing executed in color. However, no color drawings have been provided to the examiner nor is there a petition to include color drawings. If the lack of color drawings is intentional, this paragraph should be removed.
In the chemical structure within paragraph [000135], the superscript “18” is at poor resolution and is insufficiently legible.
In reaction scheme 6 of paragraph [000144], the “18F” on the last reaction arrow and in the final product structure are at poor resolution and is insufficiently legible.
In the recitation of Structure I within paragraphs [000153], [000161], [000165], and [000172]; the superscript “18” is at poor resolution and is insufficiently legible.
In reaction scheme 1 of paragraph [000174], the “18F” on the last reaction arrow and in the final product structure are at poor resolution and is insufficiently legible.
Appropriate correction is required.
Claim Objections
Claims 1, 5, 6, 9, 11, and 13 are objected to because of the following informalities:
In claims 1, 9, and 13, the superscript “18” in each recitation of Structure I is at poor resolution and is insufficiently legible.
Claims 5 and 11 recite ”99Tc”. In view of the disclosure as a whole, it appears what is meant is “99mTc”.
In claim 6, the second line starts with the word “liposoma.” In view of the claim as a whole, it appears what is meant is “liposomal.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-16 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.
Claims 1, 9, and 13 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: in Structure III, the HO-(CH2CH2O)q-H option for moiety Z is a complete structure. There are no open valences in this recited structural option. Therefore, it is not clear how this polyethylene glycol group can be attached to the nitrogen of Structure 3 where group Z is depicted. It is unclear whether the point of attachment is to a terminal oxygen (requiring the removal of one of the recited hydrogens) or to a central carbon or oxygen of the repeating unit (also requiring the removal of a hydrogen from these atoms). Furthermore, if the attachment point is to the end of the PEG group, it is unclear if it is meant that a bond is formed between the PEG oxygen and the omecamtiv mecarbil core nitrogen (forming an O-N bond) or if the nitrogen is to replace the terminal oxygen of the PEG chain, resulting in an alkyl modified nitrogen connected to a PEG chain. It is also unclear if it is meant that a linker moiety is permitted to exist between the nitrogen and the PEG group. For these reasons, the examiner considers there to be a lack of essential structural relationship described for this structural option for Z, rendering the claimed structure (and thus the claim as a whole) indefinite in scope). Furthermore, as claims 2-8, 10-12, and 14-16 depend from claims 1, 9, and 13, respectively, and do not further specify the Z group to resolve the indefiniteness, these claims are also rejected. For the purpose of examination, the examiner will interpret any means of attaching a PEG group having 2-2,000 repeat units at this position to read on this embodiment of Structure III.
Claims 1 and 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: the attachment point of the linker molecule on the omecamtiv mecarbil compound or omecamtiv mecarbil analog or derivative (of Structures I, II, and III). The examiner notes that Structures I, II, and III as recited are complete structures with no open valencies. This is also true for omecamtiv mecarbil itself. The examiner also interprets the scope of the targeting vectors as described in claims 1 and 13 to require the linking of the head group to the anchoring group by a linker molecule that covalently bonds each of the head and anchoring groups. However, as the structures to be modified with the linker are complete structures, the introduction of a new covalent bond would likely require the substitution of a hydrogen from one of the carbon or nitrogen atoms or the removal of a portion of the molecule to reveal a reactive attachment point. There is no available attachment point for a linker molecule depicted on any of omecamtiv mecarbil or Structures I, II, and III. Therefore, it is not clear where or how a linker molecule is to be attached to these structures. As it is unclear where the attachment point is or if such attachment allows for the substitution of hydrogens or other atoms in the recited structures, the examiner considers there to be an omission of essential structural relationships amounting to a gap between components. Therefore, claims 1 and 13 are rendered indefinite. Furthermore, as claims 2-8 and 14-16 depend from claims 1 and 13, respectively, and these claims do not resolve the structural omission, these claims are also rejected. For the purpose of examination, the examiner will consider the attachment of a linker molecule to any part of the omecamtiv mecarbil molecule or analog or derivative thereof with the allowance of substitution of hydrogens or other portions of the claimed structures to read on this limitation.
Claim 6 recites the limitation "the anchoring/stabilizing moiety" in line 2. There is insufficient antecedent basis for this limitation in the claim. The term “stabilizing” is not otherwise used in claim 6 or claim 1 (upon which claim 6 depends). For the purpose of examination, the examiner will interpret this phrase to refer to the “anchoring/solubilizing moiety” as recited in claim 1.
Claim 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: the attachment point of the cargo molecule on the omecamtiv mecarbil analogs or derivatives of Structures I, II, and III. The examiner notes that Structures I, II, and III as recited are complete structures with no open valencies. The examiner also interprets “linked” in claim 10 to require covalent attachment of the cargo molecule to the omecamtiv mecarbil analog or derivative. However, as Structures I, II, and III depict complete structures, the introduction of a new covalent bond would likely require the substitution of a hydrogen from one of the carbon or nitrogen atoms or the removal of a portion of the molecule to reveal a reactive attachment point. There is no available attachment point for a cargo molecule depicted on any of Structures I, II, and III. Therefore, it is not clear where or how a cargo molecule is to be attached to these structures. As it is unclear where the attachment point is or if such attachment allows for the substitution of hydrogens or other atoms in the recited structures, the examiner considers there to be an omission of essential structural relationships amounting to a gap between components. Therefore, claim 10 is rendered indefinite. For the purpose of examination, the examiner will consider the attachment of a cargo molecule to any part of the omecamtiv mecarbil analog or derivative structures with the allowance of substitution of hydrogens or other portions of the claimed structures to read on this claim.
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.
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.
