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. The amendment received on July 24, 2026, canceled claims 2 and 23; and amended claims 1 and 22.
Claims 1, 3-10, 22, 24-31, and 43 are currently pending and claims 1, 3-4, 8-10, 22, 24-25, 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.
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, with respect to the structure of the claimed protein, it 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. With respect to required functional/physical properties, the claimed protein must exhibit the property of iron saturation of less than 20%.
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), but the claimed is limited to neuronal cells. Thus, the definition of a neurodegenerative event would pertain to an event that causes the loss of structure and/or function of neuronal cells and includes the death of neuronal cells. 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). Note: that Applicant elected an ischemic stroke as the NTBI cause. Thus, examination of claim 1 is limited to developing new neuronal cells by neurogenesis 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.
For claim 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).
Response to Arguments
Applicant’s arguments, see Response, filed 7/24/26, with respect to the 112(a), scope of enablement, rejection have been fully considered and are persuasive. The rejection of claims 1-4, 8-10, 22-25, 29-31, and 43 as failing the scope of enablement requirement has been withdrawn.
Applicant’s arguments, see Response, filed 7/24/26, with respect to the 102(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 1-4, 8-9, 22-25, 29, and 43 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/ has been withdrawn.
Maintained/Modified Rejections in light of Applicants’ Amendments
Claim Rejections – 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-4, 8-10, 22, 24-25, 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. Please note that the rejection has been updated in light of Applicants’ amendments.
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, with respect to the encompassed structure of the claimed protein, it 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. 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 AND exhibit the physical property of having an iron saturation of less than 20%. Thus, the scope of the claimed proteins encompass an enormous structural 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 AND have an iron saturation of less than 20%.
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. As such, ‘409 fails to provide any indication of a necessary core structure/sequence to ensure the amino acid sequence of the transferrin exhibits an iron saturation of less than 20% excluding that of apo-transferrin, which has a 0% iron saturation. Moreover, 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). However, there is no indication that the iron saturation level for either of the monoferric hTF mutants. Plus, 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 including its ability to bind/interact with iron. 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). It is noted that the SEQ ID NOs: 4-5 mutants are the same species taught by Steele et al. as described supra for the monoferric hTF mutants. 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. Plus, Example 3 demonstrates that apoTF and holoTF (each SEQ ID NO: 1) and N-lobe mutant TF (i.e., SEQ ID NO: 4) induced neurogenesis of SH-SY5Y cells even though ApoTF and the N-mut TF exhibit reduced iron binding thereby suggestive that iron-binding is not the sole mechanism of action for neurogenic potential of ApoTF (See instant, 30, 2nd paragraph; Figure 3B). Example 6 examined the role of iron saturation in transferrin efficacy in 4 species of ApoTFs with different iron saturation levels relative to the holoTF (See instant, pg. 33, 2nd paragraph; Table 1). The iron saturation is only indicated for three of the four ApoTFs, i.e., 27%, 59%, and 24% for ApoTF A, B, and C, respectively (See instant, Table 1). It is presumed that each has the identical amino acid sequence to SEQ ID NO: 1. Moreover, Figure 6B refers to ApoTFs with iron saturation levels of less than 0.3%, 2%, 5%, 10%, 20%, 30%, and 50% (See instant, Figure 6B). The various iron saturation levels were generated by mixing ApoTF with HoloTF, but there is no indication what concentration or ratio is needed to achieve these saturation levels, especially given that the iron saturation level being 20% or less improves neuronal fold change. As such, the instant specification teaches the wild-type recombinant TF that is fully saturated and the natural ApoTF with less than 1% iron saturation, each with the sequence of SEQ ID NO: 1, three apoTFs with the same sequence but different iron saturation levels, and three mutants (i.e., SEQ ID NOs: 3-5), but does not identify the iron saturation level of any of the mutants. It further is noted that in order to obtain a transferrin that exhibits an iron saturation of less than 20%, the specification only provides examples of a mixture of holoTF and apoTF in ratios/amounts that result in various iron saturation levels. Thus, 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. Therefore, 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, 3-4, 8-10, 22, 24-25, 29-31, and 43 do not meet the written description requirement.
