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 with traverse of Species A (i.e., a single and specific neurodegenerative event as a non-traumatic brain injury caused by an ischemic stroke); and Species B (i.e., a single and specific protein as wild-type human transferrin (SEQ ID NO: 1)) in the reply filed on October 9, 2025, is acknowledged.
Regarding Species A, the traversal is on the grounds with respect to cerebral anoxia and cerebral hypoxia because there is no prior art cited to establish that the generic claim does not avoid the prior art (See Applicant’s response received on 10/9/25, pg. 5). Applicant asserts that ischemic stroke, cerebral anoxia and cerebral hypoxia are all of a similar nature as they each represent a different manifestation of the same underlying pathophysiological process; namely, oxygen deprivation in the brain (See Applicant’s response received on 10/9/25, pg. 5). Thus, these three species of neurodegenerative events should all be examined together (See Applicant’s response received on 10/9/25, pg. 6).
This is not found persuasive because cerebral anoxia and cerebral hypoxia may all involve lack of oxygen to the brain, but they do not per se derive from similar pathophysiological conditions and/or mechanisms. Rather, ischemic stroke is a species of cerebral anoxia/hypoxia. Cerebral anoxia/hypoxia does not have to result from an ischemic stroke. Synapse teaches that anoxic and hypoxic brain injury can be caused by several unrelated conditions including near drowning, drug overdose, strangulation, severe asthma, CO inhalation, and stroke (See Synapse, “Anoxic and Hypoxic Brain Injury”, available online at https://synapse.org.au/fact-sheet/anoxic-and-hypoxic-brain-injury-lack-of-oxygen/, 3 pages (accessed on 1/28/26; first available 2019). Therefore, contrary to Applicant’s argument, examination or cerebral anoxia or hypoxia does not per se correlate to examination of ischemic stroke.
Regarding Species B, the traversal is on the grounds that the alternatives in the Markush group of proteins, i.e., lactoferrin and transferrin, are of a similar nature in that they share a common structure and belong to a recognized class of chemical compounds in the art to which the invention pertains (See Applicant’s response received on 10/9/25, pg. 5). Both protein have the common activity of inducing generation of new neural cells as recited in instant claim 1, and Baker et al. teaches that the two proteins share many structural and functional features including the ability to bind iron very tightly, but reversibly, with a highly-conserved three-dimensional structure and essentially identical iron-binding sites (See Applicant’s response received on 10/9/25, pg. 6; Baker, abstract). Thus, all forms of lactoferrin and transferrin represent alternatives that are of a similar nature such that they have unity of invention (See Applicant’s response received on 10/9/25, pg. 6-7).
This is not found persuasive because the claimed Markush group is not limited to wild-type lactoferrin and transferrin. As will be further articulated in the 112(a), written description, rejection below, the scope of the claimed Markush group encompasses mutants, fragments, derivatives, variants of each wild-type protein (See instant, pg. 4, last paragraph to pg. 5, 1st paragraph; pg. 6, last paragraph to pg. 7, 1st and 3rd paragraph). These modified proteins do not share a significant structural element given that there is no indication in the specification or art of a core sequence/residues that is necessary for each species to exhibit the function of the wild-type proteins. As such, contrary Applicant’s argument, the claimed Markush alternatives do not satisfy (B)(1). Similarly, given the enormous structural scope of the Markush alternatives, e.g., a fragment with a single deleted residue to any dipeptide, a mutant/variant with any number of substitutions, there is no indication that all the alternatives have a common property, even the claimed use inducing generation of new neural cells. As such, contrary to Applicant’s argument, the claimed Markush alternatives do not per se satisfy (A). Thus, Species B lacks unity of invention.
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s election without traverse of Species C (i.e., a single and specific serum or plasma protein as alpha-1 antitrypsin) in the reply filed on October 9, 2025, is acknowledged.
Please note that in light of the Examiner’s search, Species C is expanded to include tissue plasminogen activator (tPa).
Status of Claims
Claims 1-42 were originally filed on January 4, 2023.
The amendment received on January 10, 2023, canceled claims 11-21 and 32-42; and amended claims 1-10 and 23-31. The amendment received on October 9, 2025, amended claim 30; and added new claim 43.
Claims 1-10, 22-31, and 43 are currently pending and claims 1-4, 8-10, 22-25, 29-31, and 43 are under consideration as claims 5-7 and 26-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on October 9, 2025.
Priority
The present application claims status as a 371 (National Stage) of PCT/EP2021/068800 filed July 7, 2021, and claims priority under 119(e) to U.S. Provisional Application No. 63/049,516 filed on July 8, 2020.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on January 4, 2023; July 23, 2024; and September 24, 2025, are being considered by the examiner.
Claim Interpretation
For purposes of applying prior art, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation set forth below, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
For claims 1 and 22, with respect to the protein to be administered, it is noted that the instant specification defines transferrin and lactoferrin similarly as including a mammalian wild-type transferrin/lactoferrin protein, a functional mutant thereof, a functional fragment thereof or combinations thereof (See instant, pg. 4, last paragraph to pg. 5, 1st paragraph; pg. 6, last paragraph to pg. 7, 1st paragraph). Furthermore, the specification teaches that the terms transferrin and lactoferrin include within their scope recombinant derivatives that differ from the wild type amino acid sequences of the human proteins, i.e., SEQ ID NOs: 1 and 2, respectively, by one or more substitutions, one or more deletions, or one or more insertions that may not materially alter the structure, or hydropathic nature of the recombinant proteins relative to the wild type proteins (See instant, pg. 7, 3rd paragraph). Recombinant variants of transferrin and lactoferrin within the scope of the present invention can additionally comprise at least one post-translation modification such as pegylation, glycosylation, polysialylation or combinations thereof (See instant, pg. 7, 3rd paragraph). Thus, the claimed protein encompasses a vast array of protein/peptide amino acid sequences including the wild-type sequences and mutants/variants/fragments/derivatives thereof that are required to maintain the functionality of the wild-type sequences.
