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 .
Election/Restrictions
Applicant’s election of group I and species of CD4 (with SEQ ID NOs. 84 and 86 for the antigen-biding construct and 123I as the radionuclide) with SPECT imaging and CD6 (with SEQ ID NOs. 35 and 29 for the antigen-biding construct and 89Zr as the radionuclide with PET imaging) as the target for each administration step; the immune contexture is reported as an immunoscore and the subject has a disease, the disease being solid tumor in the reply filed on August 19, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Specification
The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
Claim 31 requires the reporting of the immune contexture as an immunoscore, which renders the definition of “immunoscore” essential subject matter. However, when discussing this term in specification (see ¶ [0123] of the PGPub of the instant application), exemplary definitions are set forth by citations to various non-patent literature documents, resulting in an improper incorporation by reference. While these are prefaced by “e.g.” and therefore do not form a limiting definition of immunoscore, examples within the scope are essential for one of ordinary skill to determine the scope of “immunoscore”.
Claim Objections
Claim 1 is objected to because of the following informalities: abbreviations such as “IFN” in “IFN-gamma are not accompanied by the complete word or phrase the first time they appear in the claims. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3 – 6, 11, 12, 15, 25, 29, 29 – 31, 57, 64 and 65 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
A generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus. The problem is especially acute with genus claims that use functional language to define boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention the achieves the claimed results and do so by showing that that the applicant has invented species sufficient to support a claim to a functionally-defined genus.
The claims require a radionuclide tracer as part of antigen-binding constructs, that are chemical compounds commonly referred to as proteins, that binds to any part of any one of the 4 targets recited in claim 1 – CD3, CD4, IFN-gamma and CD8 – and can be all varieties of antibodies, including binding fragments thereof (see ¶ [0128] of the PGPub of the instant application). The sequence of the antigen-binding constructs are only specified in dependent claims 64 – 66 but even those are not limiting as reference is made to various figures containing sequences and the claims encompass those with “at least about 80%” identity to the referenced figures and the SEQ ID NOs present therein. The Examiner reviewed the specification and while the figures indicate the target (e.g., chimeric IAB-huCD8 minibody VL-VH sequence) of a particular SEQ ID NO, affinity or other data that might permit determination of a structure-function relationship between the amino acid sequences disclosed and the binding targets are not provided. At least about 80% identity allows for about 20% of the amino acids to be different and the changes need not be conservative substitutions. The species is also not limited and therefore the claimed method could be carried out with non-human subjects such as rats or mice that may encompass sequences that bind to these molecules from one species but not another and there is no guidance on this aspect and what changes may or may not be necessary.
Therefore while various sequences were present in the disclosure as originally filed that constitute some species within the claimed genus of antigen-binding constructs, these disclosed species do not form a representative number of species within the claimed genus to fully satisfy the written description requirement for the claims. The dependent claims fall therewith as the subject matter of the dependent claims as the scope of the claims does not result in the disclosed species being a representative number of species within the claimed genus.
Claim Rejections - 35 USC § 112 – Scope of Enablement
Claims 1, 3 – 6, 11, 12, 15, 25, 29, 29 – 31, 57, 64 and 65 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for disclosed sequences that bind to at least one of CD3, CD4, IFN-gamma and CD8, does not reasonably provide enablement for the complete scope of antigen binding constructs with the claimed function or those with the claimed function that are at least about 80% identical to the claimed figures. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The disclosure and claims of the application have been compared per the factors indicated in the decision In re Wands, 8 USPQ2nd 1400 (Fed. Cir. 1988) as to undue experimentation
The factors include:
1. The nature of the invention;
2. The breadth of the claims;
3. The predictability or unpredictability of the art;
4. The amount of direction or guidance presented;
5. The presence or absence of working examples
6. The quantity of experimentation necessary;
7. The state of the prior art; and
8. The relative skill of those skilled in the art.
Each relevant factor is addressed below on the basis of comparison of the disclosure, the claims and the state of the art in the assessment of undue experimentation.