Response to Arguments
Applicant’s arguments filed 7/24/26 for claims 1, 3-4, 8-10, 22, 24-25, 29-31, and 43 as failing the written description requirement have been fully considered but they are not persuasive.
In response to Applicants’ first, second, and fifth arguments, i.e., (1) the claimed proteins are limited to a recognized structural family such as transferrin and lactoferrin that share 61% sequence identity, both exhibit a highly conserved 3D-structure and both possess analogous iron-binding domains (N- and C-lobes); (2) the specification explicitly limits variants to those preserving structure such that in the variants the substitutions must not “materially alter the structure or hydropathic nature” where the variants may retain high sequence homology, e.g., 90-99%, and thus, the claimed variants are those that are inherently structurally constrained by being able to promote neurogenesis; and (5) one or skill in the art would recognize which variants fall within the structural class and which modifications preserve function given that transferrin and lactoferrin are well-characterized proteins with their structure, domains and functional regions known, and where conservative substitutions are routinely understood to preserve function (See Applicant’s Response received on 7/24/26, pg. 10), they are found unpersuasive. MPEP §2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Additionally, the importance of structure/function correlations was highlighted by the courts (Abbvie Deutschland v. Janssen Biotech and Centorcor Biologics, App. No. 2013-1338, -1346 (Fed. Cir. , July 1, 2014)). The Abbvie case involved antibodies and written description. The court stated: “We have held that “a sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. At 1350 (quoting Eli Lilly, 119 F.3d at 1568– 69).”. The courts then further stated: “With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” (emphasis added) and then state: “ Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). However, the record here does not indicate such an established correlation. Instead, Abbvie used a trial and error approach to modify individual amino acids in order to improve the IL-12 binding affinity. Moreover, the ’128 and ’485 patents do not describe any common structural features of the claimed antibodies. The asserted claims attempt to claim every fully human IL-12 antibody that would achieve a desired result, i.e., high binding affinity and neutralizing activity, and cover an antibody as different as Stelara, whereas the patents do not describe representative examples to support the full scope of the claims.”
In the instant case, it is acknowledged that the wild-type transferrin protein is well-characterized as discussed by ‘704 and Steele et al. However, the scope of the claimed transferrin is NOT limited to the wild-type protein. As stated in the “Claim Interpretation” section and rejection supra, the claimed transferrin protein is defined 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). As such, the structural scope of the claimed transferrin protein is NOT limited to the wild-type transferrin amino acid sequence. Rather, the claimed transferrin protein encompasses an enormous number of mutants (one or more substitutions and/or insertions) and/or fragments (one or more deletions) and/or derivatives of the full length transferrin protein, which is 576 amino acids in length, as noted in the rejection. Thus, the structural breadth of the claimed transferrin protein is enormous because (1) there is no core structure/sequence required that each species within the claimed genus would share in order for the species to be functionally similar to the wild-type protein and to have an iron saturation level less than 20%, and/or (2) there is a lack of a representative number of species known in the art and/or disclosed in the specification that an ordinary skilled artisan would be able to extrapolate the positive data from to extend to the scope of the claimed genus. Attempting to limit structure by reciting function such that the modifications may not materially alter the structure or hydropathic nature of the modified protein relative to the wild-type protein does not provide any guidance as to what structure may or may not materially alter the structure or hydropathic nature. And even if it did, “may” not materially alter the structure or hydropathic nature of the protein relative to the wild-type protein is NOT a required functional limitation. “May” is analogous to “optional” or “can” or “could”, i.e., the modification could or could not materially alter the structure or hydropathic nature of the protein relative to the wild-type protein. Thus, even if such function was limiting in nature, it is not a required limitation, whether in the definition or recited in the claimed invention. Therefore, in the instant case, as was the case in Abbvie, there is insufficient evidence that there is an established structure/function correlation in the art and/or the instant specification in light of the breadth of the claimed genus of transferrin proteins.