For claims 1 and 22, with respect to “neural cells”, it is noted that the instant specification defines neural cells as including all cells of the nervous system (See instant, pg. 11, 1st paragraph).
For claim 1, with respect to “neurodegenerative event”, it is noted that the instant specification defines the term as an event that causes the loss of structure and/or function of neural cells and includes the death of neural cells (See instant, pg. 11, 2nd paragraph). The scope of claim 1 limits the neurodegenerative event to one of a traumatic brain injury (TBI), a non-traumatic brain injury (NTBI), a spinal cord injury, a peripheral nerve injury, or peripheral neuropathy. NTBI (elected by Applicants) is defined as an injury to the brain resulting from a non-traumatic cause (See instant, pg. 11, 5th paragraph). Examples include tumors, strokes, transient ischemic attacks, brain hemorrhages, toxins/drugs, cerebral hypoxia, cerebral anoxia, hydrocephalus, meningitis, and encephalitis (See instant, pg. 11, 5th paragraph). However, the scope of claim 1 encompass promoting and/or inducing generation of new neural cells (i.e., any cells of the nervous system) in a patient that has suffered an injury to the brain resulting from any non-traumatic cause. Note: that Applicant elected an ischemic stroke as the NTBI cause. Thus, examination of claim 1 is limited to promoting and/or inducing generation of new neural cells in a patient that has suffered an ischemic stroke.
For claim 22, with respect to “stimulating neural cell development”, it is noted that the instant specification defines this phrase such that the transferrin or lactoferrin have a direct or indirect effect on neural progenitor cells and/or neural stem cells in the patient so as to produce new neural cells (See instant, pg. 11, last paragraph). Although not limited, the administration of transferrin or lactoferrin results in an increase in at least one of: (i) proliferation of the neural progenitor cells and/or neural stem cells within the patient or (ii) inducing differentiation of the neural progenitor cells and/or neural stem cells into differentiated neural cells, compared to neural progenitor cells/neural stem cells that have not been exposed to the protein (See instant, pg. 11, last paragraph). Similar to claim 1, the scope of claim 22 encompasses producing new neural cells (i.e., any cells of the nervous system) in a patient that has suffered an ischemic stroke.
Claim Rejections - 35 USC § 112
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 1-4, 8-10, 22-25, 29-31, and 43 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claims 1 and 22 include administering a therapeutically effective amount of a “protein selected from transferrin, lactoferrin and combinations thereof”. The interpretation of this phrase is described above in the “Claim Interpretation” section where transferrin and lactoferrin are defined as including a mammalian wild-type transferrin/lactoferrin protein, a mutant thereof, a fragment thereof or combinations thereof (See instant, pg. 4, last paragraph to pg. 5, 1st paragraph; pg. 6, last paragraph to pg. 7, 1st paragraph). Furthermore, the specification teaches that the terms transferrin and lactoferrin include within their scope recombinant derivatives that differ from the wild type amino acid sequences of the human proteins, i.e., SEQ ID NOs: 1 and 2, respectively, by one or more substitutions, one or more deletions, or one or more insertions that may not materially alter the structure, or hydropathic nature of the recombinant proteins relative to the wild type proteins (See instant, pg. 7, 3rd paragraph). Recombinant variants of transferrin and lactoferrin within the scope of the present invention can additionally comprise at least one post-translation modification such as pegylation, glycosylation, polysialylation or combinations thereof (See instant, pg. 7, 3rd paragraph). As such, the claimed protein encompasses a vast array of protein/peptide amino acid sequences including the wild-type sequences and mutants/variants/fragments/derivatives thereof without a common core sequence shared among the species that are required for mutants, variants, fragments, and/or derivatives of transferrin or lactoferrin to maintain the functionality of the wild-type sequences. For example, a wild-type transferrin amino acid sequence is depicted as instant SEQ ID NO: 1 with 679 total amino acid residues. As such, a fragment of SEQ ID NO: 1 encompasses any dipeptide (i.e., two contiguous amino acids) up to a peptide with a single deleted residue at the N- and/or C-terminus. Mutants and variants encompass any number of substitutions, deletions, and/or insertions. In addition to certain manipulations of transferrin or lactoferrin, the mutants, variants, fragments, and/or derivatives must also have the function of the wild-type transferrin or lactoferrin. Thus, the scope of the claimed proteins encompass an enormous array of mutants, variants, fragments and/or derivatives of transferrin or lactoferrin without a common core sequence necessary for each to function as the wild-type proteins.