The nature of the invention; the breadth of the claims:
The claims are drawn to an imaging method using two radionuclides with two antigen-binding constructs that bind to different targets selected from the list of CD3, CD4, IFN-gamma and CD8, with parameters estimated from positron emission tomography (PET) or single photon emission computed tomography (SPECT) that are then used to generate an image based on the distribution and/or abundance of the targets or cells expressing the target. In all but claims 64 and 65, there are no limitations on the antigen-binding construct as long as the construct is any variety of antibody or fragment thereof (see ¶ [0128] of the PGPub of the instant application for the definition of antigen-binding fragment). Claims 64 and 65 make reference to figures containing various SEQ ID NOs. and encompass amino acid sequences that are at least about 80% identical to one of the referenced figures that binds to CD8 (claim 64) or CD4 (claim 65).
The predictability or unpredictability of the art; the amount of direction or guidance presented; the presence or absence of working examples; the quantity of experimentation necessary; the state of the prior art; the relative skill of those skilled in the art:
The level of skill of those skilled in the art is high, such as a researcher with a PhD carrying out research in the area of immunology.
The claimed antigen-binding constructs are almost all defined by function, although amino acid sequences as disclosed or with at least about 80% identity to such sequences are required by claims 64 and 65. Techniques are known to such artisans wherein antigens can be generated in vivo to generate whole antibodies. Such materials fall within the scope of the claims but the claims also encompass only portions of antibodies that retain the ability to bind to the antigen.
In the disclosure as filed, protocols are set forth for carrying out the claimed method but no results of administering radiolabeled antigen-binding constructs to a subject although the collection of PET and/or SPECT images is known to those of skill in the art or even in vitro binding experiments demonstrating the affinity of the disclosed sequences for a particular target. Sequences for various targets are presented in the disclosure but there does not appear to be binding data for any of sequences given to the targets although in some figures there are boxed regions that could be the CDR (complementarity-determining region) although that information is only present in the brief description of Figs 84A – 84I and may not apply to all other figures. Even if binding data was present, the claims referencing figures with specific SEQ ID Nos. permit variation as the amino acid sequences claimed only have to have at least about 80% identity to disclosed amino acid sequences and no guidance has been given for maintaining the ability to bind to the desired target and without disrupting the overall structure of the sequence.
One of ordinary skill in the art could generate antibodies, test for binding to at least one of the claimed targets or from an antibody known to bind to a given target, replace amino acids in the sequence of that antibody to determine what, if any, effect on function of binding to at least one of the cited targets occurred. Even claims 64 and 65 encompass amino acid sequences not disclosed in the disclosure as originally filed given the broadening of claim scope due to at least about 80% identity to the disclosed sequence being required and those represent only a small number of possible antigen-binding constructs that bind to at least one of CD3, CD4, IFN-gamma and CD8. The lack of common element leading to binding to a required target by either of those general methods that are known in art rendering such experimentation undue. Therefore the full scope of the claims is not enabled as undue experimentation is required.
Claim Rejections - 35 USC § 112 – Indefiniteness
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, 3 – 6, 11, 12, 15, 25, 29, 29 – 31, 57, 64 and 65 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The metes and bounds of the claims cannot be determined as the definition of “immune contexture” in the last two lines of claim 1 and “immunoscore” in claim 31 cannot be determined. This is due in part to the improper incorporation by reference in the specification discussed above. It is not clear if any image based on the distribution and/or abundances of the targets and/or cells expressing the targets is considered to provide an immune contexture or if more is required to be considered “an indication of the immune contexture of the one or more tissues” as recited in claim 1. Claim 31 requires that the immune contexture be an immunoscore but what that is and how it differs from the immune contexture is not clear. Withdrawn claim 32 indicates possible biomarkers that can be used in an immunoscore that were not elected, but what values, how many values, the possible relationships (e.g., summation or division) can be used in formulating an immunoscore are not clear in part because of the improper incorporation by reference.