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 and 2 are rejected under 35 U.S.C. 103 as being unpatentable over Biswas (Biswas, S.; et al., Bioconjug. Chem., 2011) in view of Malik (Malik, F. I.; et al., Science, 2011 – provided by applicant in IDS filed October 22, 2024).
Biswas teaches liposomes for targeted delivery of therapeutics (pg. 2005, Abstract). More specifically, Biswas teaches preparing liposomes with egg phosphatidyl choline, cholesterol, and antibody-linked PEG-DSPE (pg. 2007, left column, paragraphs 2 and 3). The Antibodies are conjugated to the DSPE phospholipid via modifications to the end of the PEG linker wherein a hydrazine-modified PEG reacts with an aldehyde modified antibody (pg. 2006, last paragraph; Figure 1; pg. 2007, left column, paragraphs 1-3). Biswas teaches that the liposomes can be prepared using a 2G4 monoclonal antibody (pg. 2007, left column, paragraph 3), which is specific for cardiac myosin (pg. 2006, right column, first paragraph). Biswas teaches that the 2G4-modified liposomes bind to cardiac myosin in vitro (pg. 2010, Figure 4b). Biswas teaches that liposomes can be used as drug delivery systems (pg. 2005, Introduction, paragraph 1).
Biswas does not teach a cardiac myosin targeting vector comprising a head group that comprises omecamtiv mecarbil or an analog thereof.
Malik teaches the direct activator of cardiac myosin omecamtiv mecarbil (pg. 1439, Abstract; and pg. 1440, Figure 1A). Malik teaches that omecamtiv mecarbil directly binds to cardiac myosin S1 protein (pg. 1441, Figure 2). Malik teaches that omecamtiv mecarbil increases cardiac myocyte contractility while not changing the calcium homeostasis (pg. 1441, Figure 3). Malik suggests that cardiac myosin activation by omecamtiv mecarbil may provide a therapeutic approach for systolic heart failure (pg. 1439, Abstract).
A person of ordinary skill in the art would have recognized that both the 2G4 antibody of Biswas and the omecamtiv mecarbil molecule of Malik are molecules that selectively bind to cardiac myosin protein. It would also be recognized that Malik teaches that omecamtiv mecarbil binding to myosin has favorable pharmacological effects such as increased cardiomyocyte contractility.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the targeted liposome of Biswas by substituting the myosin-targeting antibody with the omecamtiv mecarbil molecule of Malik because these are both cardiac myosin binding molecules that would serve the same purpose in a liposome, enabling targeting to myocardial tissue (MPEP § 2143(I)(B)) and because the omecamtiv mecarbil would impart its own pharmacological effect upon binding to myosin, adding treatment properties to the liposome (MPEP § 2143(I)(C)). This would predictably result in a liposome comprising a cardiac myosin targeting vector comprising omecamtiv mecarbil, a linker, and a lipid anchoring moiety.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this substitution because a practitioner in targeted liposomes is capable of using and performing various reactions to conjugate targeting moieties to linker and lipid groups, such as the hydrazone linkage taught by Biswas.
The skilled artisan would have been motivated to make this modification because using a small molecule instead of antibody allows for more dense decoration of the liposome with targeting groups, giving more binding sites per liposome for myosin, which can result in improved target binding parameters. Additionally, Malik teaches that omecamtiv mecarbil binding to cardiac myosin produces positive pharmacological effects in the context of heart failure. Incorporation of this property in a liposome would increase the therapeutic potential of the targeted liposome.
Regarding claim 1, Biswas teaches a liposome comprising DSPE-PEG-2G4 (pg. 2007, Figure 1; left column, paragraph 3) and teaches that 2G4 is a cardiac myosin specific antibody (pg. 2006, right column, paragraph 1). Biswas describes the PEG group as a linker in the conjugate structure (pg. 2011, left column, paragraph 1). Biswas depicts the lipid component of the DSPE-PEG-2G4 conjugate as incorporating into the lipid bilayer of the liposome (pg. 2005, Abstract Figure). Therefore, the examiner interprets DSPE to be a lipid anchoring/solubilizing moiety. Additionally, Malik teaches omecamtiv mecarbil (pg. 1440, Figure 1A) and teaches that omecamtiv mecarbil specifically binds cardiac myosin S1 (pg. 1441, Figure 2). For the reasons provided above, it would have been prima facie obvious to substitute the 2G4 antibody of Biswas for the omecamtiv mecarbil of Malik. The resulting product would be a liposome containing DSPE-PEG-omecamtiv mecarbil. This component can be described as having a head group of omecamtiv mecarbil, a PEG linker, and a DSPE lipid anchoring/solubilizing moiety. Therefore, the combined teachings of Biswas and Malik render claim 1 obvious.
Regarding claim 2, Biswas teaches a liposome containing a cardiac myosin targeting vector wherein the linker molecule comprises polyethylene glycol (pg. 2005, Abstract Figure; Figure 1; pg. 2007, left column, paragraphs 2 and 3). Therefore, the combined teachings of Biswas and Malik render claim 2 obvious.
Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over Biswas and Malik as applied to claims 1 and 2 above, and further in view of Senior (Senior, R.; et al., Am. Heart J., 1993).
As described above, Biswas teaches liposomes for targeted delivery of therapeutics comprising antibody-linked PEG-DSPE (pg. 2007, left column, paragraphs 2 and 3). Biswas teaches that the liposomes can be prepared using a 2G4 monoclonal antibody (pg. 2007, left column, paragraph 3), which is specific for cardiac myosin (pg. 2006, right column, first paragraph). Biswas teaches that liposomes can be used as drug delivery systems (pg. 2005, Introduction, paragraph 1). Additionally, Malik teaches the direct activator of cardiac myosin omecamtiv mecarbil (pg. 1439, Abstract; and pg. 1440, Figure 1A). Malik teaches that omecamtiv mecarbil directly binds to cardiac myosin S1 protein (pg. 1441, Figure 2). Malik teaches that omecamtiv mecarbil increases cardiac myocyte contractility while not changing the calcium homeostasis (pg. 1441, Figure 3). As described above, the combined teachings of Biswas and Malik teach a liposome comprising a cardiac myosin targeting vector containing an omecamtiv mecarbil head group conjugated to a DSPE lipid anchoring/solubilizing moiety by a PEG linker molecule.