The written description requirement may be met by provided a representative number of species of the genus and/or in light of the state of the art. With regard to the state of the art, Gasull Dalmau et al. US Publication No. 2014/0323409 A1 teaches “apo-transferrin” that is the fraction of transferrin that is free from iron (See ‘409, [0017]). “Holo-transferrin” is when the transferrin is saturated with iron (See ‘409, [0017]). However, the amino acid sequence of the transferrin remains unaltered, and is identical to the wild-type transferrin protein. Steere et al. teaches that the transport of iron throughout the body by human serum transferrin (hTF) (i.e., wild-type hTF) is central to iron homeostasis (See Steere et al., Biochem. 51:686-694 (2012) at pg. 2, 1st paragraph). The homologous N- and C-lobes of hTF are divided into two subdomains (N1 and N2, C1 and C2), that fold to form a deep cleft capable of binding a single ferric iron (See Steere, pg. 2, 1st paragraph). There are four unequally distributed species of hTF differing with regard to iron content found in plasma: diferric hTF, monoferric N-lobe hTF, monoferric C-lobe hTF, and apohTF (iron-free) (See Steere, pg. 2, 1st paragraph). The homodimeric transferrin receptor (TFR) preferentially binds diferric hTF at physiological pH, the two monoferric hTFs bind ~10 fold weaker, and the apohTF binds very weakly, if at all (See Steere, pg. 2, 2nd paragraph). Steere et al. teaches a recombinant non-glycosylated monoferric hTF that binds iron only in the N-lobe (Y426F/Y517F mutations prevent iron binding in C-lobe), and a monoferric hTF that binds iron only in the C-lobe (Y95F/Y188F mutations prevent iron binding in N-lobe) (See Steere, pg. 2, 1st paragraph, footnote 1). Moreover, Steere et al. found that residues R50 in the N1 subdomain and E664 in TFR, and residues D356 in the C1 subdomain and R651 in TFT interact through the formation of salt bridges (See Steere, pg. 3, 1st paragraph). Steere et al. sought to examine specific residues of the hTF, i.e., R50, E141 and K148 in the N-lobe, E333 in the bridge between the two lobes, and R352, D356, E357, E367, E385, K511, and E625 in the C-lobe, by mutating each to alanine to determine their effect on binding of both diferric hTF and apohTF with TFR (See Steere, pg. 3, 2nd paragraph; Tables 1-2). The D356A mutant did not compete at all with the biotinylated diferric hTF for binding to the TFR thereby demonstrating the importance of this residue in the interaction between hTF and TFR (See Steere, pg. 6, 1st paragraph), and a number of the other hTF mutations (i.e., R50A, R352A, E357A, E357A/E625A, E367A, K511A) significantly affected the ability of the mutant to compete with diferric hTF, while the remaining mutants (i.e., E141A, K148A, and E385A) were about half as effective as the control at binding to the TFR (See Steere, pg. 6, 1st paragraph). Steere et al. concluded that residue D356 stabilizes the iron-bound hTF/TFR complex, residue E367 mediates lobe-lobe communication in the diferric hTF/TFR complex, and residue K511 stabilizes the iron-bound C-lobe in the hTF/TFR complex (See Steere, pg. 8, 2nd paragraph; pg. 9, 2nd and last paragraph). As such, Steere et al. demonstrates that a single mutation in the N-lobe or C-lobe can have a significant effect of the functionality of a mutant, variant, fragment or derivative of transferrin. Although Steere et al. teaches a limited number of single mutants, which demonstrates essential residues, i.e., D356, E367, and K511, for hTF functionality, these single mutants do not constitute a representative number of species within the claimed genus, nor a significant core sequence that would correlate to functionality. Thus, the claims are directed to proteins with a certain function but no correlated sequence associated with that function. Without such sequence structure, the specification does not convey possession of the breadth of the claimed genus.
Alternatively, the written description requirement may be met by providing a representative number of species of the genus. In this, the specification teaches a limited number of examples of sequences meeting the claimed limitations. More specifically, the specification teaches transferrin mutants include: i) Y188F mutant N lobe as SEQ ID NO: 3; ii) Y95F/Y188F N lobe as SEQ ID NO: 4; and iii) Y426F/Y517F mutant C lobe as SEQ ID NO: 5 (See instant, pg. 8, 3rd paragraph). The specification also broadly teaches the recombinant variants of transferrin and lactoferrin can have one or more conservative substitutions relative to the wild-type proteins in SEQ ID NOs: 1 and 2 where a conservative substitution is one in which an amino acid is substituted for another amino acid that has similar properties such that one skilled in the art would expect the secondary structure and hydropathic nature of the polypeptide to be substantially unchanged (See instant, pg. 7, 4th paragraph). Moreover, the specification teaches that “apo-transferrin” and “apo-lactoferrin” mean the protein having an iron saturation of less than 1% whereas “holo-transferrin” and “holo-lactoferrin” mean the protein having an iron saturation of 99% or greater (See instant, pg. 5, 3rd paragraph; pg. 7, 2nd paragraph). There are no examples of fragments or derivatives of transferrin that exhibit the function of the wild-type transferrin. As such, the examples in the specification do not constitute a representative number of species that an ordinary skilled artisan could extend to the claimed genus as a whole. Thus, the examples in the specification are not sufficient for the skilled artisan to envisage other substitutions, deletions or insertions at the other residue sites which preserve function.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, what is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides which preserve the required function, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, claims 1-4, 8-10, 22-25, 29-31, and 43 do not meet the written description requirement.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-4, 8-10, 22-25, 29-31, and 43 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 promoting and/or inducing generation of new neural cells in a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke by administering to the patient a therapeutically effective amount of a wild-type transferrin having an iron saturation of less than about 20% including apo-transferrin, the Y188F mutant (SEQ ID NO: 3), and the Y95F/Y188F mutant (SEQ ID NO: 4); and
for stimulating neural cell development in a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke by administering to the patient a therapeutically effective amount of a wild-type transferrin having an iron saturation of less than about 20% including apo-transferrin, the Y188F mutant (SEQ ID NO: 3), and the Y95F/Y188F mutant (SEQ ID NO: 4),
does not reasonably provide enablement:
for promoting and/or inducing generation of new neural cells in a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke by administering to the patient a therapeutically effective amount of any other transferrin having an iron saturation of greater than about 20% including holo-transferrin, and any other mutants, fragments, derivatives of transferrin including the Y426F/Y517F mutant (SEQ ID NO: 5); and
for stimulating neural cell development in a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke by administering to the patient a therapeutically effective amount of any other transferrin having an iron saturation of greater than about 20% including holo-transferrin, and any other mutants, fragments, derivatives of transferrin including the Y426F/Y517F mutant (SEQ ID NO: 5).
