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 .
Amendments
This action is in response to papers filed 26th Feb 2026, in which claims 57, 61, 66, and 70-71 were amended, new claims 79-83 were added, and 58, 62-65, 68-69, 72-76 were canceled. All of the amendments have been thoroughly reviewed and entered.
Applicant has amended:
Abstract to overcome objections; the previous objections are withdrawn. However, a new objection to the abstract is presented in this Office Action.
claim 57 and 67 to overcome the 112(b) rejections; the 112(b) rejections of all claims are withdrawn.
claim 71 to overcome the 112(d) rejections; the 112(d) rejections of claim 71 is withdrawn
Applicant has amended claim 57 to overcome the 112(a) rejection; the 112(a) rejection is not withdrawn.
Applicant’s arguments, see Pgs. 11 - 13, filed 21st Jan 2026, with respect to:
rejections of claims 57, 60-61, 66-67, 70-71 and 77-78 under 35 USC § 112(a) have been fully considered but are not persuasive for the reasons discussed in this office action. The 35 USC § 112(a) rejection is maintained.
Arguments applicable to amended claims are addressed below. Arguments that are no longer relevant are not addressed.
Rejections not reiterated here are withdrawn.
Status of Claims
Claims 57, 61, 66, 70-71 and 77-83 are currently under consideration.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 57-73) drawn to a method in the reply filed on 1/23/2024 was previously acknowledged. Claims 75 and 76 were withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicants subsequently canceled unelected claims 75 and 76 and added new claims 77 - 83. New claims 77 – 83 are grouped with elected Group I. With the cancellation of claims 75 - 76 in the response dated 07/10/2025, the restriction requirement was previously rendered moot.
Specification
The abstract is objected to because of the following informalities:
The abstract recites in line 1: Described herein are methods for treating a diseases such as cancer…., which is grammatically incorrect.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
In addition, Applicant is reminded of the proper language and format for an abstract of the disclosure.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
In the instant case, the abstract recites: Described herein…., as the first two words. Appropriate correction is required.
Claim Interpretation
The phrase associated with cancer cells expressing human cluster of differentiation 24 (CD24),... in the preamble is being interpreted as cancer cells overexpressing CD24. See 112b rejection below for further discussion.
The claim term “lentivirus particle” (claim 57) is not defined in the specification and so is given its broadest reasonable interpretation in light of the state of the art at the time of the invention and the specification. The specification as filed discloses the use of a “lentivirus particle” pseudotyped with a VSV-G envelope fusion protein comprising an anti-CD24 scFv. See e.g. Example 7. The specification as filed never discloses the use of an isolated lentiviral sub-particle such as a capsid. Therefore, the term lentivirus particle is being interpreted as an engineered lentiviral vector comprising the gene for integrase.
Claim Rejections - 35 USC § 112
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 57, 60-61, 66-67, 70-71 and 77-78 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. This is a new rejection necessitated by amendment.
Regarding claim 57, the claim recites:
…wherein the cancer is associated with cancer cells expressing human cluster of differentiation 24 (CD24),... It is not clear what it means for a cancer to be associated with a particular type of cell, specifically to be associated with the CD24 marker. The specification does not define what it means to be associated with and the art recognizes CD24 to be a very common surface marker expressed on many normal cells and overexpressed in some cancers. Therefore, there is a question or doubt as to how the artisan may determine what a suitable target population for instant method is.
Claims 60-61, 66-67, 70-71 and 77-78 are rejected for depending from claim 57 and not remedying the indefiniteness.
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.
New Written Description
Claims 57, 61, 66, 70-71 and 77-83 are rejected under 35 U.S.C. § 112(a), as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention.
The crux of the statutory requirement governing written description is whether one skilled in the art, familiar with the practice of the art at the time of the filing date, could reasonably have found the later claimed invention in the specification as filed. Moreover, the courts have stated that the evaluation of written description is highly fact-specific, and that broadly articulated rules are inappropriate. It is also important to remember that the true issue in question is not whether the specification enables one of ordinary skill in the art to make the later claimed invention, but whether or not the disclosure is sufficiently clear that those skilled in the art will conclude that the applicant made the invention having the specific claim limitations.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP 2163.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . .").
Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398”.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claims the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitutes a sufficient number of representatives, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
For written description, the analysis (a) considers actual reduction to practice, (b) disclosure of drawing or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed and (d) Representative number of examples.