Regarding Applicant’s assertion that the claimed proteins are limited to a recognized structural family, i.e., homologues, it is noted that the features upon which applicant relies (i.e., claimed proteins are limited are limited to a recognized structural family) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). However, even if the claimed invention recited that the transferrin to be administered is a protein belonging to the same recognized structural family, the written description requirement would not be met. Although not expressly referred to as homologues, such a term is relevant as to what proteins would be encompassed by Applicants “recognized structural family.” Homology is defined as similarity in structure, physiology, or development species or organisms based upon their descent from a common evolutionary ancestor (See “Homology”, Encyclopedia Britannica, available online at www.britannica.com/print/article/270557, 2 pages at pg. 1, 1st paragraph (accessed on 7/22/18)). Pearson et al. similarly defines homology based on similarity and based upon a common evolutionary ancestor but takes the analysis further. In particular, Pearson et al. teaches that the concept of homology, common evolutionary ancestry, is central to computational analyses of protein and DNA sequences, but the link between similarity and homology is often misunderstood (See Pearson et al., Curr. Protoc. Bioinformatics, 9 pages (2013) at pg. 2, 2nd paragraph). Thus, Pearson et al. infers homology when two sequences or structures share more similarity than would be expected by chance; when excess similarity is observed, the simplest explanation for that excess is that the two sequences did not arise independently, they arose from a common ancestor (See Pearson article, pg. 2, 2nd paragraph). However, Pearson et al. further teaches that when a similarity search finds a statistically significant match, it can be confidently inferred that the two sequences are homologous, but if no statistically significant match is found in a database, it is not certain that no homologs are present (See Pearson article, pg. 2, 3rd paragraph). Moreover, Pearson et al. teaches that the relationship between homology and function is less predictable because a single protein structure can have multiple functions and because the concept of function is more ambiguous (See Pearson article, pg. 5, 3rd paragraph). Importantly, Pearson et al. teaches that when conducting protein sequence searches the 30% identity rule-of-thumb is too conservative; statistically significant protein homologs can share less than 20% identity (See Pearson article, pg. 7, 3rd full paragraph).
Additionally, Kanduc teaches that homology pertains to comparative studies indicating an ancient common origin and temporal evolution and refers to structural characteristics (See Kanduc, J. Pept. Sci. 18:487-494 (2012) at pg. 488, col. 1, 2nd paragraph) whereas similarity is a quantitative property (See Kanduc article, pg. 488, col. 1, last full paragraph). In comparative protein biochemistry, homology retains the original meaning of having a common evolutionary origin and is used to evolutionarily define two or more proteins by locating common structural characteristics and common spatial distribution of, for instance, beta strands, helices, and folds (See Kanduc article, pg. 488, col. 1, 2nd paragraph). Measuring structural homology involves computing the geometric-topological features of a space (See Kanduc article, pg. 488, col. 1, 2nd paragraph). Nonetheless, Kanduc teaches that it is important to note that homologous structures do not imply sequence similarity as a necessary condition as demonstrated in Figure 1 where two sequences are characterized by a highly comparable spatial structure but the pairwise sequence alignments shows little sequence similarity (See Kanduc article, pg. 488, col. 1, 3rd paragraph; Figure 1).
Furthermore, a professor at Stanford University stated the difference between sequence homology, similarity, and identity depends on the context where there are different opinions as to what the terms infer (See Samudrala, R., “Difference Between Homology, Identity, and Similarity,” available online at http://www.bio.net/mm/proteins/1998-July/006538.html, 1 page (1998) at 1st and 2nd paragraphs), but as long as it is clear from the context or from an explicit statement what is meant, that is all that is necessary (See Samudrala reference, last paragraph). Thus, the prior art demonstrates that although highly similar sequences constitute homologous sequences, homologous sequences are not limited to sequences that are highly similar or identical, but encompasses a broader scope of sequences. Here, even if the claimed transferrin protein was limited to any proteins within the same structural family, such a family encompasses any compound/peptide that shares a common ancestor with the full-length wild-type transferrin structure/sequence but is not limited to similar amino acid content or similar structure. Moreover, a single species of homologue, i.e., wild-type apo-lactoferrin (See instant, pg. 31, 3rd paragraph), does not constitute a representative number of proteins that fall within the proposed transferrin structural family; especially since the same structural protein, i.e., holoTF except fully saturated with iron, was unable to induce neuronal differentiation (See instant, pg. 31, 2nd paragraph). Knowledge of the structure and function of the natural wild-type apo-TF does not support what modifications to the wild-type apoTF could be made while retaining such function. Therefore, the Examiner maintains that because there is no identified core structure/sequence taught in the art and/or in the instant specification that would be necessary for each species within the claimed genus to contain in order to function similar to the wild-type transferrin and exhibit an iron saturation level less than 20%, an ordinary skilled artisan would not put Applicants in possession of the breadth of the claimed genus.