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.
As stated in MPEP §2164.01(a), “there are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is ‘undue’.” These factors include, but are not limited to:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The level of skill in the art;
5. The level of predictability in the art;
6. The amount of direction provided by the inventor;
7. The presence or absence of working examples;
8. The quantity of experimentation necessary needed to make or use the invention based on the disclosure.
See In re Wands USPQ 2d 1400 (CAFC 1988).
The eight In re Wands factors are applied to Claims 1-4, 8-10, 22-25, 29-31, and 43 as follows:
The Breadth of the Claims and The Nature of the Invention
Although addressing that the patient has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke and where the patient can be treated by administering a therapeutically effective amount of a transferrin that promotes and/or induces the generation of new neural cells and/or stimulates neural cell development in the patient (See claims 1 and 22), the scope of the transferrins that can be administered includes an enormous array of proteins and polypeptides such as any mutant, variant, fragment or derivative of transferrin (hereinafter referred to collectively as “a transferrin”) and includes transferrins with any iron saturation percentage. As described in the “Claim Interpretation” section and 112(a), written description, rejection supra, transferrin is defined as including a mammalian wild-type transferrin protein, a mutant thereof, a fragment thereof or combinations thereof (See instant, pg. 4, last paragraph to pg. 5, 1st paragraph). Furthermore, the specification teaches that the term, transferrin, includes within their scope recombinant derivatives that differ from the wild type amino acid sequences of the human proteins, i.e., SEQ ID NOs: 1 and 2, respectively, by one or more substitutions, one or more deletions, or one or more insertions that may not materially alter the structure, or hydropathic nature of the recombinant proteins relative to the wild type proteins (See instant, pg. 7, 3rd paragraph). Recombinant variants of transferrin within the scope of the present invention can additionally comprise at least one post-translation modification such as pegylation, glycosylation, polysialylation or combinations thereof (See instant, pg. 7, 3rd paragraph). As such, the claimed protein encompasses a vast array of protein/peptide amino acid sequences including the wild-type sequences and mutants/variants/fragments/derivatives thereof without a common core sequence shared among the species that are required for mutants, variants, fragments, and/or derivatives of transferrin or lactoferrin to maintain the functionality of the wild-type sequences. For example, the wild-type transferrin amino acid sequence is depicted as instant SEQ ID NO: 1 with 679 total amino acid residues. As such, a fragment of SEQ ID NO: 1 encompasses any dipeptide (i.e., two contiguous amino acids) up to a peptide with a single deleted residue at the N- and/or C-terminus. Mutants and variants encompass any number of substitutions, deletions, and/or insertions. Thus, the scope of the claimed administered proteins encompass an enormous array of mutants, variants, fragments and/or derivatives of transferrin in order to promote and/or induce generation of new neural cells and/or stimulate neural cell development in a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke. Accordingly, claims 1-4, 8-10, 22-25, 29-31, and 43 are unduly broad with respect to the scope of transferrins to be administered.
The State of the Prior Art
The prior art demonstrates that apo-transferrin that is iron-free treats an ischemic stroke in a subject by reducing damages such as the reduction in the volume of cortical infarction due to reperfusion or cerebral ischemia (See ‘409, [0024]-[0025], [0078]; Figures 1-2). ‘409 also demonstrated that the administration of apo-transferrin resulted in tested animals showed less neurological deficit and performed motor tasks involving the affected brain area with greater efficacy (See ‘409, [0079]; Figure 3). Contrary to apo-transferrin, holo-transferrin that is fully saturated with iron induced neuronal death and produced free radicals when administered to test animals (See ‘409, [0081]; Figure 4). Thus, ‘409 demonstrates that wild-type transferrin could only treat ischemic stroke in a subject when the transferrin had no iron saturation.
The Level of Skill in the Art
Practitioners in this art (medical clinicians, pharmacists, doctors and/or pharmaceutical chemists) would presumably be highly skilled in the art for promoting and/or inducing generation of new neural cells and/or stimulating neural cell development in a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke by administering a therapeutically effective amount of a transferrin.
The Level of Predictability in the Art
The instant claimed invention is highly unpredictable. If one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains (i.e., administering a therapeutically effective amount of a transferrin to a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke in order to promote and/or induce generation of new neural cells and/or stimulate neural cell development in the patient), then there is a lack of predictability in the art. Moreover, it is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. The court has indicated that the more unpredictable an area is the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). This is because it is not obvious from the disclosure of one species, what other species will work.