Scope of the Invention
Claim 57 is drawn to a method of treating cancer or targeting a population of cancerous cells overexpressing CD24 by a) administration of a lentivirus comprising (i) a linear molecule of single-stranded RNA comprising long terminal repeat (LTR) sequences (ii) an integrase and (iii) a CD24 antibody or an antigen-binding molecule, and b) administration of at least one integration-promoting agent to a subject, and any combination thereof. Independent claim further limits the integration-promoting agent to one of three peptides.
Dependent claim 66 limits the integrase to an integrase enzyme selected from the group consisting of HIV-1 integrase, HIV-2 integrase, an active fragment thereof, and an active analog thereof and new claims 79-80 limit the integrase to that of HIV.
The MPEP states that a broad genus can be described by a showing of representative number of examples. The claims in the instant application are broad.
In the instant case, the genera are:
the LV particle comprising integrase (claim 57)
an integrase enzyme (claim 57) and an active fragment thereof, and an active analog thereof (claim 66);
any combination of integration-promoting agent (claims 57).
The broadest reasonable interpretation of the scope of these genera are a method of using any lentivirus that has been genetically modified to i) express a CD24 antibody or an antigen- binding fragment thereof comprising anti-CD24 scFv and ii) has an integrase or a modified integrase (an active fragment thereof, and an active analog thereof) and the method requires administration of at least one integration promoting agent.
(a) Actual reduction to practice/ (b) Disclosure of drawing or structural chemical formulas:
Species Disclosed
The originally filed disclosure teaches a variety of tumor cell lines were sensitive to a combination of infection with a lentiviral vector pseudotyped with an anti-CD24 scFv moiety and treatment with peptides derived from HIV-1 integrase (INS or INr2). To clarify, the latter peptides are integration-promoting agents and do not qualify as integrase. See examples 1-4 and 6. The results suggest that treatment with only the lentiviral vector provided little or no effect on H1975 lung cancer cells or BT549 breast cancer cells (Figs. 2B (see results for scrambled peptide) and 5D), and that the INR peptide appeared to be ineffective on BT549 breast cancer cells (Fig. 5D). The disclosure also teaches by way of an in vitro assay that a combination of HIV-1 integrase and a peptide derived from HIV-1 integrase (INS), results in increased integrase activity. See Fig. 5A. Thus, the species disclosed are:
integrase enzyme: HIV-1 integrase;
CD24 antibody and antigen-binding fragment thereof: anti-CD24 scFv;
integration-promoting agent: INS/INR/INr2.
Species Not Disclosed
1. The specification provides no working example of any embodiment of the invention where a i) an integrase other than HIV-1 integrase has been tested and ii) lentivirus comprises: an active fragment thereof, and an active analog thereof of a viral integrase. It is noted that isolated lentiviruses are known to naturally comprise integrase. However, they are not known to comprise just an active fragment thereof, and an active analog thereof. The specification does not shed any light on this confusion because the specification does not describe the making of the lentiviral vector. The working examples describes use of vectors with anti-CD24 antibody fragment (scFv): Humanized Anti-CD24 antibody fragment (scFv) was engineered and fused to the lentivirus envelope (Example 4), Lentivirus - Anti- 10 CD24 scFv fused to the VSV-G virus envelop - 30 MOI (Example 5), Lentivirus - Anti-CD24 scFv fused to the VSV-G virus envelop (Example 6). There is no other disclosure of an engineered virus.
2. The specification provides no results for INr1 peptide rather INR, and in some examples INr2 peptide, However the claims recite INr1, INr2 and INS, and any combination thereof of. The specification describes some experiments (Example 8 onwards) with a combination of INr2 and INS. However, no conclusion can be drawn from these because results obtained are neither shown nor discussed. Therefore, the description of these experiments is unnecessary.
(c) Sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties, functional characteristics when coupled with known or disclosed
The species that are described are not an adequate written description of the genus because there is no distinguishing features described except for function; i.e., there is no structural feature commonly possessed by the member of the genus that distinguishes them from others. Accordingly one of ordinary skill in the art cannot readily visualize or recognize the identity of the members of the genus. A genus can be described by means of reciting a representative number of species that fall within the scope of the genus or of a structural feature, which constitutes a substantial portion of the genus, that are common to the members of the genus.