The combined teachings of Biswas and Malik do not teach a cardiac myosin targeting vector comprising a cargo linked thereto.
Senior teaches the use of 99mTc labeled antimyosin antibodies for imaging (pg. 536, Abstract). More specifically, Senior teaches labeling an antimyosin antibody with 99mTc directly or by conjugation of an RP-1 chelator to the antibody and subsequently complexing 99mTc in the chelator (pg. 537, Isotope Labeling). Senior teaches using the 99mTc labeled antimyosin antibodies to image myocardial infarction (pg. 537, Antimyosin Imaging; pg. 538, Antimyosin Antibody Imaging; pg. 539, Figures 1 and 2). Senior teaches that 99mTc labeled antimyosin antibody is an effective diagnostic tool for early imaging of myocardial infarction (pg. 541, last paragraph).
A person of ordinary skill in the art would have recognized that both the 2G4 antibody of Biswas and the antibody of Senior are anti-myosin antibodies. It would also be recognized that the 2G4 antibody of Biswas, the antibody of Senior, and the omecamtiv mecarbil molecule of Malik are molecules that selectively bind to cardiac myosin protein. It would be recognized that Senior teaches that a myosin binding molecule can be labeled with 99mTc to enable its use in cardiac imaging.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the liposomes containing a DSPE-PEG-omecamtiv mecarbil cardiac myosin targeting vector taught by the combination of Biswas and Malik by modifying the targeting vector with a 99mTc label as taught by Senior because this modification would enable the imaging of the liposomes in biological systems and cardiac tissue in the same way the label was used by Senior with respect to the antimyosin antibody (MPEP § 2143(I)(C)). This would predictably result in a liposome comprising a cardiac myosin targeting vector comprising omecamtiv mecarbil, a linker, and a lipid anchoring moiety labeled with 99mTc for imaging applications.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this modification because a practitioner in radionuclide labeling is capable of using and performing various reactions to conjugate chelating moieties to targeting molecules, such as the RP-1 chelator attachment taught by Senior. As omecamtiv mecarbil and the DSPE-PEG groups contain various functional groups, standard chemistry methods could be used to use or create reactive handles for conjugation of a chelator to the targeting vector.
The skilled artisan would have been motivated to make this modification because Senior teaches that the 99mTc radiolabel enables the use of the molecule for imaging applications. This would enable imaging of the distribution of the targeted liposome in the body, ensuring the liposome or associated drug delivery reaches desired locations.
Regarding claim 3, as described above, the combined teachings of Biswas and Malik teach a liposome comprising a cardiac myosin targeting vector containing an omecamtiv mecarbil head group conjugated to a DSPE lipid anchoring/solubilizing moiety by a PEG linker molecule, rendering claim 1 obvious. Additionally, Senior teaches radiolabeling a myosin binding/targeting molecule with 99mTc (pg. 537, Isotope Labeling). One method of Senior involves the ligation of an RP-1 chelator to the myosin targeting molecule followed by coordination of the 99mTc radionuclide (pg. 537, Isotope Labeling). As described above, it would have been prima facie obvious to apply the labeling methods of Senior to the cardiac myosin targeting vector and liposome taught by the combination of Biswas and Malik. The resulting combination would produce a chelator-conjugated cardiac myosin targeting vector coordinated to 99mTc. The examiner interprets the radionuclide coordinated chelating group to be a cargo molecule linked to the targeting vector. Therefore, the combined teachings of Biswas, Malik, and Senior render claim 3 obvious.
Regarding claim 4, Senior teaches using the 99mTc labeled antimyosin antibodies to image myocardial infarction (pg. 537, Antimyosin Imaging; pg. 538, Antimyosin Antibody Imaging; pg. 539, Figures 1 and 2). Therefore, the examiner interprets the 99mTc radionuclide bound chelating group to be an imaging agent. Therefore, the combined teachings of Biswas, Malik, and Senior render claim 4 obvious.
Regarding claim 5, as described above, the combined teachings of Biswas and Malik teach a liposome comprising a cardiac myosin targeting vector containing an omecamtiv mecarbil head group conjugated to a DSPE lipid anchoring/solubilizing moiety by a PEG linker molecule, rendering claim 1 obvious. Additionally, Senior teaches radiolabeling a myosin binding/targeting molecule with 99mTc (pg. 537, Isotope Labeling). Senior teaches direct labeling with 99mTc and indirect labeling through ligation of an RP-1 chelator to the myosin targeting molecule followed by coordination of the 99mTc radionuclide (pg. 537, Isotope Labeling). As described above, it would have been prima facie obvious to apply the labeling methods of Senior to the cardiac myosin targeting vector and liposome taught by the combination of Biswas and Malik. The resulting combination would produce a 99mTc complexed or conjugated cardiac myosin targeting vector. Therefore, the combined teachings of Biswas, Malik, and Senior render claim 5 obvious.
Claims 6-8, 13, 15, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Biswas and Malik as applied to claims 1 and 2 above, and further in view of Dasa (Dasa, S. S. K.; et al., J. Controlled Release, 2015).