In the instant case, Applicants demonstrate that apo-transferrin (i.e., human amino acid sequence is wild-type of SEQ ID NO: 1) having an iron saturation less than 1%, SEQ ID NO: 1 having an iron saturation of 20% or less, and a Y188F mutant of SEQ ID NO: 1 having an iron saturation of less than 1% induced neuronal cell differentiation and neurogenesis in an in vitro neuroblastoma cell line that serves as a model for neurodegenerative disorders (See instant, Examples 1-4 and 6; Figures 1, 3-4, and 6), but also demonstrates that holo-transferrin (i.e., amino acid sequence is wild-type of SEQ ID NO: 1) having an iron saturation of 100%, and SEQ ID NO: 1 having an iron saturation of 30% or more failed to induce neuronal cell differentiation and neurogenesis in the in vitro neuroblastoma cell line (See instant, Examples 4 and 6; Figures 4A and 6B). Moreover, Applicants fail to demonstrate any transferrin mutants, variants, fragments or derivatives other than a Y188F mutant of SEQ ID NO: 1 having an iron saturation of less than 1% that induced neuronal cell differentiation and neurogenesis in vitro or in vivo. In fact, the specification demonstrates that SEQ ID NO: 1 that has an iron saturation of at least 30% failed to induce neuronal cell differentiation and neurogenesis in the in vitro neuroblastoma cell line (See instant, Example 6; Figure 6B).
Thus, Applicants appear to rely on the assumption that by providing evidence that apo-transferrin (i.e., human amino acid sequence is wild-type of SEQ ID NO: 1) having an iron saturation less than 1%, SEQ ID NO: 1 having an iron saturation of 20% or less, and a Y188F mutant of SEQ ID NO: 1 having an iron saturation of less than 1% induced neuronal cell differentiation and neurogenesis in an in vitro neuroblastoma cell line would exhibit similar intended results by administering the claimed genus of transferrins. However, such an assumption cannot be made because there is no indication that any transferrin fragments or derivatives would exhibit similar positive results for inducing neuronal cell differentiation and neurogenesis in vitro or in vivo. Similarly, a single transferrin mutant (i.e., SEQ ID NO: 3) does not constitute a representative number of transferrin mutants/variants that an ordinary skilled artisan can extrapolate the positive results of the one species to extend to other transferrin mutants/variants. Without more experimentation demonstrating the efficacy of a representative number of transferrins for inducing neuronal cell differentiation and neurogenesis in vitro and/or in vivo in a patient that has suffered a neurodegenerative even arising from a NTBI caused by an ischemic stroke, the level of unpredictability remains high. Therefore, it is unpredictable that administration of a therapeutically effective amount of a transferrin will induce neuronal cell differentiation and neurogenesis in vitro or in vivo in a patient that has suffered a neurodegenerative even arising from a NTBI caused by an ischemic stroke
The Amount of Direction Provided by the Inventor,
The Presence or Absence of Working Examples, and
The Quantity of Experimentation Necessary
In light of the unpredictability surrounding the claimed subject matter, the undue breadth of the claimed invention’s intended use, and the lack of adequate guidance, one wishing to practice the presently claimed invention would be unable to do so without engaging in undue experimentation. One wishing to practice the presently claimed invention would have to produce additional data and experimentation to determine whether administering a therapeutically effective amount of a transferrin to a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke would promote and/or induce generation of new neural cells and/or stimulate neural cell development in the patient.
The Specification discloses examples demonstrating that apo-transferrin (i.e., human amino acid sequence is wild-type of SEQ ID NO: 1) having an iron saturation less than 1%, SEQ ID NO: 1 having an iron saturation of 20% or less, and a Y188F mutant of SEQ ID NO: 1 having an iron saturation of less than 1% induced neuronal cell differentiation and neurogenesis in an in vitro neuroblastoma cell line that serves as a model for neurodegenerative disorders (See instant, Examples 1-4 and 6; Figures 1, 3-4, and 6). However, the Specification provides little specific guidance or direction on the methods of administering transferrin fragments, derivatives, or mutants/variants other than one mutant sequence (i.e., SEQ ID NO: 3) for promoting and/or inducing generation of new neural cells and/or stimulating neural cell development in a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke. The Specification even demonstrates that wild-type transferrin that has an iron saturation of at least 30% failed to promote and/or induce generation of new neural cells and/or stimulate neural cell development in vitro (See instant, Example 6). Applicants provide no data, examples, figures, etc. demonstrating the efficacy of a representative number of transferrins (i.e., mutants, variants, fragments and/or derivatives) for promoting and/or inducing generation of new neural cells and/or stimulating neural cell development in a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke that an ordinary skilled artisan can extrapolate from to extend to the scope of the claimed genus of transferrins. In the absence of such information, a person of ordinary skill in the art would reasonably require an undue quantity of experimentation to determine efficacy of a representative number of the claimed genus of transferrins for promoting and/or inducing generation of new neural cells and/or stimulating neural cell development in a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke.