In response to Applicant’s third argument, i.e., the specification provides multiple representative species of SEQ ID NOs: 1 and 3-5 TF that demonstrate that the neurogenic activity of apoTF is maintained in the mutants with altered iron binding and where the mutants have equivalent or similar function despite structural variation (See Applicant’s Response received on 7/24/26, pg. 9), it is found unpersuasive. As discussed in the rejection above and pursuant to MPEP 2163.05(I)(B), [t]he written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) (Claims directed to PTFE dental floss with a friction-enhancing coating were not supported by a disclosure of a microcrystalline wax coating where there was no evidence in the disclosure or anywhere else in the record showing applicant conveyed that any other coating was suitable for a PTFE dental floss). In the instant case, it is noted that the art teaches a minimal number of species within the claimed genus where specific residues are essential for transferrin function, i.e., residues D356, E367, and K511 of the wild-type transferrin, for hTF functionality. Similarly, it is acknowledged that the instant specification teaches three specific mutants of transferrin, i.e., SEQ ID NOs: 3-5. However, it is not readily apparent from the prior art or the instant specification if these TF mutant sequences even have an iron saturation level less than 20%. As discussed in the rejection supra, the instant specification indicates three apoTF sequences in Table 1, all of which had iron saturation levels above 20%. However, it is not clear whether these three apoTF sequences correspond to SEQ ID NOs: 3-5. Besides the natural wild-type apoTF, Applicants only achieved various iron saturation levels of transferrins by mixing the wild-type apoTF and holoTF is various ratios, and notably, undisclosed ratios. As such, although the instant specification teaches SEQ ID NO: 1 as the wild-type TF sequence that has an iron saturation level of less than 1% as exhibiting the claimed function, there is insufficient guidance provided with respect to whether the three specific TF mutants that have either 1 or 2 specific substitutions would function as claimed and with respect to the necessary ratio needed between apoTF and holoTF to achieve an iron saturation of less than 20%. Thus, the Examiner maintains that a determination of a core structure, sequence or residues that would be necessary in order for a transferrin protein as claimed to function similar to the wild-type transferrin protein and have an iron saturation level of less than 20% in order to develop new neuronal cells by neurogenesis, is not apparent. Without such a determination, it would be difficult for a skilled artisan to envision the correlation between structure and function for the whole genus and/or to predict what would be covered by the functionally claimed genus because Applicants have failed to provide a representative number of species to support the scope of the whole genus.
In response to Applicant’s fourth argument, i.e., the invention identifies that the iron-binding state is a key mechanistic determinant of neurogenesis where apoTF (low iron saturation) has neurogenic activity and holoTF (high iron saturation) has no to little neurogenic activity thereby demonstrating a clear structural-functional link (See Applicant’s Response received on 7/24/26, pg. 9-10), it is found unpersuasive. In the instant case, although there are situations where a single species adequately supports a genus (See MPEP 2163.05(I)(B), e.g., In re Rasmussen, 650 F.2d 1212, 1214, 211 USPQ 323, 326-27 (CCPA 1981) (disclosure of a single method of adheringly applying one layer to another was sufficient to support a generic claim to “adheringly applying” because one skilled in the art reading the specification would understand that it is unimportant how the layers are adhered, so long as they are adhered), given that there are only two specific species (i.e., wild-type apoTF and apoLF) that exhibit the function of the wild-type apoTF and have an iron saturation level of less than 20%, the evidence in the art and specification indicate ordinary skilled artisan could not predict the operability in the invention of any species other than the two disclosed. Even assuming arguendo that SEQ ID NOs: 3-5 have an iron saturation level below 20%, the five specific species of TFs do not constitute a representative number of species given the breadth of the claimed genus. Therefore, even if the instant specification is deemed to support possession of a limited number of TFs, Applicants have not demonstrated a representative number of species within the claimed genus of TFs that encompass mutants, derivatives, and fragments to constitute possession of the claimed genus.