As described above, Biswas teaches liposomes for targeted delivery of therapeutics comprising antibody-linked PEG-DSPE (pg. 2007, left column, paragraphs 2 and 3). Biswas teaches that the liposomes can be prepared using a 2G4 monoclonal antibody (pg. 2007, left column, paragraph 3), which is specific for cardiac myosin (pg. 2006, right column, first paragraph). Biswas teaches that liposomes can be used as drug delivery systems (pg. 2005, Introduction, paragraph 1). Additionally, Malik teaches the direct activator of cardiac myosin omecamtiv mecarbil (pg. 1439, Abstract; and pg. 1440, Figure 1A). Malik teaches that omecamtiv mecarbil directly binds to cardiac myosin S1 protein (pg. 1441, Figure 2). Malik teaches that omecamtiv mecarbil increases cardiac myocyte contractility while not changing the calcium homeostasis (pg. 1441, Figure 3). As described above, the combined teachings of Biswas and Malik teach a liposome comprising a cardiac myosin targeting vector containing an omecamtiv mecarbil head group conjugated to a DSPE lipid anchoring/solubilizing moiety by a PEG linker molecule.
The combined teachings of Biswas and Malik do not teach a cardiac myosin targeting vector disposed in a cargo-loaded liposome. The combined teachings of Biswas and Malik also do not teach the use of a cardiac myosin targeting vector in combination with a cardiac-treating drug in a method of treating a cardiac condition.
Dasa teaches drug-loaded targeted liposomes for the treatment of myocardial infarction (pg. 556, Abstract). More specifically, Dasa teaches liposomes comprising DSPE-PEG conjugated to peptides through a thiol-maleimide linkage (pg. 558-559, Section 2.2.8). The liposomes also comprise phosphocholines (pg. 559, Section 2.2.8). The peptides were prepared by in vivo phage display of post-myocardial infarction tissue (pg. 560, Figure 1; pg. 557-558, Section 2.2.2). Dasa teaches selecting phage clone peptides specific to identifying markers of cells types of interest in myocardial tissue (pg. 561, Figure 2). Dasa also teaches loading the myocardial targeting liposomes with AZ7379 (pg. 559, Section 2.2.9), which is a PARP-1 inhibitor (pg. 557, left column, paragraph 2). Dasa teaches that the targeted liposomes accumulate in myocardial tissue in a post-MI heart (pg. 563, Figure 4). Dasa teaches that the liposomes can effectively be loaded with AZ7379 and that they display controlled release (pg. 564, Figure 5). Dasa teaches that the AZ7379 loaded liposomes can be used to reduce PARP-1 function in cardiomyocytes (pg. 565, Figure 6). Dasa suggests using such a drug loaded liposome to deliver cell type specific therapeutic molecules to improve cardiac function following a myocardial infarction (pg. 565, left column, paragraph 1).
A person of ordinary skill in the art would have recognized that both the DSPE-PEG-omecamtiv mecarbil containing liposomes of the combination of Biswas and Malik and the DSPE-PEG-peptide liposomes of Dasa are cardiac tissue targeting liposomes that could be used for drug delivery. It would also be recognized that these liposomes are similar in composition. It would be recognized that Dasa describes delivery of PARP-1 inhibitors such as AZ7379 to cardiac tissue as a potential treatment in response to myocardial infarction. It would be recognized that omecamtiv mecarbil enables the targeting of similar myocardial tissue to the peptides of Dasa, as omecamtiv mecarbil is specific to cardiac myosin.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the liposomes containing a DSPE-PEG-omecamtiv mecarbil cardiac myosin targeting vector taught by the combination of Biswas and Malik by loading the targeted liposomes with a PARP-1 inhibitor such as AZ7379 as taught by Dasa because this modification would enable the use of the omecamtiv mecarbil liposomes for drug delivery to treat myocardial infarction in the same way as the liposomes of Dasa (MPEP § 2143(I)(C)). This would predictably result in a liposome comprising a cardiac myosin targeting vector comprising omecamtiv mecarbil, a linker, and a lipid anchoring moiety loaded with the therapeutic agent AZ7379 for the treatment of myocardial infarction.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this modification because the liposomes of Dasa and Biswas (and thus the combination of Biswas and Malik) are similar in composition. Thus, it would be expected that if AZ7379 can be loaded into the liposomes of Dasa, it could also be loaded by similar methods into the liposome of Biswas and Malik. Additionally, the skilled artisan in liposome art is capable of multiple methods of drug loading into liposomes. The loading of Dasa demonstrates that AZ7379 is a drug suitable for loading into liposomes. There would also be a reasonable expectation of success using the AZ7379 loaded omecamtiv mecarbil liposomes in the treatment of myocardial infarction because Dasa teaches that myocardial targeting of PARP-1 inhibitors is useful for such a method of treatment and demonstrates that myocardial tissue targeting liposomes can effectively release AZ7379 to elicit a desired pharmacological effect in myocardial cells.
The skilled artisan would have been motivated to make this modification because Dasa teaches that the AZ7379 PARP-1 inhibition can be used to treat myocardial infarction. Thus, loading the liposomes of Biswas and Malik with the same compound would enable the use of the omecamtiv mecarbil liposomes for cardiac drug delivery applications.
Regarding claim 6, as described above, the combined teachings of Biswas and Malik teach a liposome comprising a cardiac myosin targeting vector containing an omecamtiv mecarbil head group conjugated to a DSPE lipid anchoring/solubilizing moiety by a PEG linker molecule, rendering claim 1 obvious. Furthermore, Biswas teaches incorporation of the DSPE-PEG-myosin targeting molecule vector into a liposome (liposomal carrier) wherein the DSPE anchoring moiety is anchored within the lipid bilayer of the liposome and the head myosin targeting molecule extends outwardly from the liposome (pg. 2005, Abstract Figure). The examiner interprets this incorporation to decorate the liposome with the targeting vector. Additionally, Dasa teaches loading a cardiac targeting liposome with AZ7379 (pg. 559, Section 2.2.9). The examiner interprets AZ7379 to be a cargo molecule contained by the liposome. As described above, it would have been prima facie obvious to load the omecamtiv mecarbil liposomes of Biswas and Malik with the AZ7379 cargo of Dasa, producing an AZ7379-loaded DSPE-PEG-omecamtiv mecarbil containing liposome. Therefore, the combined teachings of Biswas, Malik, and Dasa render claim 6 obvious.