The dependent claims fall therewith.
Please clarify.
For the purposes of applying art below, the wherein clause at the end of claim 1 is being interpreted as characterizing the results of the steps explicitly recited previously in claim 1 and also reading on the immunoscore of claim 31. "A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim." Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1172 (Fed. Cir. 1993). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.") MPEP 2111.04
Claim 4 is 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. Claim 4 recites the limitation "the third target" in lines 7 and 9. There is insufficient antecedent basis for this limitation in the claim. Please clarify.
Claim 11 is 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. Claim 11 recites the limitation "the radionuclide tracer" in line 2 and “the antigen-binding construct” in line 3. There is insufficient antecedent basis for this limitation in the claim because claim 1, from which claim 11 depends, recites a first and second radionuclide and a first and second antigen-construct so it is not clear which radionuclide(s) and which antigen-binding construct(s) are being referenced in claim 11. Please clarify.
Claim 29 is 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. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 29 recites the broad recitation “an infectious disease”, and the claim also recites “including without limitation, viral, bacterial, or fungal infections” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Please clarify.
Claims 62, 64 and 65 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. Each claim recites the limitation "the antigen-binding construct" in line 2. There is insufficient antecedent basis for this limitation in the claim because claim 1, from which each claim depends, recites first and second antigen-constructs so it is not clear which antigen-binding construct(s) are being referenced in each claim. Please clarify.
Claims 64 and 66 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. Reference to specific figures “is permitted only in exceptional circumstance where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim” (MPEP 2173.05(s)). Those exceptional circumstances are not present in the instant claims as the materials being referenced are SEQ ID NOs, which is a direct way of claiming the subject matter present in each referenced figure.
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.
Claim(s) 1, 3 – 6, 11, 12, 15, 25, 29, 29 – 31 and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Rubin et al. (WO 98/00560) in view of Tavare et al. (J Nucl Med, 2015; all citations from HHS Public Access Version submitted with IDS filed August 19, 2025) and Ostoumov et al. (Cell Mol Life Sci, 2018).
Rubin et al. discloses methods for determining lymphocyte distribution and trafficking in mammal by administering a labeled ligand capable of interacting specifically with lymphocytes and then imaging to determine the lymphocyte distribution and trafficking (whole document, e.g., abstract). In certain embodiments, it is preferred that the lymphocytes are CD4+ or CD8+ cells (p 2, ln 32 – 33). The ligand can be antibodies such as polyclonal or monoclonal antibodies, an antibody fragment or recombinant antibody (p 2, ln 33 – p 3, ln 3). Suitable labels include gamma emitters such as iodine-123 or a positron emitter (p 3, ln 3 – 5). The administered ligand interacts with the lymphocytes to label the lymphocytes (p 6, ln 29 – 31) and the distribution of the labeled lymphocytes is determined by an imaging technique (p 6, ln 32 – 33). Gamma emitters can be determined using techniques such as a SPECT camera and positron emitters can be determined by a PET camera (p 7, ln 2 – 5). The timing of imaging after administration of the labeled ligand can be minutes, hours, days, weeks or months depending factors such as the type and amount of label and can be determined by one of ordinary skill in the art employing such factors using no more than routine experimentation (p 7, ln 11 – 14). The mammal can have a disease such as a malignancy (p 2, ln 30 – 31). The method can also be used to diagnose the degree of progression of a disease in a mammal such as solid tumor malignancies and is particularly useful for diseases in which immunomodulating therapy might be useful (p 8, ln 20 – 26).
The positron emitter 89Zr for PET imaging is not disclosed and the explicit combination of antigen-binding constructs for both CD4 and CD8 is not disclosed.