Conclusion of 35 U.S.C. 112(a) (Enablement) Analysis
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claims 1-4, 8-10, 22-25, 29-31, and 43, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in claims 1-4, 8-10, 22-25, 29-31, and 43 would not be enabled by the written disclosure excluding that of administering a therapeutically effective amount of a wild-type transferrin having an iron saturation of less than about 20% including apo-transferrin, the Y188F mutant (SEQ ID NO: 3), and the Y95F/Y188F mutant (SEQ ID NO: 4) to a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke to promote and/or induce generation of new neural cells and/or stimulate neural cell development in the patient.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4, 8-9, 22-25, 29, and 43 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gasull Dalmau et al. US Publication No. 2014/0323409 A1 published on October 30, 2014 (hereinafter referred to as ‘409), alone or as evidenced by, Patel P, Bollu PC. Tissue Plasminogen Activator Therapy. [Updated 2025 Aug 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482376/.
For claims 1-2, 8-9, 22-23, and 29-30, ‘409 claims a method of treatment of brain ischemic stroke by administering apo-transferrin to an animal in need thereof (See ‘409, claim 1) where the apo-transferrin is administered in a dose between 1 and 1000 mg/kg weight (See ‘409, claim 12). ‘409 defines apo-transferrin as the fraction of transferrin that is free from iron (See ‘409, [0017]). As such, ‘409’s claimed method satisfies administering a therapeutically effective amount of the instant transferrin to a patient suffering from a neurodegenerative event arising from a NTBI such as an ischemic stroke as recited in claims 1, 8-9, 22, and 29-30 where the therapeutically effective amount of transferrin administered to the patient has an iron saturation of less than about 20%, i.e., iron-free, as recited in claims 2 and 23.
Regarding promoting and/or inducing generation of new neural cells as recited in claim 1 and stimulating neural cell development as recited in claim 22, ‘409 expressly claims treatment of the same patient population, i.e., a patient that suffered a neurodegenerative event arising from a NTBI such as an ischemic stroke, by performing the same manipulative step, i.e., administering a therapeutically effective amount of a transferrin to the patient, the result oriented effect of promoting and/or inducing generation of neural cells as recited in claim 1 or stimulating neural cell development as recited in claim 22 would necessarily and inherently occur as a result of practicing the method of ‘409. Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). Therefore, the ‘409 disclosure satisfies the claim limitations as recited in instant claims 1-2, 8-9, 22-23, and 29-30.
For claims 3 and 24, ‘409 discloses that the apo-transferrin for its use in the present invention is preferably human apo-transferrin (See ‘409, [0017], [0041]). Pursuant to MPEP 2131.02, it states that, “[i]f one of ordinary skill in the art is able to "at once envisage" the specific compound within the generic chemical formula, the compound is anticipated. One of ordinary skill in the art must be able to draw the structural formula or write the name of each of the compounds included in the generic formula before any of the compounds can be "at once envisaged." One may look to the preferred embodiments to determine which compounds can be anticipated.” In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962). In the instant case, given the limited types of apo-transferrin, i.e., human, an ordinary skilled artisan can at once envisage that the administered apo-transferrin is human apo-transferrin. Therefore, the ‘409 disclosure satisfies the claim limitations as recited in instant claims 3 and 24.
For claims 4 and 25, ‘409 discloses that the apo-transferrin can be prepared by methods known in the state of the art (See ‘409, [0041]). Moreover, ‘409 discloses that the apo-transferrin is in a recombinant form (See ‘409, [0041]). Pursuant to MPEP 2131.02, it states that, “[i]f one of ordinary skill in the art is able to "at once envisage" the specific compound within the generic chemical formula, the compound is anticipated. One of ordinary skill in the art must be able to draw the structural formula or write the name of each of the compounds included in the generic formula before any of the compounds can be "at once envisaged." One may look to the preferred embodiments to determine which compounds can be anticipated.” In re Petering, 301 F.2d 676, 133 USPQ 275 (CCPA 1962). In the instant case, given the limited potential sources of apo-transferrin, an ordinary skilled artisan can at once envisage that the administered apo-transferrin is recombinant. Therefore, the ‘409 disclosure satisfies the claim limitations as recited in instant claims 4 and 25.
For claim 43, ‘409 claims where the administering of apo-transferrin is in combination with an agent selected from a thrombolytic agent, a chelating agent, citicoline, fluoxetine, and lactoferrin where a human tissue plasminogen activator (tPa) (note: a plasma-based protein involved in converting plasminogen into plasmin as evidenced by Patel at pg. 2, 1st paragraph) is specifically claimed as a thrombolytic agent (See ‘409, claims 5-7). Therefore, the ‘409 disclosure satisfies the claim limitation as recited in instant claim 43.
Accordingly, the ‘409 disclosure anticipates instant claims 1-4, 8-9, 22-25, 29, and 43.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
103 - KSR Examples of 'Rationales' Supporting a Conclusion of Obviousness(Consistent with the "Functional Approach" of Graham)
Further regarding 35 USC 103(a) rejections, the Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) (KSR) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
Also, a reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
Claims 1, 10, 22, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Gasull Dalmau et al. US Publication No. 2014/0323409 A1 published on October 30, 2014 (hereinafter referred to as ‘409), alone or as evidenced by, Patel P, Bollu PC. Tissue Plasminogen Activator Therapy. [Updated 2025 Aug 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482376/, as applied to claims 1 and 22 above, and further in view of Moldthan et al., J. Stroke Cerebrovasc. Dis. 23:e355-e363 (2014), as applied to claims 10 and 31 herewith.
For claims 1 and 22, please see discussion of ‘409 and Patel et al. supra.