Regarding claim 7, Dasa teaches that AZ7379 is a PARP-1 inhibitor (pg. 557, left column, paragraph 2). The examiner thus interprets the molecule to be a therapeutic drug. Therefore, the combined teachings of Biswas, Malik, and Dasa render claim 7 obvious.
Regarding claim 8, Biswas teaches a liposome containing a cardiac myosin targeting vector wherein the linker molecule comprises polyethylene glycol (pg. 2005, Abstract Figure; Figure 1; pg. 2007, left column, paragraphs 2 and 3). As described above, the liposome of the combination of Biswas and Malik comprises DSPE-PEG-omecamtiv mecarbil wherein PEG is the linker group. Therefore, the combined teachings of Biswas, Malik, and Dasa render claim 8 obvious.
Regarding claim 13, for the reasons provided above in the rejection of claim 1, the cardiac myosin targeting vector of the myosin targeting liposomes taught by the combination of Biswas and Malik render obvious the cardiac myosin targeting vector of claim 13 wherein the head group is omecamtiv mecarbil, the lipid anchoring/solubilizing moiety is DSPE, and the linker is PEG. Additionally, Dasa teaches loading cardiac tissue targeting liposomes with AZ7379, a PARP-1 inhibitor that may be used in the treatment of myocardial infarction (pg. 559, Section 2.2.9; pg. 557, left column, paragraph 2; and Figure 6). The examiner thus interprets AZ7379 to be a cardiac-treating drug. Thus, the combination of these teachings would result in the use of the DSPE-PEG-omecamtiv mecarbil liposomes loaded with a cardiac treating drug for targeted drug delivery in myocardial infarction. The treatment process would involve administering the liposome to the subject (Dasa teaches in vivo administration of cardiac targeting liposomes to cardiac tissue – Figures 3 and 4) and the liposome would contain a cardiac treating drug. Therefore, the method would involve administering both a cardiac treating drug and a liposome containing the claimed cardiac myosin targeting vector. Therefore, the combined teachings of Biswas, Malik, and Dasa render claim 13 obvious.
Regarding claim 15, as described above, the combined teachings of Biswas and Malik teach a liposome comprising a cardiac myosin targeting vector containing an omecamtiv mecarbil head group conjugated to a DSPE lipid anchoring/solubilizing moiety by a PEG linker molecule, rendering claim 1 obvious. Furthermore, Biswas teaches incorporation of the DSPE-PEG-myosin targeting molecule vector into a liposome (liposomal carrier) wherein the DSPE anchoring moiety is anchored within the lipid bilayer of the liposome and the head myosin targeting molecule extends outwardly from the liposome (pg. 2005, Abstract Figure). The examiner interprets this incorporation to decorate the liposome with the targeting vector. Additionally, Dasa teaches loading a cardiac targeting liposome with AZ7379 (pg. 559, Section 2.2.9). The examiner interprets AZ7379 to be a cargo molecule contained by the liposome. As described above, it would have been prima facie obvious to load the omecamtiv mecarbil liposomes of Biswas and Malik with the AZ7379 cargo of Dasa, producing an AZ7379-loaded DSPE-PEG-omecamtiv mecarbil containing liposome. Therefore, the combined teachings of Biswas, Malik, and Dasa render claim 15 obvious.
Regarding claim 16, Dasa teaches that AZ7379 can be loaded into liposomes and used to inhibit PARP-1 to treat myocardial infarction (pg. 559, Section 2.2.9; pg. 557, left column, paragraph 2; and Figure 6). Therefore, the combined teachings of Biswas, Malik, and Dasa render claim 16 obvious.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Biswas, Malik, and Dasa as applied to claims 6-8, 13, 15, and 16 above, and further in view of Ofori (Ofori, S. and Awuah, S. G., ACS Omega, 2019).
As described above, Biswas teaches liposomes for targeted delivery of therapeutics comprising antibody-linked PEG-DSPE (pg. 2007, left column, paragraphs 2 and 3). Biswas teaches that the liposomes can be prepared using a 2G4 monoclonal antibody (pg. 2007, left column, paragraph 3), which is specific for cardiac myosin (pg. 2006, right column, first paragraph). Biswas teaches that liposomes can be used as drug delivery systems (pg. 2005, Introduction, paragraph 1). Additionally, Malik teaches the direct activator of cardiac myosin omecamtiv mecarbil (pg. 1439, Abstract; and pg. 1440, Figure 1A). Malik teaches that omecamtiv mecarbil directly binds to cardiac myosin S1 protein (pg. 1441, Figure 2). Malik teaches that omecamtiv mecarbil increases cardiac myocyte contractility while not changing the calcium homeostasis (pg. 1441, Figure 3). Additionally, Dasa teaches drug-loaded targeted liposomes for the treatment of myocardial infarction (pg. 556, Abstract). Dasa also teaches loading the myocardial targeting liposomes with AZ7379 (pg. 559, Section 2.2.9), which is a PARP-1 inhibitor (pg. 557, left column, paragraph 2). Dasa teaches that the targeted liposomes accumulate in myocardial tissue in a post-MI heart (pg. 563, Figure 4). Dasa teaches that the AZ7379 loaded liposomes can be used to reduce PARP-1 function in cardiomyocytes (pg. 565, Figure 6). Dasa suggests using such a drug loaded liposome to deliver cell type specific therapeutic molecules to improve cardiac function following a myocardial infarction (pg. 565, left column, paragraph 1). As described above, the combined teachings of Biswas, Malik, and Dasa teach AZ7379-loaded liposomes comprising a cardiac myosin targeting vector containing an omecamtiv mecarbil head group conjugated to a DSPE lipid anchoring/solubilizing moiety by a PEG linker molecule that can be used for myocardial drug delivery to treat myocardial infarction.