In the instant case, the specification fails to adequately describe a structural feature common to the genera of:
LV particles comprising integrase; HIV-1 integrase is the sole species described therefore, it is assumed that the LV particle used in experiments is HIV;
an active fragment thereof, and an active analog thereof; HIV-1 integrase is the sole species described, not fragments or analogs thereof;
integration-promoting agent: INS/INR/INr2 peptides are the species described of which INR was ineffective; and only a combination of INS and INr is described.
Nor does the specification provide a reasonable number of examples that would reasonably convey to one of ordinary skill in the art the members of the genus.
It has been held by the courts that a small number of examples do not constitute a representation of a broad genus. Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618 (determining that the disclosure of two chemical compounds within a subgenus did not describe that subgenus); In re Grimme, 274 F.2d 949, 952, 124 USPQ 499, 501 (CCPA 1960) ("[I]t has been consistently held that the naming of one member of such a group is not, in itself, a proper basis for a claim to the entire group. However, it may not be necessary to enumerate a plurality of species if a genus is sufficiently identified in an application by 'other appropriate language.' ") (citations omitted). The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material. Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims.
(d) Representative number of examples
Some examples are discussed in (a) above. The specification also disclosed an experiment in which a xenotransplant mouse model comprising H1975 lung cancer cells was treated with two different doses (108 and 109 particles) of an undisclosed/undescribed lentivirus. The purpose of the experiment was to calibrate the in vivo amount of lentivirus particles for injection into a mouse tumor model, and there is no disclosure of the administration of any integrase-derived peptides in this experiment. In describing the results, the specification states that “Lentiviral therapy exhibited a reduction in tumor growth of approximately 50%.” See page 39, lines 17-18. The results in Fig. 7A show a delay in tumor growth as a result of treatment, but ultimately a greater rate of growth than the control rate in the animals receiving the higher dose. The relevance of this experiment to the claimed invention is unclear because it is unclear if the administered lentivirus produced the recited dsDNA comprising two LTRs. Moreover, the results are inconsistent with those of Fig. 2B in which treatment of H1975 cells with lentivirus and a scrambled peptide had little or no effect on cell survival.
Thus, the specification does not provide an adequate written description of any LV, fragment thereof/ active fragment thereof/ active analog/ any combination thereof of that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method. Further, the application fails to describe the second active step in the intended method; i.e., the combination of integration-promoting agents.
Since the specification fails to adequately describe a structural feature common to the genus, and does not provide a reasonable number of examples that would reasonably convey to one of ordinary skill in the art the members of the genus, the claimed invention lacks written description.
Examiner Suggestion: Amend lentivirus particle or integrase to a term that is described. Delete: 1. an active fragment thereof, and an active analog thereof and 2. any combination thereof.
Rewritten Scope of Enablement
Claims 57, 61, 66, 70-71 and 77-83 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 a method of treating an animal model of cancer by administering to the model a lentiviral vector, wherein the lentiviral vector is pseudotyped with an anti-CD24 scFv moiety, and a peptide of SEQ ID NO: 1 or 3, does not reasonably provide enablement for the treatment of cancer in a subject in need of such treatment, as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Nature of the Invention and Breadth of the Claims
Claims 57, 61, 66, 70-71 and 77-83 are drawn to the treatment of cancer by selectively destroying CD24 positive cancer cells by targeting to the cells a lentiviral particle comprising a linear single stranded RNA molecule comprising long terminal repeat sequences (LTRs) and an integrase capable of binding the LTRs, and further administering an integration-promoting agent. The claims are considered to be extremely broad because they place no limitation on the type of cancer to be treated.
Claim 57 is considered to be extremely broad in view of the fact that there are hundreds of types of cancers (see e.g. Tomlinson at https://info.isabelhealthcare.com/blog/how-many-types-of-cancer-are-there-world-cancer-day-2017) caused by thousands of different mutations (Lobo (2008) at https://www.nature.com/scitable/topicpage/chromosome-abnormalities-and-cancer-cytogenetics-879/). CD24 is expressed on many normal cells (The protein atlas, retrieved from the human protein atlas webpage on the internet <Tissue expression of CD24 - Summary - The Human Protein Atlas> 4 pages, [retrieved on 2nd April 2026]). CD24 overexpression is not diagnostic of most cancer cells (The protein atlas, retrieved from the human protein atlas webpage on the internet <https://www.proteinatlas.org/ENSG00000272398-CD24/cancer> 3 pages, [retrieved on 1st April 2026]).