For claims 10 and 31, ‘409 teaches that apo-transferrin can be combined with other therapies to treat brain stroke patients (See ‘409, [0034]). Examples of suitable therapies to be combined with apo-transferrin include thrombolytic agents, surgical intervention, treatment with citicoline, chelating agents, antioxidant agents, excitotoxic damage limiters, anti-inflammatory agents, treatment with fluoxetine, and lactoferrin (See ‘409, [0034]). However, ‘409 does not expressly teach that the therapy to combine with apo-transferrin is alpha-1 antitrypsin (AAT).
Moldthan et al. teaches that AAT is an endogenous inhibitor of serine proteinases and a primary acute phase protein with potent anti-inflammatory, anti-apoptotic, antimicrobial and cytoprotective activities that could be beneficial in stroke (See Moldthan, abstract; pg. 2, 4th paragraph). Given these properties, Moldthan et al. examined whether AAT could improve ischemic stroke outcome in an established rat model (See Moldthan, abstract; pg. 2, 4th paragraph). Moldthan et al. found that the infarct volumes of the human AAT treatment groups were statistically significantly reduced by 83% and 63% compared with control rats (See Moldthan, abstract). AAT also significantly limited sensory motor systems deficits (See Moldthan, abstract). Thus, Moldthan et al. concludes that human AAT could be a potential therapeutic drug for the protection against neurodegeneration following ischemic stroke (See Moldthan, abstract). Therefore, Moldthan et al. suggests AAT as an anti-inflammatory agent useful to treat ischemic stroke in a patient.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application and modify the teachings of ‘409 and substitute AAT as an anti-inflammatory agent to be co-administered with a therapeutically effective amount of apo-transferrin to a patient in order to treat ischemic stroke by necessarily promoting and/or inducing generation of new neural cells and/or stimulating neural cell development. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because administering AAT was known to treat ischemic stroke in a patient by significantly reducing infarct volume and significantly limiting sensory motor systems deficits as taught by Moldthan et al. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that a therapeutically effective amount apo-transferrin of ‘409 were co-administered with an additional therapy such as an anti-inflammatory agent to a patient to treat ischemic stroke, and therefore, substituting AAT as the inflammatory agent would support the treatment of ischemic stroke in a patient by constituting simple substitution of one known element for another to obtain predictable results and/or some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention pursuant to KSR.
Additionally and/or alternatively, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant application and combine the teachings of ‘409 and Moldthan et al. and administer to a patient a therapeutically effective amount of apo-transferrin in combination with AAT as an anti-inflammatory agent in order to treat ischemic stroke in the patient. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because administering a therapeutically effective amount of apo-transferrin to a patient was known to treat ischemic stroke as taught by ‘409; and because administering AAT to a patient was known to treat ischemic stroke as taught by Moldthan et al. One of ordinary skill in the art at the time the invention was made would have had a reasonable expectation of success given that the therapeutically effective amount of apo-transferrin of ‘409 and the AAT of Moldthan et al. was administered to a patient to treat ischemic stroke. Therefore, "it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose… [T]he idea of combining them flows logically from their having been individually taught in the prior art." (MPEP 2144.06). In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from their having been individually taught in prior art. Therefore, since each of the references teach agents that are effective in treating ischemic stroke, it would have been obvious to combine the two agents with the expectation that such a combination would be effective in treating ischemic stroke. Thus, combining them flows logically from their having been individually taught in prior art.
Thus, the invention as a whole is prima facie obvious over the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 8-10, 22-25, 29-31, and 43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 22-28 of copending Application No.18/004,231 (US Publication No. 2023/0263863 A1) (cited in the IDS received on 7/23/24) in view of Gasull Dalmau et al. US Publication No. 2014/0323409 A1 published on October 30, 2014 (hereinafter referred to as ‘409), Balch et al., J. Stroke 22:159-172 (May 2020), and Moldthan et al., J. Stroke Cerebrovasc. Dis. 23:e355-e363 (2014).
‘231 claims:
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(See ‘231 claims 1 and 22). ‘231’s claims 2-4 and 23-25 are identical to instant claims 2-4 and 23-25 thereby encompassing apo-transferrin. As such, the ‘231 claimed invention is similar to the instantly claimed invention except for with respect where the neurodegenerative event arising from, e.g., NTBI. However, ‘231 claims 1 and 22 broadly encompass any neurodegenerative event. Please see discussion of ‘409 supra. Briefly, ‘409 teaches administering a therapeutically effective amount of apo-transferrin in order to treat a patient who has suffered an ischemic stroke by reducing the neuronal cell damage. Therefore, an ordinary skilled artisan would be motivated with a reasonable expectation of success to administer a therapeutically effective amount of the ‘231 apo-transferrin to a patient that has suffered an ischemic stroke as the neurodegenerative event. It is further noted that neurogenic muscular atrophies (i.e., a species of neurodegenerative disease in ‘231 claim 8) are known to arise from a NTBI such as ischemic stroke as taught by Balch et al. (See Balch, Figure 1; pg. 166, col. 2, last paragraph to pg. 167, col. 2, 4th paragraph). Thus, there is overlap between the ‘231 and instantly claimed inventions.
However, ‘231 does not claim where the apo-transferrin is co-administered with AAT as recited in instant claims 10, 31, and 43.