Accordingly, the rejection of claims 1, 3-4, 8-10, 22, 24-25, 29-31, and 43 is maintained.
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, 3-4, 8-9, 22, 24-25, 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/. Please note that the rejection has been updated in light of Applicants’ amendments.
For claims 1, 8-9, 22, 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 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 1, 8-9, 22, and 29-30.
Regarding developing of new neuronal cells by neurogenesis 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 where the transferrin has an iron saturation of less than 20%, the result oriented effect of developing of new neuronal cells by neurogenesis 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, 8-9, 22, 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, 3-4, 8-9, 22, 24-25, 29, and 43.
Response to Arguments
Applicant's arguments filed 7/24/26 for claims 1, 3-4, 8-9, 22, 24-25, 29, and 43 as being anticipated by ‘409 have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s first argument, i.e., the ‘409 reference is directed to the treatment of brain stroke to reduce the damage caused after a brain stroke, meaning to protect the still living neural cells and limit the consequences of the brain stroke, i.e., neuroprotection, as is evident from the examples in ‘409 that administer apoTF directly after, 50 minutes after, or about 100 minutes after provoking ischemia whereas the instant invention is directed to a further medical use of generating new neuronal cells leading to brain tissue regeneration after neuronal death and subsequent recovery of lost function due to a brain stroke, i.e., neurogenesis (See Applicant’s Response received on 7/24/26, pg. 10-13), it is found unpersuasive. Pursuant to MPEP 2112.02(I), under the principles of inherency, if a prior art device, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art device. When the prior art device is the same as a device described in the specification for carrying out the claimed method, it can be assumed the device will inherently perform the claimed process. In re King, 801 F.2d 1324, 231 USPQ 136 (Fed. Cir. 1986). See also Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993) (The Board rejected a claim directed to a method for protecting a plant from plant pathogenic nematodes by inoculating the plant with a nematode inhibiting strain of P. cepacia. A U.S. patent to Dart disclosed inoculation using P. cepacia type Wisconsin 526 bacteria for protecting the plant from fungal disease. Dart was silent as to nematode inhibition but the Board concluded that nematode inhibition was an inherent property of the bacteria). Moreover, pursuant to MPEP 2112.02(II), the discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the "use" is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds, as well as a method of using them for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the inventors had merely found a new property of the compound and such a discovery did not constitute a new use) (emphasis added).
In the instant case, it is acknowledged that ‘409 focuses on neuroprotection and reducing damage caused after a brain stroke by administering an effective amount, i.e., a dose between 1 and 1000 mg/kg weight, of apoTF, i.e., defined as being iron-free thereby constituting a specific TF species that has a iron saturation level within the claimed range of less than 20%, to an animal who has suffered a brain ischemic stroke. It is not disputed that there is a distinction between neuroprotection and neurogenesis. However, the rejection supra is not based on ‘409 expressly disclosing treating brain ischemic stroke in an animal by inducing neurogenesis and stimulating neural cell development. Rather, as stated in the rejection supra, the rejection is based on ‘409 inherently disclosing treating brain ischemic stroke in an animal by inducing neurogenesis and stimulating neural cell development. The rejection indicates that ‘409 discloses a specific embodiment of using the instantly claimed manipulative step, which includes administering the identical transferrin, i.e., apoTF that has an iron saturation level of 0%, in an effective amount, to the instantly claimed patient population, i.e., a patient that has suffered a neurodegenerative event arising from a non-traumatic brain injury, i.e., an ischemic stroke (See instant claims 1, 8-9, 22, and 29-30). As such, the ‘409 disclosure expressly reads on the instant manipulative step and instant patient population. The question is then whether the instantly claimed intended use, i.e., developing new neuronal cells via neurogenesis and stimulating neural cell development, is inherently disclosed by the ‘409 disclosure. The Examiner maintains that the answer to this question is yes.