Claim 77 limits the cancer to pancreatic or lung cancer.
State of the Art and Level of Unpredictability
Treatment of Cancer
At the time of the invention: i) there is a lack of knowledge on treating a disease by targeting a marker that is expressed on both normal and diseased cells; and ii) there was considerable unpredictability in translating the results obtained in cell culture and xenograft models of cancer to treatment of actual disease, as discussed further below. Further, CD24 is not prognostic in Pancreatic Adenocarcinoma (The protein atlas, retrieved from the human protein atlas webpage on the internet < https://www.proteinatlas.org/ENSG00000272398-CD24/cancer/pancreatic+cancer> 1 page, [retrieved on 1st April 2026]).
Mak et al (Am J Transl Res 2014;6(2):114-118) taught that although animal models play a large role in the evaluation of efficacy and safety of new cancer interventions, genetic, molecular, and physiological limitations often hinder their utility. Despite successful pre-clinical testing, 85% of early clinical trials for novel drugs fail; of those that survive through to phase III, only half become approved for clinical use. Thus the average rate of successful translation from animal models to clinical cancer trials is less than 8%. Furthermore, fewer than one in five cancer clinical trials find their way to the peer-reviewed literature, generally due to negative findings. See abstract and paragraph bridging columns on page 114.
Morgan (Mol. Ther. 20(5): 882-884, 2012) taught that differences in the biology of mice and humans provide restrictions on the utility of tumor xenograft models, e.g. mice are significantly smaller, have a much higher metabolic rate, are inbred, and have a short life span. In addition, whereas most human tumors take years to grow, tumor xenografts are transplantable tumors designed to grow to treatment size in weeks, not years, and so are not representative of the typical disease. Morgan indicated that the tumor line chosen to be transplanted is probably one of the most significant reasons for failure of xenotransplantation data to be translated to human clinical results. Monogenic human tumor cell lines are almost exclusively used, and it is now well established that tumor cell lines can bear little resemblance to primary cancers. For example, in glioblastoma detailed analysis of genomic stability and gene expression changes revealed considerable differences when primary tumors were compared with established cell lines. See paragraph bridging pages 882 and 883, and first paragraph on page 883.
Similarly, Day et al (Cell 163: 39-53, 2015) taught that cancer is typified by enormous disease complexities that challenge clinical success. Such challenges include tumor microenvironment complexities, intra- and inter-tumor molecular and biological heterogeneity, systemic and tumoral immune and metabolic response heterogeneity, and the ability of drug-resistant stem-like cancer-initiating cells to repopulate treated cancers. See first two sentences on page 39. Day indicated that cell line-derived mouse xenograft models are easily established in a wide variety of laboratory settings and have been successfully used to identify an abundance of cytotoxic drugs leading to chemotherapy treatments. However, successful development of effective drugs identified in such models is actually rare, as evidenced by low FDA approval rates of drugs emerging from such studies. The fact that most cancer therapeutics fail in clinical phase II and Ill efficacy assessment indicates that these models inadequately address complex challenges to successful treatment, such as cancer heterogeneity and drug resistance. Consequently, cell line-derived mouse xenograft models cannot be used to optimize a multitude of variables known to influence therapeutic outcomes such as drug delivery methods and variable dosing. As a result, their value lies in identifying non-targeted cytotoxic agents, primary assessment of drug toxicity, analyzing resistance mechanisms, and in triaging potentially effective targeted therapies for evaluation in more representative models. See paragraphs bridging columns on page 41. Therefore, while xenograft models provide a first step in evaluating potential drugs, they do not provide evidence that is reliably predictive of therapeutic success.