Tavare et al. discloses that whole body immunoPET offers the potential to provide spatial and temporal information about immune cell subtypes that is impossible utilizing current methods (p 2, ¶ 1 of introduction). ImmunoPET takes advantage of the exquisite specificity and affinity of antibodies or antibody fragments and the sensitivity of PET (p 2, ¶ 2 of Introduction). Anti-CD4 and anti-CD8 cDBs (cys-diabodies) radiolabeled with 89Zr were developed for direct immunoPET detection of CD4+ and CD8+ T cells with the goal of detecting helper (CD4+) and cytotoxic (CD8+) lymphocytes after HSC (hematopoietic stem cell) therapy (p 3, ¶ 2). Both the 89Zr labeled anti-CD4 GK1.5 Cys diabody and anti-CD8 2.43 antibody targeted the respective type T cells in vivo (p 4, ¶ 4 – 6 and p 5, ¶ 4 – 5 respectively). microPET was used to monitor T cell repopulation post-HSC transplant with demonstrated specificity for either CD4 or CD8 (p 7, ¶ 1) in a robust method that will greatly aid the ability to monitor the dynamic nature of T cell subsets in models of disease and expand the knowledge of both T cells in vivo and immunotherapies (p 8, ¶ 4).
Ostoumov et al. discloses that CD4 and CD8 T cell responses are part of the cancer immune cycle and both populations significantly influence the clinical outcome (abstract). For cellular immunity the relationship between CD4 and CD8 cells for tumor suppression is a special feature of the immune system with these two types of cells are derived from the adaptive arm of the immune system and require antigen experience to trigger antitumor immunity (p 699, col 1, ¶ 2). CD4 and CD8 T cells are involved in all of the central components of the failure of tumor rejection as shown in Figure 2 with any disruption of mutual CD4/CD8 T cell interplay or other crucial T cell signaling steps abort the whole cancer immune cycle (Figure 2). Different cancer immunotherapy strategies are designed to activate or reactivate the therapeutic antitumor activity in the immune system (p 702, col 1, ¶ 3).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use antigen-binding constructs that bind CD4+ and CD8+ lymphocytes labeled with respectively with 123I imaged using SPECT and 89Zr images using PET to determine the distribution and trafficking of CD4+ and CD8+ lymphocytes in a subject with a solid tumor. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Rubin et al. discloses that the distribution and trafficking of lymphocytes such as those positive for CD4 or CD8 can be useful in diagnosing the degree of progression of diseases such as solid tumors, particularly for diseases in which immunomodulating therapy might be useful. Ostoumov et al. discloses the importance of the interplay between CD4 and CD8 in controlling tumor growth and also discloses the possible use of immunotherapy in that context. Tavare et al. uses immunoPET to determine both lymphocyte types using constructs labeled with the same radiolabel. However, the use of the same label for to determine both CD4 and CD8 requires sufficient time between administration and scanning of the different targets for the previously administered labeled ligand to be removed from the body and/or the label to completely decay before administration of the second labeled construct. This issue can be avoided by using different isotopes that are imaged by different methods, e.g. 123I with SPECT and 89Zr with PET, such that the first labeled construct does not need to completely cleared from the body and/or the label to decay completely before administration and imaging for the second target. The timing of the administration and imaging of the labeled constructs can be determined by routine optimization as disclosed by Rubin et al. and by performing the scans in close temporal proximity due to the use of different labels imaged by different techniques, more relevant information on the interplay between CD4 and CD8 can be obtained because the changes over the course of several day or two would likely be smaller than longer time scales required for elimaition and/or decay of the previoud construct labeled with the same label as in Tavare et al. The different isotopes also require different imaging equipment and that equipment might not be available for imaging at the same time and/or same location, also resulting in administration of the differently labeled constructs being administered on different days. There is no evidence of record as to the criticality of the timing of the administration of the antigen-binding constructs to the subject.