The combined teachings of Biswas, Malik, and Dasa do not teach directly linking the cardiac-treating drug to the cardiac myosin targeting vector.
Ofori teaches PARP inhibitor conjugates (pg. 12584, Abstract). More specifically, Ofori teaches the conjugation of an olaparib derivative to BMS-001, a PD-L1 inhibitor (pg. 12585, Figure 1; and pg. 12586, Scheme 1). Ofori teaches that the combination of the drugs is more effective than the individual therapeutics (pg. 12588, Figure 3).
A person of ordinary skill in the art would have recognized that both the AZ7379 of Dasa and the olaparib of Ofori are PARP inhibitors. It would also be recognized that Malik teaches omecamtiv mecarbil is a drug molecule. It would further be recognized that Ofori teaches that PARP inhibitors can be covalently linked to other drug compounds.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the AZ7379 loaded DSPE-PEG-omecamtiv mecarbil system of the combination of Biswas, Malik, and Dasa by covalently linking the AZ7379 to the omecamtiv mecarbil group in the way that Ofori teaches covalently linking a PARP inhibitor to another drug because this linkage chemistry was a feature known in the art and one of ordinary skill in the art could have combined these elements by known methods with no change in their respective functions (MPEP § 2143(I)(A)). This modification would have yielded the predictable outcome of DSPE-PEG-omecamtiv mecarbil containing liposomes wherein AZ7379 is covalently linked to the cardiac myosin targeting vector.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this modification because, as described above, a practitioner in targeted liposomes is capable of using and performing various reactions to conjugate molecules. Additionally, Ofori demonstrates a means of connecting a PARP inhibitor to another drug molecule.
The skilled artisan would have been motivated to make this modification to provide the PARP inhibitor at the surface of the liposome rather than in the inside requiring release of the compound after targeting to the tissue. This would allow for making the liposome more stable without inhibiting the drug release properties necessary for PARP inhibitor to be active.
Regarding claim 14, as described above, the combined teachings of Biswas and Malik teach a liposome comprising a cardiac myosin targeting vector containing an omecamtiv mecarbil head group conjugated to a DSPE lipid anchoring/solubilizing moiety by a PEG linker molecule, rendering claim 1 obvious. Additionally, Dasa teaches using cardiac targeting liposomes to deliver PARP inhibitors to treat myocardial infarction (Section 2.2.9; Figure 3; Figure 5; and Figure 6). Additionally, Ofori teaches conjugation of a PARP inhibitor to another drug molecule (Scheme 1). As described above, it would have been prima facie obvious in view of Ofori to link the AZ7379 of Dasa to the omecamtiv mecarbil head group of the cardiac myosin targeting vector of Biswas and Malik. Furthermore, Biswas teaches incorporation of the DSPE-PEG-myosin targeting molecule vector into a liposome (liposomal carrier) wherein the DSPE anchoring moiety is anchored within the lipid bilayer of the liposome and the head myosin targeting molecule extends outwardly from the liposome (pg. 2005, Abstract Figure). The examiner interprets this incorporation to decorate the liposome with the targeting vector. Additionally, Dasa teaches using the cardiac targeted PARP inhibitor in the treatment of myocardial infarction (pg. 559, Section 2.2.9; pg. 557, left column, paragraph 2; and Figure 6). The examiner thus interprets AZ7379 to be a cardiac-treating drug. Therefore, the combined teachings of Biswas, Malik, Dasa, and Ofori render claim 14 obvious.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Malik in view of Mou (Mou, T.; et al., J. Nucl. Med., 2012).
As described above, Malik teaches the direct activator of cardiac myosin omecamtiv mecarbil (pg. 1439, Abstract; and pg. 1440, Figure 1A). Malik teaches that omecamtiv mecarbil directly binds to cardiac myosin S1 protein (pg. 1441, Figure 2). Malik teaches that omecamtiv mecarbil increases cardiac myocyte contractility while not changing the calcium homeostasis (pg. 1441, Figure 3). Malik suggests that cardiac myosin activation by omecamtiv mecarbil may provide a therapeutic approach for systolic heart failure (pg. 1439, Abstract).
Malik does not teach an omecamtiv mecarbil analog or derivative comprising either Structure I, Structure II, or Structure II as recited in claim 9.
Mou teaches 18F labeled myocardial imaging agents (pg. 472, Abstract). More specifically, Mou teaches 18F-FP1OP and 18F-FP3OP (pg. 473, Figure 1). Mou describes these molecules as pyridaben derivatives (pg. 473, left column, paragraph 2). Mou teaches that the 18F labeled imaging agents are selective to heart tissue (pg. 476, Table 1). Mou teaches that the radiolabeled molecules can be used for imaging in vivo (pg. 477, Figures 4 and 5). Mou teaches that the molecules can be used for PET imaging of myocardial perfusion in chronic myocardial ischemia (pg. 478, Figure 6).