As discussed supra, ‘409 teaches that apo-transferrin can be co-administered with a second agent such as an anti-inflammatory agent. Moldthan et al. teaches that AAT is an anti-inflammatory agent useful in treating patients who have suffered an ischemic stroke. Therefore, for the reasons set forth in the 103 rejection supra, an ordinary skilled artisan would be motivated with a reasonable expectation of success to co-administer the ‘409 apo-transferrin with AAT to a patient that has suffered an ischemic stroke in order to treat the ischemic stroke by promoting and/or inducing generation of new neural cells and/or stimulating neural cell development in the patient given that both agents are known to treat ischemic stroke. Thus, the ‘231 claimed invention is not patentably distinct from the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 8-10, 22-25, 29-31, and 43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-13, 15-17, 19, 21-22, 25, 45, and 64-65 of copending Application No. 18/548,545 (US Publication No. 2024/0166724 A1) in view of
‘545 claims:
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(See ‘545 claims 1, 4, and 7-9). As such, the ‘545 claimed invention reads on a combination therapy of apo-transferrin and AAT that are administered to a patient in order to treat a neurodegenerative event (i.e., same as ‘545’s neural cell injury) arising from a NTBI caused by an ischemic stroke.
Regarding promoting and/or inducing generation of new neural cells as recited in claim 1 and stimulating neural cell development as recited in claim 22, ‘545 expressly claims treatment of the same patient population, i.e., a patient that suffered a neurodegenerative event arising from a NTBI such as an ischemic stroke, by performing the same manipulative step, i.e., administering a therapeutically effective amount of a transferrin in combination with AAT to the patient, the result oriented effect of promoting and/or inducing generation of neural cells as recited in instant claim 1 or stimulating neural cell development as recited in instant claim 22 would necessarily and inherently occur as a result of practicing the method of ‘545. Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). Therefore, the ‘545 anticipates the limitations as recited in instant claims 1-2, 8-10, 22-23, 29-31, and 43.
However, ‘545 does not expressly claim where the transferrin is human or recombinantly produced as recited in instant claims 3-4 and 24-25.
Please see discussion of ‘409 supra teaching that the apo-transferrin for its use in the present invention is preferably human apo-transferrin (See ‘409, [0017], [0041]). ‘409 discloses that the apo-transferrin can be prepared by methods known in the state of the art (See ‘409, [0041]). Moreover, ‘409 discloses that the apo-transferrin is in a recombinant form (See ‘409, [0041]). Therefore, an ordinary skilled artisan would be motivated with a reasonable expectation of success to co-administer AAT and human recombinant apo-transferrin to a patient in order to treat a neurodegenerative event (i.e., same as ‘545’s neural cell injury) arising from a NTBI caused by an ischemic stroke given that transferrin is well-known to derived from human and produced recombinantly.
Thus, the ‘545 claimed invention is not patentably distinct from the instantly claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-4, 8-10, 22-25, 29-31, and 43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of US RE49,129 E in view of Gasull Dalmau et al. US Publication No. 2014/0323409 A1 published on October 30, 2014 (hereinafter referred to as ‘409) and Moldthan et al., J. Stroke Cerebrovasc. Dis. 23:e355-e363 (2014).
‘129 claims:
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(See ‘129 claims 1, 9, and 11). As such, the ‘129 claimed invention encompasses administering a therapeutically effective amount of a transferrin with a iron saturation that overlaps with the instant percentage of 20% or less to a patient in order to treat a HIF-related pathological condition where the condition is associated with ischemia (See ‘129 claim 8) and where the ischemia is due to stroke. Thus, the ‘129 claimed invention reads on the instant patient population, i.e., a patient that has suffered a neurodegenerative event arising from a NTBI caused by an ischemic stroke, and the instant manipulative step, i.e., administering a therapeutically effective amount of a transferrin with an iron saturation that overlaps with the instant percentage of 20% or less. Therefore, the result oriented effect of promoting and/or inducing generation of neural cells as recited in instant claim 1 or stimulating neural cell development as recited in instant claim 22 would necessarily and inherently occur as a result of practicing the method of ‘129. Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). Therefore, the ‘129 anticipates the limitations as recited in instant claims 1-2, 4, 8-9, 22-23, 25, and 29-30.
However, ‘129 does not expressly claim where the transferrin is human as recited in instant claims 3 and 24, and does not expressly claim where the transferrin is co-administered with AAT as recited in instant claims 10, 31, and 43.
Regarding claims 3 and 24, please see discussion of ‘409 supra teaching that the apo-transferrin for its use in the present invention is preferably human apo-transferrin (See ‘409, [0017], [0041]). Therefore, an ordinary skilled artisan would be motivated with a reasonable expectation of success to administer human recombinant apo-transferrin to a patient in order to treat a HIF-related pathological condition associated with ischemic stroke given that transferrin is well-known to derived from human.
Regarding claims 10, 31, and 43, as discussed supra, ‘409 teaches that apo-transferrin can be co-administered with a second agent such as an anti-inflammatory agent. Moldthan et al. teaches that AAT is an anti-inflammatory agent useful in treating patients who have suffered an ischemic stroke. Therefore, for the reasons set forth in the 103 rejection supra, an ordinary skilled artisan would be motivated with a reasonable expectation of success to co-administer the ‘409 apo-transferrin with AAT to a patient that has suffered an ischemic stroke in order to treat the ischemic stroke by promoting and/or inducing generation of new neural cells and/or stimulating neural cell development in the patient given that both agents are known to treat ischemic stroke. Thus, the ‘129 claimed invention is not patentably distinct from the instantly claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THEA D' AMBROSIO whose telephone number is (571)270-1216. The examiner can normally be reached M-F 11:00 to 8:00 pm.
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654