The collection of SPECT and PET images after administration of the respective labeled antigen-binding construct results in information that estimates the distribution and/or abundance of cells expressing CD4 and CD8 respectively as required by the claims. Given the art appreciated importance of the interplay between these two types of cells, one of ordinary skill in the art would generate an image that contains information as to the distribution and/or abundance of cells expressing both markers to visualize the relationship in distribution and/or abundance of each type of cells to each other. Such information also qualifies as an immunoscore as information determined by the present methods based on a combination of two targets probed by non-invasive imaging that can provide more information about the prognosis of the cancer than information from just a single image/cell type given the importance of these two cell types and their interplay as taught by the applied prior art (see ¶ [0208] of the PGPub of the instant score discussing immune contexture and immunoscore).
Claim(s) 64 is rejected under 35 U.S.C. 103 as being unpatentable over Rubin et al., Tavare et al. and Ostoumov et al. as applied to claims 1, 3 – 6, 11, 12, 15, 25, 29, 29 – 31 and 57 above, and further in view of Gudas et al. (US 2018/0221507).
Rubin et al., Tavare et al. and Ostoumov et al. are discussed above.
A CD8 antigen-binding construct comprising SEQ ID NO: 29 fused to SEQ ID NO: 35 is not disclosed.
Gudas et al. discloses antigen binding constructs that comprise extension sequences (whole document, e.g., abstract). The antigen binding constructs can include a detectable marker such as a radioisotope (¶ [0154]). Exemplary radioisotopes include 89Zr (¶ [0184]) and constructs labeled with 89Zr were using in conjunction with PET imaging (¶ [0221]). SEQ ID NO: 162, also called IAB22C-2 (see Fig 23), is the database sequence aligned with SEQ ID NO: 29 fused to SEQ ID NO: 35 from the instant application as the query sequence and there is 100% identity of SEQ ID NO 162 to SEQ ID NOs 29 and 35 respectively outside of the gap as shown in the alignment below.
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As shown in Figure 9A, this construct binds to CD8 expressed on the surface of HPB-ALL cells.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use an 89Zr labeled antigen binding construct of IAB22C-2 of Gudas et al. as the CD8 labeling agent in the method rendered obvious by Rubin et al., Tavare et al. and Ostoumov et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Gudas et al. discloses that IAB22C-2 binds to CD8 and also can be radiolabeled and imaged using PET, rendering such a construct useful in determining the distribution and trafficking of CD8+ cells in the method of Rubin et al., Tavare et al. and Ostoumov et al.
Claim(s) 65 is rejected under 35 U.S.C. 103 as being unpatentable over Rubin et al., Tavare et al. and Ostoumov et al. as applied to claims 1, 3 – 6, 11, 12, 15, 25, 29, 29 – 31 and 57above, and further in view of Mascioni et al. (WO 2019/236684).
Rubin et al., Tavare et al. and Ostoumov et al. are discussed above.
A CD4 antigen-binding construct comprising SEQ ID NO: 84 fused to SEQ ID NO: 86 is not disclosed.
Mascioni et al. discloses antigen binding constructs that bind to CD4 (whole document, e.g., title). The modified antigen binding construct can be conjugated to a detectable marker such as radioactive substances (¶ [0171]) and exemplary radioactive substances that can be used as detectable markers includes 123I (¶ [0172]).SEQ ID NO: 15 is the database sequence aligned with SEQ ID NO 84 fused to SEQ ID NO 86 from the instant application as the query sequence and there is 100% identity of SEQ ID NO 15 with SEQ ID NOs 84 and 86 outside the gap between those two sequences as shown in the alignment
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.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use an 123I labeled antigen binding construct of SEQ ID NO: 15 of Mascioni et al. as the CD4 labeling agent in the method rendered obvious by Rubin et al., Tavare et al. and Ostoumov et al. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Gudas et al. discloses that antigen binding constructs that include SEQ ID NO:15 binds to CD4 and can be radiolabeled and imaged using SPECT, rendering the construct useful in determining the distribution and trafficking of CD4+ cells in the method of Rubin et al., Tavare et al. and Ostoumov et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618