Here, analogous to the fact patterns in Ex parte Novitski and In re May, the Examiner maintains that inducing neurogenesis and stimulating neural cell development constitutes a previously undisclosed or unrecognized property of the claimed manipulative step including the administered apoTF, and thus, does not constitute a new medical use as asserted by Applicant. The fact that ‘409 recognizes or identifies neuroprotection as the means of treating a brain ischemic stroke in an animal does not per se preclude that inducing neurogenesis and stimulating neural cell development is not also occurring simultaneously. As acknowledged by Applicant, ‘409 expressly discloses administering apoTF in an effective amount directly after inducing ischemia, 50 minutes after inducing ischemia, and after about 100 minutes after inducing ischemia. However, contrary to Applicant’s argument, neuronal cell death would necessarily have occurred following the ischemic induction. Hassan et al. teaches stroke is a medical emergency where millions of neurons are lost with every minute of stroke (See Hassan et al., MJAFI 65:62-65 (2009) at pg. 62, col. 1, 1st paragraph). Following an acute ischemic stroke and without treatment 4 million neurons, 12 million brain cells, and 15 billion synapses die every minute (See Hasan, pg. 62, col. 1, 1st paragraph). Similarly, Ju et al. teaches that if cerebral blood flow is interrupted, then neuronal metabolism can be effected within 30 seconds and will completely stop within 2 minutes of deprivation (See Ju et al., “3.2. Stroke and Loss of Blood Flow as an Acute Injury to the Brain,” in: Neuroscience, 3rd Ed., 8 pages (2021) at pg. 2, 2nd paragraph). If left unchecked, neuronal cell death occurs in 5 minutes (See Ju, pg. 2, 2nd paragraph). As such, the animals in the experiments performed by ‘409 would have inherently experienced neuronal cell death; especially when an effective amount of apoTF is administered 50 minutes or about 100 minutes after inducing ischemia. Thus, contrary to Applicant’s argument, the experiments described in ‘409 that induce a brain stroke would necessarily include neuronal cell death. Therefore, contrary to Applicant’s argument, although ‘409 does not expressly disclose treating a brain ischemic stroke in a patient by administering an effective amount of apoTF to the patient in need thereof by inducing neurogenesis and stimulating neural cell development, the ‘409 disclosure inherently discloses such a method given that the mechanism by which the brain ischemic stroke is treated in ‘409’s patient is an inherent result of property dependent upon the instantly claimed manipulative step and instantly claimed patient population.
In response to Applicant’s second argument, i.e., amended claim 1 is directed to specific injuries characterized by progressive neuronal cell death, which enables to treat a new subgroup of patients thereby leading to a true new clinical situation (See Applicant’s Response received on 7/24/26, pg. 14), it is found unpersuasive. It is noted that the features upon which applicant relies (i.e., specific injuries characterized by progressive neuronal cell death) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In the instant case, assuming arguendo, that there are distinct patient populations that suffer a brain ischemic stroke, i.e., one that has injuries characterized by progressive neuronal cell death and another that only requires neuroprotection prior to death of a neuron, the scope of the claimed methods do not include a distinction in the claimed patient population. Rather, the claimed patient population has suffered a neurodegenerative event arising from a brain ischemic stroke thereby encompassing any patient irrespective of whether the patient has incurred neuronal cell death. However, even if the claimed methods recite that the patient suffered a brain ischemic stroke resulting in neuronal cell death, as discussed supra, a patient suffers neuronal cell death within minutes of an ischemic stroke. Since the animals in ‘409’s experiments were not administered apoTF until 50 or about 100 minutes after ischemic stroke, the animals would have suffered from neuronal cell death. Thus, contrary to Applicant’s argument, the instant methods are not directed to a new subgroup of patients, but rather represents a previously unidentified mechanism by which the administration of an effective amount of apoTF treats a patient who has suffered a brain ischemic stroke.