A person of ordinary skill in the art would have recognized that both the pyridaben derivative imaging agents of Mou and the omecamtiv mecarbil of Malik are myocardial tissue targeting compounds. It would be recognized that Mou teaches that 18F labeling enables the use of a molecule for PET imaging. It would also be recognized that Mou teaches that 18F labeling can be done by addition of an alkoxy group to a phenyl moiety.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the omecamtiv mecarbil molecule of Malik with the alkoxy 18F-labeled groups as taught by Mou because Mou teaches that these radionuclide containing groups allow using the molecule for PET imaging in myocardial applications (MPEP § 2143(I)(C)). This would predictably result in an omecamtiv mecarbil derivative with an 18F label attached via an alkoxy group attached to the central phenyl moiety of the molecule.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this substitution because Mou teaches that pyridaben derivatives are myocardial targeting similar to omecamtiv mecarbil of Malik. Additionally, the chemist of ordinary skill would be capable of reactions to attach alkoxy groups to phenyl rings. Attachment to the central phenyl ring at the position of the fluorine in omecamtiv mecarbil is especially likely for success because the fluorine is a better leaving group than the hydrogens on other carbons of this phenyl ring, making it a more reactive carbon.
The skilled artisan would have been motivated to make this modification to turn omecamtiv mecarbil into a cardiac myosin targeting PET imaging agent.
Regarding claim 9, Malik teaches omecamtiv mecarbil (pg. 1440, Figure 1A). Additionally, Mou teaches modifying phenyl moieties of cardiac targeting molecules with 18F-labeled alkoxy groups (pg. 473, Figure 1; pg. 476, Table 1). As described above, it would have been prima facie obvious to incorporate the radiolabeled alkoxy groups of Mou (Figure 1) at the central phenyl of omecamtiv mecarbil where the fluorine is, substituting the fluorine at that position. The resulting products would read on the structures of Structure I and Structure III of claim 9. Using the alkoxy group of 18F-FP1OP of Mou would result in a molecule of Structure I wherein n is 2. Using the alkoxy group of 18F-FP3OP of Mou would result in a molecule of Structure III wherein n is 2, X is 18F, and Z is a carbamoyl group. Therefore, the combined teachings of Malik and Mou render claim 9 obvious.
Claims 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Malik and Mou as applied to claim 9 above, and further in view of Senior.
As described above, Malik teaches the direct activator of cardiac myosin omecamtiv mecarbil (pg. 1439, Abstract; and pg. 1440, Figure 1A). Malik teaches that omecamtiv mecarbil directly binds to cardiac myosin S1 protein (pg. 1441, Figure 2). Furthermore, Mou teaches 18F labeled myocardial imaging agents (pg. 472, Abstract). More specifically, Mou teaches 18F-FP1OP and 18F-FP3OP (pg. 473, Figure 1). Mou teaches that the molecules can be used for PET imaging in vivo (pg. 478, Figure 6). As described above, the combination of Malik and Mou results in compounds that read on structures I and III and claim 9 that are cardiac myosin targeted PET imaging agents.
The combined teachings of Malik and Mou do not teach further linking a cargo molecule thereto.
As described above, Senior teaches the use of 99mTc labeled antimyosin antibodies for imaging (pg. 536, Abstract). More specifically, Senior teaches labeling an antimyosin antibody with 99mTc directly or by conjugation of an RP-1 chelator to the antibody and subsequently complexing 99mTc in the chelator (pg. 537, Isotope Labeling). Senior teaches using the 99mTc labeled antimyosin antibodies to image myocardial infarction (pg. 537, Antimyosin Imaging; pg. 538, Antimyosin Antibody Imaging; pg. 539, Figures 1 and 2). Senior teaches that 99mTc labeled antimyosin antibody is an effective diagnostic tool for early imaging of myocardial infarction (pg. 541, last paragraph).
A person of ordinary skill in the art would have recognized that both the antibodies of Senior and the omecamtiv mecarbil molecule of Malik are molecules that selectively bind to cardiac myosin protein. It would be recognized that Senior teaches that a myosin binding molecule can be labeled with 99mTc to enable its use in cardiac imaging.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the omecamtiv mecarbil derivative of the combination of Malik and Mou by modifying the derivative with a 99mTc label as taught by Senior because this modification would enable SPECT imaging of the molecule in biological systems and cardiac tissue in the same way the label was used by Senior with respect to the antimyosin antibody (MPEP § 2143(I)(C)). This would predictably result in an omecamtiv mecarbil derivative with dual PET and SPECT imaging capabilities.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this modification because a practitioner in radionuclide labeling is capable of using and performing various reactions to conjugate chelating moieties to targeting molecules, such as the RP-1 chelator attachment taught by Senior. As the omecamtiv mecarbil derivative of the combination of Malik and Mou contain various functional groups, standard chemistry methods could be used to use or create reactive handles for conjugation of a chelator to the molecule.
The skilled artisan would have been motivated to make this modification because Senior teaches that the 99mTc radiolabel enables the use of the molecule for imaging applications. The radionuclide 99mTc is a known SPECT imaging radionuclide. Thus, its incorporation would enable dual SPECT and PET imaging using the omecamtiv mecarbil derivative molecule.
Regarding claims 10 and 11, as described above, the combined teachings of Malik and Mou teach omecamtiv mecarbil derivatives that read on Structure I and Structure III of claim 9, rendering the claim obvious. Additionally, Senior teaches radiolabeling a myosin binding/targeting molecule with 99mTc (pg. 537, Isotope Labeling). One method of Senior involves the ligation of an RP-1 chelator to the myosin targeting molecule followed by coordination of the 99mTc radionuclide (pg. 537, Isotope Labeling). As described above, it would have been prima facie obvious to apply the labeling methods of Senior to the omecamtiv mecarbil derivative taught by the combination of Malik and Mou. The resulting combination would produce a chelator-conjugated omecamtiv mecarbil derivative complexed or conjugated to 99mTc. The examiner interprets the radionuclide coordinated chelating group to be a cargo molecule linked to the omecamtiv mecarbil analog or derivative. Therefore, the combined teachings of Malik, Mou, and Senior render claims 10 and 11 obvious.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Malik and Mou as applied to claim 9 above, and further in view of Biswas.