Horvath et al (Nature Reviews Drug Discovery 15:751-769, 11-2016) reviewed the state of the art of cell-based disease models and indicated that "[t]he common and persistent failures to translate promising preclinical drug candidates into clinical success highlight the limited effectiveness of disease models currently in use in drug discovery" (see abstract). Horvath indicated that, in the field of cancer, poor clinical translation can largely be attributed to the failure of disease models to recapitulate key pathophysiological features of the human disease, including complex inter- and intratumor heterogeneity, poor drug penetration through tissue, host-stroma-tumor cell interactions, and the cancer stem cell niche, all of which may have profound effects on the therapeutic response in vivo (page 752, center column). Most cell-based assay screens use transformed or immortalized cell lines that have been cultured for many generations, resulting in a substantial drift in their genetic, epigenetic and physiological characteristics, which means they are not a good model of primary tissue cells. The gross genetic and epigenetic abnormalities (characterized by multiple genetic rearrangements and amplified gene copy numbers) associated with long-term culture confound pharmacogenomic and functional genomic studies. Genetic adaptation resulting from long-term in vitro cultures also contributes to heterogeneity in cultures of the same cell line between passages, batches and laboratories (page 752, second paragraph). In vitro cell culture conditions poorly recapitulate the distinct microenvironments that define normal and diseased tissue phenotypes. This has a profound impact on cell metabolism, reactive oxygen species (ROS) production, mitochondrial functions and, ultimately, the differentiation and function of cells. Conventional tissue culture systems do not readily permit the formation of short-range gradients of nutrients, hormones and oxygen that are often experienced by cells, depending on the distance to the nearest blood vessel (paragraph bridging pages 752 and 753).
It was also unclear that infection of a given disease tissue by a lentiviral vector was sufficient to cause adequate cell death to result in the treatment of disease. See e.g. Wenger et al (Cancer Gene Therapy (2007) 14, 316–326). Wenger disclosed a method in which a lentiviral vector encoding TRAIL was used to induce apoptosis in cultured cell lines and to delay tumor progression in a xenograft animal model of non-small cell lung cancer, however, lentiviruses lacking any cytotoxic payload (i.e. GFP substituted for TRAIL) provided no therapeutic effect. See abstract, Fig. 1 on page 318, and Fig. 4 on page 321.
Given the state of the art in use of cancer cell lines and cell line-derived tumor xenograft models, one of skill would recognize that the data provided in such models is usually not predictive of success in treatment, but instead only provides a first step in the evaluation/development process for new drugs.
Guidance and Examples Provided in the Specification.
This section is a repetition of the similarly titled section in the Written Description rejection. The specification demonstrates that variety of tumor cell lines were sensitive to a combination of infection with a lentiviral vector pseudotyped with an anti-CD24 scFv moiety and treatment with peptides derived from HIV-1 integrase (INS or INr2). See examples 1-4 and 6. The results suggest that treatment with only the lentiviral vector provided little or no effect on H1975 lung cancer cells or BT549 breast cancer cells (Figs. 2B (see results for scrambled peptide) and 5D), and that the INR peptide appeared to be ineffective on BT549 breast cancer cells (Fig. 5D). The specification provides no working example of any embodiment of the invention where a lentiviral particle comprising a viral integrase fragment or analog thereof is delivered to a cell by any means other than by lentiviral transduction. It must be noted that the nature of the lentiviruses in the examples is not fully disclosed, and it is not clear if these lentiviruses comprised integrase, integrase fragment or analog thereof Thus it is unclear if the lentiviruses used in the examples are representative of claim embodiments in which a lentiviral particle comprising integrase is targeted to a cell (by any means other than undergoing the conventional lentiviral life cycle).
The specification also disclosed an experiment in which a xenotransplant mouse model comprising H1975 lung cancer cells was treated with two different doses (108 and 109 particles) of an undisclosed/undescribed lentivirus. The purpose of the experiment was to calibrate the in vivo amount of lentivirus particles for injection into a mouse tumor model, and there is no disclosure of the administration of any integrase-derived peptides in this experiment. In describing the results, the specification states that “Lentiviral therapy exhibited a reduction in tumor growth of approximately 50%.” See page 39, lines 17-18. The results in Fig. 7A show a delay in tumor growth as a result of treatment, but ultimately a greater rate of growth than the control rate in the animals receiving the higher dose. The relevance of this experiment to the claimed invention is unclear because it is unclear if the administered lentivirus either comprised integrase or fragment or analog thereof. Moreover, the results are inconsistent with those of Fig. 2B in which treatment of H1975 cells with lentivirus and a scrambled peptide had little or no effect on cell survival.
In summary, at best, the specification may provide a working example of the treatment of a xenograft animal model of cancer, wherein the recited but not fully defined LV is administered. However, it is not clear that this is the case. The specification does not clearly provide adequate guidance that would necessarily result in the delivery of sufficient complexes of LV with integrase to induce cell death in any specifically targeted cell in any disease or condition. A further assumption being made by the Examiner here is that the undisclosed virus used in Example 8 is the same as that used for the in vitro treatment of Example 6.