In response to Applicant’s third argument, i.e., it must be considered that numerous compounds have been shown to exert neuroprotective effects without promoting neurogenesis such as N-acetylcysteine (NAC) and various polyphenols (See Applicant’s Response received on 7/24/26, pg. 14), it is found unpersuasive. Applicant has not provided any evidence to support this argument. Thus, this argument is merely the argument of counsel and is unsupported by evidence or declarations of those skilled in the art. Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See M.P.E.P. § 2129 and § 2144.03 for a discussion of admissions as prior art. Counsel's arguments cannot take the place of objective evidence. In re Schulze, 145 USPQ 716 (CCPA 1965); In re Cole, 140 USPQ 230 (CCPA 1964); and especially In re Langer, 183 USPQ 288 (CCPA 1974). See M.P.E.P. § 716.01(c) for examples of attorney statements that are not evidence and that must be supported by an appropriate affidavit or declaration. Furthermore, it is noted that a lack of evidence of inducing neural stem cell proliferation or differentiation, does not per se correlate to where these other known compounds do not or cannot induce neural cell development. Plus, the functionality of unrelated compounds does not impact whether the instant transferrin exhibits the claimed intended use, especially, given the ‘409 disclosure. Therefore, contrary to Applicant’s argument, the efficacy of unrelated compounds, even if evidence is provided, is not dispositive as to whether the instant transferrin inherently exhibits the claimed intended use.
Accordingly, the rejection of claims 1, 3-4, 8-9, 22, 24-25, 29, and 43 is maintained as Applicants’ arguments are found unpersuasive.
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.
Response to Arguments
Applicant's arguments filed 7/24/26 for claims 1, 10, 22, and 31 as being unpatentable pursuant under 35 USC 103(a) have been fully considered but they are not persuasive. It is noted that Applicants’ arguments pertain to the Moldthan reference failing to overcome the deficiency of the ‘409 reference as discussed supra for the 102(a)(1). Since the response to the arguments would mirror the response for the 102 rejection supra, the response will not be reiterated but is incorporated herewith.
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, 3-4, 8-10, 22, 24-25, 29-31, and 43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 22, and 24-28 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). Please note the rejection has been updated in light of Applicants’ amendments.
‘231 claims:
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(See ‘231 claims 1 and 22). ‘231’s claims 3-4 and 24-25 are identical to instant claims 3-4 and 24-25 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 developing new neuronal cells via neurogenesis 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, 3-4, 8-10, 22, 24-25, 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 Gasull Dalmau et al. US Publication No. 2014/0323409 A1 published on October 30, 2014 (hereinafter referred to as ‘409). Please note the rejection has been updated in light of Applicants’ amendments.
‘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 developing new neuronal cells via neurogenesis 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 developing new neuronal cells via neurogenesis 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, 8-10, 22, 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, 3-4, 8-10, 22, 24-25, 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). Please note the rejection has been updated in light of Applicants’ amendments.
‘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 an 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 developing new neuronal cells via neurogenesis 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, 4, 8-9, 22, 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 developing new neuronal cells via neurogenesis 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.
Response to Arguments
Applicant's arguments filed 7/24/26 for claims 1, 3-4, 8-10, 22, 24-25, 29-31, and 43 as being unpatentable over related co-pending applications have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s argument with respect to the ‘231 co-pending application, it is unclear how the amendments to instant claim 1 are not found in the ‘231 claimed invention. The ‘231 claimed invention expressly encompasses generating new neural cells in a patient who has suffered a neurodegenerative event by administering an effective amount of a transferrin that has an iron saturation level of 20% or less. As such, the amendments added to instant claim 1 are found in the ‘231 claimed invention. Therefore, contrary to Applicant’s argument, the ‘231 claimed invention and the instant invention are not patentably distinct.
In response to Applicant’s argument with respect to the ‘545 co-pending application, it is acknowledged that a co-pending application with a later effective filing date would be overcome IF it is the only remaining rejection. However, the rejection over the ‘545 co-pending application is not the only remaining rejection. Thus, the rejection over the ‘545 co-pending application is maintained.
In response to Applicant’s argument with respect to RE49129E1, it is noted that Applicants’ arguments are similar to their arguments in response to the 102(a)(1) rejection supra. As such, the response to the arguments for the 102 rejection are incorporated herewith. Furthermore, as discussed in the instant rejection supra, the ‘129 claimed invention expressly claims where MCAo is a condition associated with ischemia due to stroke, i.e., a neurodegenerative event arising from a NTBI such as ischemic stroke. Thus, contrary to Applicant’s argument, the ‘129 claimed invention is directed to treating a species of patient population that falls within the claimed genus of patient populations by performing a similar manipulative step where the transferrin administered in ‘129 would have an iron saturation level of 20% or less without evidence to the contrary.
Accordingly, the obviousness-type double patenting rejections are maintained.
Conclusion
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.
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
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