As described above, Malik teaches the direct activator of cardiac myosin omecamtiv mecarbil (pg. 1439, Abstract; and pg. 1440, Figure 1A). Malik teaches that omecamtiv mecarbil directly binds to cardiac myosin S1 protein (pg. 1441, Figure 2). Furthermore, Mou teaches 18F labeled myocardial imaging agents (pg. 472, Abstract). More specifically, Mou teaches 18F-FP1OP and 18F-FP3OP (pg. 473, Figure 1). Mou teaches that the molecules can be used for PET imaging in vivo (pg. 478, Figure 6). As described above, the combination of Malik and Mou results in compounds that read on structures I and III and claim 9 that are cardiac myosin targeted PET imaging agents.
The combined teachings of Malik and Mou do not teach disposing the omecamtiv mecarbil within a liposomal carrier.
As described above, Biswas teaches liposomes for targeted delivery of therapeutics (pg. 2005, Abstract). More specifically, Biswas teaches preparing liposomes with egg phosphatidyl choline, cholesterol, and antibody-linked PEG-DSPE (pg. 2007, left column, paragraphs 2 and 3). The Antibodies are conjugated to the DSPE phospholipid via modifications to the end of the PEG linker wherein a hydrazine-modified PEG reacts with an aldehyde modified antibody (pg. 2006, last paragraph; Figure 1; pg. 2007, left column, paragraphs 1-3). Biswas teaches that the liposomes can be prepared using a 2G4 monoclonal antibody (pg. 2007, left column, paragraph 3), which is specific for cardiac myosin (pg. 2006, right column, first paragraph). Biswas teaches that the 2G4-modified liposomes bind to cardiac myosin in vitro (pg. 2010, Figure 4b). Biswas teaches that liposomes can be used as drug delivery systems (pg. 2005, Introduction, paragraph 1).
A person of ordinary skill in the art would have recognized that both the 2G4 antibody of Biswas and the omecamtiv mecarbil molecule of Malik (and thus the omecamtiv mecarbil derivative of the combination of Malik and Mou) are molecules that selectively bind to cardiac myosin protein. It would also be recognized that Biswas teaches that targeted liposomes are useful for drug delivery applications.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the cardiac myosin-binding omecamtiv mecarbil derivative of the combination of Malik and Mou by attaching it to DSPE-PEG and using it as a myosin targeting group in a liposome as taught by Biswas because this would enable using the omecamtiv mecarbil derivative as a targeting group for myocardial drug delivery (MPEP § 2143(I)(C)). This modification would predictably result in a liposome comprising DSPE-PEG conjugated to an omecamtiv mecarbil derivative.
A person of ordinary skill in the art would have had a reasonable expectation of success in making this modification because a practitioner in targeted liposomes is capable of using and performing various reactions to conjugate targeting moieties to linker and lipid groups, such as the hydrazone linkage taught by Biswas.
The skilled artisan would have been motivated to make this modification because it allows the omecamtiv mecarbil derivative to be used for drug delivery applications. The inclusion of the 18F label in the derivative would enable concomitant PET imaging of the liposomes in vivo. This would allow the user to determine the in vivo location of the liposomes, monitoring off-target distribution to avoid toxicity.
Regarding claim 12, as described above, the combined teachings of Malik and Mou teach omecamtiv mecarbil derivatives that read on Structure I and Structure III of claim 9, rendering the claim obvious. Additionally, Biswas teaches attaching a myosin targeting molecule to PEG-DSPE and incorporating it into a liposome (Abstract Figure; and pg. 2007 left column, paragraphs 2 and 3). As described above, it would have been prima facie to incorporate the omecamtiv mecarbil derivative of Malik and Mou in the liposome in place of the antibody. As Biswas teaches that the DSPE incorporates into the liposome bilayer (Abstract Figure), the examiner interprets this to mean that the omecamtiv mecarbil derivative is disposed within a liposomal carrier. Therefore, the combined teachings of Malik, Mou, and Biswas render claim 12 obvious.
Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
As pertinent art, the examiner cites Marques-Gallego (Marques-Gallego, P. and de Kroon, A. I. P. M., BioMed. Res. Int., 2014). Marques-Gallego teaches ligation strategies used in targeted liposomes used for imaging and drug delivery (pg. 1, Title and Abstract). Marques teaches examples of chemistry strategies for linking ligands to liposomes (pg. 3, Figure 1; pg. 4, Figure 2; and pg. 6, Figure 3). Marques summarizes and cites several examples of ligand conjugation to modified DSPE and DSPE-PEG lipids in liposomes (pg. 2, right column, paragraph 3; pg. 4, right column, last paragraph; pg. 6, right column, first paragraph; and pg. 7, left column, last paragraph). The examiner notes that this reference demonstrates that the skilled artisan in targeted liposomes is capable of linking targeting molecules to lipid anchors by several different chemistries, allowing attachment of various ligands or modified ligands.
As pertinent art, the examiner cites Banerjee (Banerjee, S. R.; et al., J. Med. Chem., 2013). Banerjee teaches a 99mTc labeled PSMA targeting compound for imaging applications (pg. 6108, Abstract). Banerjee teaches three different chelators coordinated with 99mTc attached to a PSMA targeting small molecule in multiple ways (pg. 6109-6110, Figure 1; Schemes 1-5). Banerjee teaches using the radiolabeled small molecule for SPECT-CT imaging (pg. 6111, Figure 2; and pg. 6112, Figures 3 and 4). The examiner notes that this reference demonstrates that the skilled artisan in radiolabeling is capable of attaching multiple chelators capable of coordinating 99mTc to small molecule compound by using various chemistry reactions and tools.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric P Mosher whose telephone number is (571)272-3258. The examiner can normally be reached Monday-Friday 9am-5pm.
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/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