Finding of a Requirement for Undue Experimentation
In view of the breadth of the claims, which embrace the treatment of cancer with a targeting molecule that is not specific to cancer, the state of the art and unpredictability in the art with regard to treating cancer, the failure to disclose any working example of the treatment of any actual disease or condition, and the failure to provide guidance that would adequately prepare one of skill to address the unpredictability in the art as outlined above, one of skill would have to perform undue experimentation to use the invention as claimed.
Response to Arguments
Applicant's arguments filed 07/10/2025 have been fully considered but they are not persuasive.
112a Scope of Enablement
Applicant addresses the 112a Scope of Enablement made in previous Final Office Action at pages 4 - 5 of the response. Applicant notes that the claims have been limited to recite specific populations of CD24 expressing cancer cells.
This is not persuasive because CD24 expressing cancer cells is still a grouping of a vast number of very heterogeneous cells. The dependent claims limit the cancer to breast and pancreatic cancer. However, the TCGA compendium of cancer markers discloses that CD24 is not prognostic in pancreatic cancer. These issues have been addressed in the Scope of Enablement rejection. Therefore, the scope of the claims is still broad and Applicants have not addressed the unpredictability in targeting such a vast grouping of cells.
Applicant then asserts that the procedures, compositions and methods described in the application, were found to be effective in animal models which closely resemble conditions in humans. Applicant refers to Shapira et al., (Oncogene (2021) 40:3 815-3825), as they did in the previous set of Remarks, which indicates that integrase-derived peptides administered together with CD24-targeted lentiviral particles inhibit the growth of CD24 expressing cancer cells.
The Examiner has reviewed this reference. As indicated in Examiner’s response to Remarks in the Final Office Action dated 01/13/2025, it is unclear from the text of the cited reference of Shapira et al., how the experiments were actually performed. Specifically, it is unclear if the cells were administered a lentivirus comprising the elements of claim 57. On the one hand the abstract states “Lentivirus particles, containing non-functional DNA led to massive cell death (40–70%)”, implying that the lentiviral particles used in the experiment contained just a capsid. On the other hand, the reference indicates that lentiviral particles comprising dsDNA were generated using standard packaging constructs that would appear to lead to normal RNA-containing lentiviral virions (see first paragraph on page 10 and Supplemental Figure S1). Simply put, it is not clear if the lentiviral particle in the reference cited by Applicant in the Remarks is the same as the LV used in instant application.
In any event, the rejection of record addresses the unpredictability in extending the results obtained in xenograft animal models to those that might be obtained in the treatment of actual disease. The response filed 07/10/2025 does not address these issues. For these reasons the Scope of Enablement rejection is maintained.
112a Written Description
Applicants have not addressed the Written Description rejection made in the NFOA. The amendments made have overcome the previous Written Description rejection. However, a rewritten Written Description rejection addressing amendments has been made in this Office Action because, “Every patent must describe an invention. It is part of the quid pro quo of a patent; one describes an invention, and, if the law's other requirements are met, one obtains a patent.” (emphasis added). See Araid Pharmaceuticals Inc. v. Eli Lilly & Co. 593 F3d 1336, 94 USPQ2d 1161 (Fed. Cir. 2010).
“Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed… Application of the
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requirement, however, is not subsumed by the “possession” inquiry. A showing of “possession” is ancillary to the statutory mandate that “[t]he specification shall contain a written description
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of the invention,” and that requirement is not met if, despite a showing of possession, when the specification does not adequately describe the claimed invention.” (emphasis added). See Enzo Biochem Inc. v. Gen-Probe Inc. 323 F3d 956, 63 USPQ2d 1609 (Fed. Cir. 2002).
The specification does not allow one skilled in the art to recognize that any LV could be used, the integrase could be substituted with an active fragment thereof, or an active analog thereof, amongst other limitations, or any combination of integration-promoting agents could be used. Hence, even if applicant was in possession of lentivirus used to infect cells as of the filing date sought, the written description requirement is not met because the specification does not adequately describe the claimed invention, which claims a lentivirus used to infect cells creates sufficient dsDNA breaks in the host cell to cause the destruction of the cell.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
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SHABANA S. MEYERING, Ph.D.
Examiner
Art Unit 1635
/SHABANA S MEYERING/Examiner, Art Unit 1635
/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635